A Randomized, Global, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Once-daily Oral Avatrombopag for the Treatment of Adults With Thrombocytopenia Associated With Liver Disease Prior to an Elective Procedure

At a glance

Drugs Avatrombopag (Primary)
Indications Thrombocytopenia
Focus Registrational; Therapeutic Use
Acronyms ADAPT II
Sponsors Dova Pharmaceuticals; Eisai Inc

Most Recent Events

30 Apr 2020 According to a Dova Pharmaceuticals media release, DOPTELET (avatrombopag) has been granted approval from the China National Medical Products Administration (NMPA) for the treatment of thrombocytopenia in adult patients with chronic liver disease (CLD) who are scheduled to undergo a procedure (i.e., the CLD indication).The approval was based on safety and efficacy data from two global Phase 3, double-blind, placebo-controlled trials (NCT01972529 and NCT01976104).
27 Jun 2019 According to an Dova Pharmaceuticals media release, the company will host a conference call to discuss the approval by FDA.
27 Jun 2019 According to an Dova Pharmaceuticals media release, the U.S. Food and Drug Administration(FDA) has approved a supplemental New Drug Application(sNDA) that expands the use of DOPTELET(avatrombopag) to include the treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Trial Overview

Outcome

Primary endpoint met - positive

Purpose

This phase III study investigated the efficacy of avatrombopag in patients with thrombocytopenia associated with liver disease. Patients were assessed according to mean baseline platelet counts (lower versus higher).

Comments

According to a Sobi North America media release, based on data from ADAPT 1 and ADAPT 2 and other phase 2 and phase 3 studies for chronic ITP, Health Canada has approved avatrombopag, an oral thrombopoietin receptor agonist , for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP)
According to a Dova Pharmaceuticals media release, DOPTELET (avatrombopag) has been granted approval from the China National Medical Products Administration (NMPA) for the treatment of thrombocytopenia in adult patients with chronic liver disease (CLD) who are scheduled to undergo a procedure (i.e., the CLD indication).The approval was based on safety and efficacy data from two global Phase 3, double-blind, placebo-controlled trials (NCT01972529 and NCT01976104) (as of 30th Apr 2020)
The U.S. Food and Drug Administration(FDA) approved a supplemental New Drug Application(sNDA) that expands the use of DOPTELET(avatrombopag) to include the treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment (as of 27th Jun 2019).
Based on the data from ADAPT-1 and ADAPT-2 trials, Doptelet was approved by both the United States Food and Drug Administration (FDA; as of 21st May 2018) and European Medicines Agency (EMA; as of 25th Jun 2019) for treatment of thrombocytopenia (low platelet counts) in adult patients with chronic liver disease (CLD) who are scheduled to undergo a procedure.

Primary Endpoints

Met on 22 Sep 2017

Proportion of participants who do not require a platelet transfusion or any rescue procedure for bleeding after randomization and up to 7 days following an elective procedure

description: To confirm that avatrombopag (60 mg avatrombopag for participants with platelet count less than 40 x 10^9/L and 40 mg avatrombopag for participants with platelet count from 40 to less than 50 x 10^9/L) is superior to placebo in removing the need for platelet transfusions or any rescue procedure for bleeding after randomization and up to 7 days following an elective procedure in participants with chronic liver disease who have thrombocytopenia.
time_frame: Baseline and up to 7 days after day of procedure^[1]

Other Endpoints

Percentage of Participants Who Achieved a Platelet Count Greater Than or Equal to 50 x 10^9/L on Scheduled Procedure Day

description: Responders were defined as participants who achieved a platelet count greater than or equal to 50 x 10^9/L on the procedure day. Participants missing a platelet count on the procedure day were conservatively considered as not achieving a platelet count of 50x10^9/L in the analysis, (i.e. Non-responders). time_frame: Day 10 to Day 13 (Visit 4)

Change From Baseline in Platelet Counts on Scheduled Procedure Day

description: Last observation carried forward was used for participants with a missing platelet count on the scheduled procedure day. Platelet count was measured preprocedure and before any platelet transfusion. time_frame: Baseline (Visit 2) to Procedure Day 10 to Day 13 (Visit 4)

Percentage of Participants With a World Health Organization (WHO) Bleeding Score Greater Than or Equal to 2 After Randomization and up to 7 Days After an Scheduled Procedure

description: The severity of bleeding events was assessed by the investigator (or appropriately delegated study site personnel) using the WHO bleeding scale. The WHO bleeding scale is a clinical investigator-assessed five-point scale with Grade 0 = No bleeding, Grade 1 = Petechial bleeding, Grade 2 = Mild blood loss (clinically significant), Grade 3 = Gross blood loss requires transfusion (severe), and Grade 4 = Debilitating blood loss, retinal or cerebral associated with fatality. Participants with missing information are considered as having a WHO bleeding score greater than or equal to 2 in the analysis. time_frame: Baseline (Visit 2) up to 7 days post scheduled procedure

Number of Participants Experiencing an Adverse Event

description: Safety assessments consisted of monitoring and recording all adverse events (AEs) and serious adverse events, including platelet transfusion-related complications; routine laboratory evaluation for hematology, serum chemistry, and urine values; periodic measurement of vital signs and electrocardiograms (ECGs); the performance of physical examinations; and Doppler sonography. AE severity was graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death related to the AE. All AEs graded as 4 or 5 were considered to be serious. Treatment-emergent adverse events (TEAEs) were defined as an AE that started on or after the date of first dose of study drug, up to 30 days after the last dose of study drug. Treatment-related AEs were considered by the investigator to be possibly or probably related to study drug. time_frame: From date of first dose of study drug up to 30 days after the last dose of study drug, up to approximately 3 years and 2 months^[2]

Diseases Treated

Indication	Qualifiers	Patient Segments
Thrombocytopenia	treatment	-

Biomarker

NCT Number	Biomarker Function
NCT01976104	AT-III	Eligibility Criteria
	Factor V	Eligibility Criteria
	Prothrombin (PT)	Eligibility Criteria

For more detail, check out BiomarkerBase: the leading source of information about biomarkers used in drug development and diagnostic tests, tracking a comprehensive list of biomarker uses worldwide by over 800 companies

Subjects

Subject Type patients
Number
Planned: 300

Actual: 204
Sex male & female
Age Group ≥ 18 years; adult

Patient Inclusion Criteria

Inclusion Criteria 1. Participants greater than or equal to 18 years of age at Screening with chronic liver disease 2. Participants who have a mean baseline platelet count of less than 50 x 10^9/L. Platelet counts must be measured on 2 separate occasions, during the Screening Period and at Baseline, and must be performed at least one day apart with neither platelet count greater than 60 x 10^9/L. The mean of these 2 platelet counts (mean baseline platelet count) will be used for entry criteria and for assignment to the low or high baseline platelet count cohort. 3. Participants scheduled to undergo a permitted elective procedure who, in the opinion of the investigator, will require a platelet transfusion to address a risk of bleeding associated with the procedure unless there is a clinically significant increase in platelet count from baseline 4. Model For End-stage Liver Disease (MELD) score less than or equal to 24 at Screening 5. If taking inhibitors of P glycoprotein (P-gp), except for verapamil, dose must be stable for 7 days prior to Screening 6. Provide written informed consent 7. Willing and able to comply with all aspects of the protocol

Patient Exclusion Criteria

1. Any history of arterial or venous thrombosis, including partial or complete thrombosis 2. Evidence of thrombosis (partial or complete) in the main portal vein, portal vein branches, or any part of the splenic mesenteric system at Screening 3. Portal vein blood flow velocity rate <10 centimeters/second at Screening 4. Hepatic encephalopathy that cannot be effectively treated 5. Participants with HCC with Barcelona Clinic Liver Cancer (BCLC) staging classification C or D 6. Platelet transfusion or receipt of blood products containing platelets within 7 days of Screening. However packed red blood cells are permitted. 7. Heparin, warfarin, nonsteroidal anti-inflammatory drugs (NSAID), aspirin, verapamil, and antiplatelet therapy with ticlopidine or glycoprotein IIb/IIIa antagonists (eg, tirofiban) within 7 days of Screening 8. Use of erythropoietin stimulating agents within 7 days of Screening 9. Interferon (IFN) use within 14 days of Screening 10. Estrogen-containing hormonal contraceptive or hormone replacement therapy use within 30 days of Screening 11. Active infection requiring systemic antibiotic therapy within 7 days of Screening. However, prophylactic use of antibiotics is permitted. 12. Alcohol abuse, alcohol dependence syndrome, drug abuse, or drug dependence within 6 months of the study start (unless participating in a controlled rehabilitation program) or acute alcoholic hepatitis (chronic alcoholic hepatitis is allowed) within 6 months of the study start 13. Elective procedure performed prior to Visit 4 (Procedure Day) 14. Known to be human immunodeficiency virus positive 15. Any clinically significant acute or active bleeding (eg, gastrointestinal, central nervous system) 16. Known history of any primary hematologic disorder (eg, immune thrombocytopenic purpura, myelodysplastic syndrome) 17. Known medical history of genetic prothrombotic syndromes (eg, Factor V Leiden; prothrombin G20210A; ATIII deficiency, etc.) 18. Participants with a history of significant cardiovascular disease (eg, congestive heart failure New York Heart Association Grade III/IV, arrhythmia known to increase the risk of thromboembolic events [eg, atrial fibrillation], coronary artery stent placement, angioplasty, and coronary artery bypass grafting) 19. Females of childbearing potential who have had unprotected sexual intercourse within 30 days before study entry and who do not agree to use a highly effective method of contraception (eg, total abstinence, an intrauterine device, a double-barrier method [such as condom plus diaphragm with spermicide], a progesterone-only contraceptive implant/injection, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. If currently abstinent, the participant must agree to use a double-barrier method as described above if she becomes sexually active during the study period or for 30 days after study drug discontinuation. All females will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrhea in the appropriate age group and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) at least 1 month before dosing. 20. Females who are lactating or pregnant at Screening or Baseline (as documented by a positive serum beta-human chorionic gonadotropin [B-hCG] test with a minimum sensitivity 25 IU/L or equivalent units of B-hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug. 21. Post liver transplant subjects 22. Any participant who has previously received avatrombopag 23. Hypersensitivity to avatrombopag maleate or any of its excipients 24. Hemoglobin levels ≤ 8.0 or ≥ 18.0 g/dL for men and > 15 for women at Screening, with hematocrit ≥ 54% for men and ≥ 45% for women 25. Current malignancy including solid tumors and hematologic malignancies (except HCC) 26. Any history of concomitant medical condition that, in the opinion of the investigator(s), would compromise the participant's ability to safely complete the study 27. Currently enrolled in another clinical trial with any investigational drug or device within 30 days of Screening

Trial Details

Identifiers

Identifier	Owner
NCT01976104	ClinicalTrials.gov: US National Institutes of Health
E5501G000-311	Eisai
EudraCT2013-000934-36	European Clinical Trials Database
JapicCTI142746	Japan Pharmaceutical Information Center - Clinical Trials Information
14-000830	Mayo Clinic
IRB14-000830	Mayo Clinic
P309-2011	Paediatric Investigation Plan EMA Decision number
17160	United Kingdom Clinical Research Network
HEPA3323	-

Organisations

Sponsors Dova Pharmaceuticals; Eisai Inc
Affiliations Dova Pharmaceuticals; Eisai Inc

Trial Dates

Initiation Dates
Planned : 01 Nov 2013

Actual : 01 Nov 2013
Primary Completion Dates
Planned : 01 Dec 2016

Actual : 30 Jan 2017
End Dates
Planned : 01 Dec 2016

Actual : 21 Feb 2017

Other Details

Design double-blind; multicentre; parallel; prospective; randomised
Phase of Trial Phase III
Location Argentina; Australia; Belgium; Brazil; Canada; China; Czech Republic; France; Germany; Israel; Italy; Japan; Mexico; Romania; Russia; Spain; USA
Focus Registrational; Therapeutic Use

Interventions

Drugs	Route	Formulation
AvatrombopagPrimary Drug	Oral	Tablet

Placebo

Group B: lower baseline platelet count, Group D: higher baseline platelet count

Avatrombopag (lower baseline platelet count)

Group A
Avatrombopag (Dosage: 60 mg/day; Formulation: tablet; Frequency: od d1-5; Company: Eisai Inc)

Avatrombopag (higher baseline platelet count)

Group C
Avatrombopag (Dosage: 40 mg/day; Formulation: tablet; Frequency: od d1-5; Company: Eisai Inc)

Results

Therapeutic efficacy

The phase III, ADAPT-2 trial met its primary and secondary efficacy endpoints with high statistical significance. In patients with low baseline platelet count (<40 x 10⁹/L), 69% of avatrombopag patients did not need platelet transfusion or bleeding rescue, compared with 35% on placebo (p<0.0006). Patients with high baseline platelet count (40 to <50 x 10⁹/L) had significantly less need for platelet transfusion or bleeding rescue (89% vs 33%). Avatrombopag was superior to placebo for both secondary endpoints, increasing mean platelet counts on procedure day to 85 x 10⁹/L. The trial enrolled 231 patients with thrombocytopenia associated with chronic liver disease undergoing an elective procedure^[3].

Adverse events

Phase III: Updated safety results from phase III study for avatrombopag in patients with idiopathic-thrombocytopenic-purpura showed treatment-emergent adverse events (TEAEs) were reported in 85.4% and 76.9% subjects treated with avatrombopag and placebo, respectively; exposure adjusted incidence of TEAEs was similar between two groups; no treatment-related SAEs were reported. In the whole study, the exposure-adjusted incidence of TEAEs in the avatrombopag group was consistent with that of the core treatment phase; 98.6% and 19.4% of subjects treated with avatrombopag reported TEAEs and SAEs, respectively. Earlier,in the phase III, ADAPT-1 and 2 trials, the most common treatment-emergent adverse events (TEAE) were pyrexia, abdominal pain, nausea, fatigue, oedema peripheral and headache, which were similar for placebo and avatrombopag arms in both studies. Most adverse events were mild to moderate in severity. Portal vein thromboses was reported in patients with chronic liver disease and in patients receiving TPO receptor agonists. One treatment-emergent event of portal vein thrombosis was reported in the both studies in an avatrombopag-treated patient (n = 1/430). The thrombotic TEAE occurred with 40mg avatrombopag in cohort 2 in ADAPT2^[4]^[3].

Publications

Dova Pharmaceuticals. Dova Pharmaceuticals Announces New Drug Application Submission to FDA for Avatrombopag, a Second Generation Thrombopoietin Receptor Agonist. Media-Rel 2017;.
Media Release
Terrault N, Bibbiani F, Chen Y-C, Izumi N, Kayali Z, Lazcano Soto JR, et al. Superiority of Avatrombopag (AVA) to Placebo (PBO) for the Treatment of Chronic Liver Disease (CLD)-Associated Thrombocytopenia (TCP) in Patients Undergoing Scheduled Proce-dures: Results of 2 Randomized, PBO-Con-trolled Phase 3 Studies. AASLD-2017 2017; abstr. 217.
Available from: URL: http://onlinelibrary.wiley.com/doi/10.1002/hep.29500/epdf
Qamar A, aggarwal k, Vredenburg M, Tian W, Allen LF. Splenomegaly status does not impact the efficacy of avatrombopag in increasing platelet counts and reducing platelet transfusions or rescue procedures for bleeding in chronic liver disease patients with thrombocytopenia. ILC-2019 2019; abstr. SAT-135.
Available from: URL: https://ilc-congress.eu/
Saab S, Alkhouri N, Allen LF, Aggarwal K, Vredenburg M, Tian W. Efficacy of Avatrombopag Compared with Placebo Across Various Mean Baseline Platelet Count Subgroups- Pooled Data from 2 Phase 3 Studies. DDW-2018 2018; abstr. Tu1553.
Available from: URL: https://ep70.eventpilot.us/web/page.php?nav=false&page=IntHtml&project=DDW18&id=2912817&plannersession=true
Sammy S, Alkhouri N, Allen LF, Aggarwal K, Vredenburg M, Tian W, et al. Efficacy of avatrombopag compared with placebo across various mean baseline platelet count subgroups- pooled data from 2 Phase 3 studies. ILC-2018 2018; abstr. SAT-318.
Available from: URL: http://ilc-congress.eu/
Terrault N, Chen YC, Izumi N, Kayali Z, Mitrut P, Tak WY, et al. Avatrombopag Before Procedures Reduces Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia. Gastroenterology 2018;.
PubMed | CrossRef Fulltext
Reau NS, Sammy S, Allen LF, Aggarwal K, Vredenburg M, Kim WR. Avatrombopag decreases need for platelet transfusion in patients chronic liver disease and thrombocytopenia undergoing medical procedures with low to high associated bleeding risks. ILC-2018 2018; abstr. SAT-317.
Available from: URL: http://ilc-congress.eu/
Saab S, Vredenburg M, Wheeler N, Chi A, Peyton AL. Decreased use of Rescue Therapy for Emergent Bleeds Following a Procedure and Fewer Procedure-Related Bleeds Overall with Avatrombopag Treatment in Chronic Liver Disease. AASLD-2020 2020; abstr. 1876.
Available from: URL: https://aasld.confex.com/aasld/2020/meetingapp.cgiPaper/21942
Alkhouri N, aggarwal k, Vredenburg M, Tian W, Allen LF. Hepatocellular carcinoma does not impact the efficacy of avatrombopag in increasing platelet counts and reducing platelet transfusions or rescue procedures for bleeding in chronic liver disease patients with thrombocytopenia. ILC-2019 2019; abstr. SAT-136.
Available from: URL: https://ilc-congress.eu/
Nomoto M, Ferry J, Hussein Z. Population Pharmacokinetic/Pharmacodynamic Analyses of Avatrombopag in Patients With Chronic Liver Disease and Optimal Dose Adjustment Guide With Concomitantly Administered CYP3A and CYP2C9 Inhibitors. J-Clin-Pharmacol 2018;.
PubMed | CrossRef Fulltext
Saab S, Allen LF, Aggarwal K, Vredenburg M, Terrault N. Consistent Efficacy of Avatrombopag Compared to Placebo in Patients with Thrombocytopenia and Chronic Liver Disease Undergoing Procedures Across Various Liver Disease Severities and Etiologies. DDW-2018 2018; abstr. Tu1548.
Available from: URL: https://ep70.eventpilot.us/web/page.php?nav=false&page=IntHtml&project=DDW18&id=2913002&plannersession=true
Sammy S, Allen LF, Aggarwal K, Vredenburg M, Terrault N. Consistent efficacy of avatrombopag compared to placebo in patients with thrombocytopenia and chronic liver disease undergoing procedures across various disease severities and etiologies. ILC-2018 2018; abstr. SAT-319.
Available from: URL: http://ilc-congress.eu/
Dova Pharmaceuticals. Dova Pharmaceuticals Announces U.S. FDA Approval of DOPTELET(R)(avatrombopag). Media-Rel 2018;.
Media Release
Frelinger III AL, Koganov ES, Forde EE, Carmichael SL, Michelson AD. Avatrombopag, a Novel Thrombopoietin Receptor Agonist, Increases Platelet Counts without Increasing Platelet Activation in Patients with Thrombocytopenia Due to Chronic Liver Disease. ASH-Hem-2017 2017; abstr. 290.
Available from: URL: https://ash.confex.com/ash/2017/webprogram/Paper104502.html
Poordad F, Vredenburg M, Allen LF, Aggarwal K, Alkhouri N. Superiority of Avatrombopag to Placebo in Increasing Platelet Counts and Reducing Platelet Transfusions in Patients with Chronic Liver Disease-Associated Thrombocytopenia Undergoing Scheduled Procedures- Pooled Analysis of 2 Randomized Phase 3 Studies. DDW-2018 2018; abstr. Su1468.
Available from: URL: https://ep70.eventpilot.us/web/page.php?nav=false&page=IntHtml&project=DDW18&id=2912956&plannersession=true
Michelson AD, Smolensky Koganov E, Forde EE, Carmichael SL, Frelinger AL 3rd. Avatrombopag Increases Platelet Count but Not Platelet Activation in Patients with Thrombocytopenia due to Liver Disease. J-Thromb-Haemost 2018;.
PubMed | CrossRef Fulltext
Caldwell S, Alkhouri N, Allen LF, Aggarwal K, Vredenburg M, Tian W, et al. Characterization of Baseline Thrombopoietin Levels in Patients With Chronic Liver Disease: Results From 2 Pooled Clinical Studies in Patients With Thrombocytopenia and Liver Disease. ACG-2018 2018; abstr. P0606.
Available from: URL: https://www.eventscribe.com/2018/ACG/ajaxcalls/PosterInfo.asp?efp=RFNSWFFHSFY2NDI0&PosterID=163067&rnd=0.7672061
Poordad F, Allen LF, Aggarwal K, Vredenburg M, Alkhouri N. Superiority of Avatrombopag to Placebo in I Reducing Platelet Transfusions in Patients with Thrombocytopenia and Chronic Liver Disease Undergoing Scheduled Procedures- Pooled Analysis of 2 Studies. EHA-2018 2018; abstr. PS1401.
Available from: URL: https://learningcenter.ehaweb.org/eha/2018/stockholm/215691/kavita.aggarwal.superiority.of.avatrombopag.to.placebo.in.i.reducing.platelet.html?f=menu=6*ce_id=1346*ot_id=19068*media=3*marker=167
Terrault N, Kuter DJ, Izumi N, Kayali Z, Mitrut P, Tak WY, et al. Superiority of Avatrombopag to Placebo in Increasing Platelet Counts in Patients with Chronic Liver Disease-Associated Thrombocytopenia Undergoing Scheduled Procedures: Results from 2, Phase 3 Randomized Studies. ASH-Hem-2017 2017; abstr. 18.
Available from: URL: https://ash.confex.com/ash/2017/webprogram/Paper105516.html
Vredenburg M, Reau N, Allen LF, Aggarwal K, Poordad F. Consistent Efficacy of Avatrombopag over Placebo in the Treatment of Thrombocytopenia in Patients with Chronic Liver Disease Undergoing Invasive Procedures Across Demographic Subgroups - Pooled Results of Two Phase 3 Studies. DDW-2018 2018; abstr. Su1475.
Available from: URL: https://ep70.eventpilot.us/web/page.php?nav=false&page=IntHtml&project=DDW18&id=2913068&plannersession=true

Authors

Author	Total Publications	First Author	Last Author
Aggarwal K	11	-	-
Alkhouri N	6	1	2
Allen LF	12	-	2
Bibbiani F	2	-	1
Caldwell S	1	1	-
Carmichael SL	2	-	-
Chen Y-C	1	-	-
Chen YC	1	-	-
Chi A	1	-	-
Dova Pharmaceuticals	2	2	2
Ferry J	1	-	-
Forde EE	2	-	-
Frelinger AL 3rd	1	-	1
Frelinger III AL	1	1	-
Hassanein T	1	-	1
Hassanein TI	1	-	1
Hussein Z	1	-	1
Izumi N	3	-	-
Kayali Z	3	-	-
Kim WR	1	-	1
Koganov ES	1	-	-
Kuter DJ	1	-	-
Lazcano Soto JR	1	-	-
Michelson AD	2	1	1
Mitrut P	3	-	-
Nomoto M	1	1	-
Peyton AL	1	-	1
Poordad F	3	2	1
Qamar A	1	1	-
Reau N	1	-	-
Reau NS	1	1	-
Saab S	3	3	-
Sammy S	3	2	-
Shah N	1	-	1
Smolensky Koganov E	1	-	-
Tak WY	3	-	-
Terrault N	6	3	3
Tian W	5	-	1
Vredenburg M	12	1	-
Wheeler N	1	-	-

Trial Centres

Centres

Download Data (CSV)

Centre Name	Location	Trial Centre Country
-	Aracaju	Brazil
-	Arad	Romania
-	Baggiovara, Modena	Italy
-	Baltimore, Maryland	USA
-	Barcelona	Spain
-	Beijing, Beijing	China
-	Birmingham, Alabama	USA
-	Bonn, Nordrhein Westfalen	Germany
-	Boston, Massachusetts	USA
-	Botucatu	Brazil
-	Brno	Czech-Republic
-	Bucharest	Romania
-	Bucuresti	Romania
-	Bunkyo-ku, Tokyo	Japan
-	Caceres, Cáceres	Spain
-	Calgary	Canada
-	Charleston, South Carolina	USA
-	Charlottesville, Virginia	USA
-	Chengdu, Sichuan	China
-	Chiba	Japan
-	Chiyoda, Tokyo	Japan
-	Ciudad Autonoma Buenos Aires	Argentina
-	Clayton, Victoria	Australia
-	Clichy cedex, Hauts De Seine	France
-	Cordoba	Argentina
-	Coronado, California	USA
-	Craiova	Romania
-	Denver, Colorado	USA
-	Detroit, Michigan	USA
-	Durango	Mexico
-	Edegem	Belgium
-	Edmonton	Canada
-	Firenze	Italy
-	Footscray, Victoria	Australia
-	Frankfurt, Hessen	Germany
-	Gent	Belgium
-	Girona	Spain
-	Haifa	Israel
-	Hamburg	Germany
-	Hangzhou, Zheijiang	China
-	Hannover, Niedersachsen	Germany
-	Havirov	Czech-Republic
-	Hefei, Anhui	China
-	Holon	Israel
-	Hospitalet de Llobregat, Barcelona	Spain
-	Houston, Texas	USA
-	Iasi	Romania
-	Indianapolis, Indiana	USA
-	Iruma, Saitama	Japan
-	Jerusalem	Israel
-	Kansas City, Kansas	USA
-	Kansas City, Missouri	USA
-	Kemerovo	Russia
-	Kiel, Schleswig Holstein	Germany
-	Leipzig, Sachsen	Germany
-	Liege	Belgium
-	Little Rock, Arkansas	USA
-	Loma Linda, California	USA
-	Lyon Cedex 04, Rhone	France
-	Madrid	Spain
-	Mannheim, Baden Wuerttemberg	Germany
-	Maywood, Illinois	USA
-	Melbourne, Victoria	Australia
-	Merida, Yucatán	Mexico
-	Miami, Florida	USA
-	Milano	Italy
-	Monterrey, Nuevo León	Mexico
-	Morioka, Iwate	Japan
-	Moscow	Russia
-	Musashino, Tokyo	Japan
-	Nahariya	Israel
-	Nanjing, Jiangsu	China
-	New Orleans, Louisiana	USA
-	New York, New York	USA
-	Nice Cedex 3, Alpes Maritimes	France
-	Niigata	Japan
-	Nishinomiya, Hyogo	Japan
-	Okayama	Japan
-	Okayama-shi, Okayama	Japan
-	Orizaba, Veracruz	Mexico
-	Osaka-Sayama-shi, Osaka	Japan
-	Osaka-shi, Osaka	Japan
-	Ostrava	Czech-Republic
-	Parkville, Victoria	Australia
-	Petach Tikva	Israel
-	Phoenix, Arizona	USA
-	Pisa	Italy
-	Porto Alegre	Brazil
-	Praha 2	Czech-Republic
-	Praha 4	Czech-Republic
-	Ramat-Gan	Israel
-	Rechovot	Israel
-	Rennes cedex 09, Ille Et Vilaine	France
-	Richmond, Virginia	USA
-	Roma	Italy
-	Rosario	Argentina
-	Saint Petersburg	Russia
-	Salvador	Brazil
-	Samara	Russia
-	San Antonio, Texas	USA
-	Sapporo-shi, Hokkaido	Japan
-	Seattle, Washington	USA
-	Setagaya-ku, Tokyo	Japan
-	Shijiazhuang, Hebei	China
-	Shinagawa-ku, Tokyo	Japan
-	Sibiu	Romania
-	Statesville, North Carolina	USA
-	Takamatsu, Kagawa	Japan
-	Tel Aviv	Israel
-	Timisoara	Romania
-	Tokushima	Japan
-	Trento	Italy
-	Tuebingen, Baden Wuerttemberg	Germany
-	Usti nad Labem	Czech-Republic
-	Valencia	Spain
-	Villejuif, Val De Marne	France
-	Wakayama	Japan
-	Xi'an, Shaanxi	China
-	Xi'an, Shanxi	China
-	Yufu, Oita	Japan
-	Zapopan, Jalisco	Mexico
-	Zaragoza	Spain
Eisai Inc. Phone: 1-888-422-4743 Division: Inquiry service https://inquiry.eisai.co.jp/webapp/form/17672_sdab_2/index.do show details	-	-

Trial History

Event Date	Event Type	Comment
06 Nov 2023	Other trial event	According to a Sobi North America media release, based on data from ADAPT 1 and ADAPT 2 and other phase 2 and phase 3 studies for chronic ITP, Health Canada has approved avatrombopag, an oral thrombopoietin receptor agonist , for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP). Updated 15 Apr 2024
17 Nov 2020	Results	Results of a post hoc analysis of data pooled from ADAPT-1 and 2 studies assessing the procedure-related bleeding and the need for rescue therapy for bleeding events with AVA presented at The Liver Meeting 2020 70th Annual Meeting of the American Association for the Study of Liver Diseases Updated 27 Jan 2021
30 Apr 2020	Other trial event	According to a Dova Pharmaceuticals media release, DOPTELET (avatrombopag) has been granted approval from the China National Medical Products Administration (NMPA) for the treatment of thrombocytopenia in adult patients with chronic liver disease (CLD) who are scheduled to undergo a procedure (i.e., the CLD indication).The approval was based on safety and efficacy data from two global Phase 3, double-blind, placebo-controlled trials (NCT01972529 and NCT01976104). Updated 05 May 2020
27 Jun 2019	Other trial event	According to an Dova Pharmaceuticals media release, the company will host a conference call to discuss the approval by FDA. Updated 02 Jul 2019
27 Jun 2019	Other trial event	According to an Dova Pharmaceuticals media release, the U.S. Food and Drug Administration(FDA) has approved a supplemental New Drug Application(sNDA) that expands the use of DOPTELET(avatrombopag) to include the treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. Updated 02 Jul 2019
25 Jun 2019	Other trial event	According to a Dova Pharmaceuticals media release, based on the results of ADAPT-1 and ADAPT-2 trials the European Commission (EC) has granted marketing authorization for DOPTELET (avatrombopag) for the treatment of severe thrombocytopenia in adult patients with chronic liver disease (CLD) who are scheduled to undergo an invasive procedure. Updated 27 Jun 2019
14 Apr 2019	Results	Results assessing the impact of Hepatocellular carcinoma on the efficacy of avatrombopag in ADAPT-1 and ADAPT-2 trials, presented at The International Liver Congress 2019 Updated 12 Sep 2019
14 Apr 2019	Results	Results assessing the impact of Splenomegaly on the efficacy of avatrombopag in ADAPT-1 and ADAPT-2 trials, resented at The International Liver Congress 2019 Updated 12 Sep 2019
05 Nov 2018	Other trial event	According to a Dova Pharmaceuticals media release, the U.S. Food and Drug Administration (FDA) has accepted for review the supplemental New Drug Application (sNDA) for DOPTELET (avatrombopag) for a new indication, the treatment of chronic immune thrombocytopenia (ITP) in patients who have had an insufficient response to a previous treatment. The Prescription Drug User Fee Act (PDUFA) goal date for an FDA decision on the sNDA is June 30, 2019. Updated 11 Mar 2019
10 Oct 2018	Results	Results presented at the American College of Gastroenterology Annual Scientific Meeting and Postgraduate Course 2018 Updated 05 Nov 2018
28 Sep 2018	Results	Results from ADAPT 1 and ADAPT 2 studies published in the Journal of Thrombosis and Haemostasis Updated 21 Nov 2018
04 Sep 2018	Other trial event	According to a Dova Pharmaceuticals media release, the company has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for DOPTELET (avatrombopag), seeking approval for the treatment of adult patients with immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. Data from the study supported the application. Updated 11 Mar 2019
09 Aug 2018	Other trial event	England, European Union, Taiwan, Thailand, United Kingdom were the planned locations for this study. European Clinical Trials Database Updated 21 Aug 2018
17 Jun 2018	Results	Results of a pooled analysis from ADAPT-1 and ADAPT-2 trials (n=435) presented at the 23rd Congress of the European Haematology Association Updated 20 Jul 2018
15 Jun 2018	Results	Results of pooled data from 14 trials, were published in the Journal of Clinical Pharmacology. Updated 11 Jul 2018
05 Jun 2018	Results	Results evaluating the efficacy of Avatrombopag compared to placebo (PBO) in increasing platelet counts (PC) and reducing the need for platelet transfusion from two randomized trials (ADAPT-1 and ADAPT-2) presented at the Digestive Disease Week 2018 Updated 19 Jul 2018
05 Jun 2018	Results	Results of pooled analysis of 2 randomized phase 3 studies (ADAPT-1 and ADAPT-2) presented at the Digestive Disease Week 2018 Updated 17 Jul 2018
05 Jun 2018	Results	Pooled subgroup analysis results of ADAPT-1 and ADAPT-2 trials evaluating the efficacy of AVA in increasing platelet count (PC) in various subgroups based on their pre-treatment PC at baseline presented at the Digestive Disease Week 2018 Updated 16 Jul 2018
05 Jun 2018	Results	Pooled subgroup analysis results of ADAPT-1 and ADAPT-2 evaluating the efficacy of AVA compared to placebo in various patient subgroups presented at the Digestive Disease Week 2018 Updated 16 Jul 2018
04 Jun 2018	Other trial event	Data from ADAPT-1 and ADAPT-2 trials will be presented at 64th International Society on Thrombosis and Haemostasis (ISTH) Annual Scientific and Standardization Committee (SSC) Meeting 2018, according to a Dova Pharmaceuticals media release. Updated 08 Jun 2018
04 Jun 2018	Other trial event	Data from ADAPT-1 and ADAPT-2 trials will be presented at the 23rd Congress of the European Hematology Association (EHA) 2018 meeting, according to a Dova Pharmaceuticals media release. Updated 08 Jun 2018
04 Jun 2018	Other trial event	Pooled data from ADAPT-1 and ADAPT-2 trials will be presented at the Digestive Disease Week (DDW) 2018 meeting, according to a Dova Pharmaceuticals media release. Updated 08 Jun 2018
21 May 2018	Results	Results presented in the Dova Pharmaceuticals media release. Updated 28 May 2018
21 May 2018	Other trial event	According to a Food and Drug Administration media release, based on the data from ADAPT-1 and ADAPT-2 trials, the U.S. Food and Drug Administration has approved Doptelet (avatrombopag) tablets to treat low blood platelet count (thrombocytopenia) in adults with chronic liver disease who are scheduled to undergo a medical or dental procedure. Updated 28 May 2018
17 May 2018	Results	Results of ADAPT-1 and ADAPT-2 studies, published in the Gastroenterology Updated 24 May 2018
14 Apr 2018	Results	Results of a pooled analysis from ADAPT-1 and ADAPT-2 studies, presented at The International Liver Congress 2018 Updated 08 Jun 2018
14 Apr 2018	Results	Results of a pooled analysis from ADAPT-1 and ADAPT-2 studies, presented at The International Liver Congress 2018 Updated 08 Jun 2018
14 Apr 2018	Results	Results of a pooled analysis from ADAPT-1 and ADAPT-2 studies, presented at The International Liver Congress 2018 Updated 08 Jun 2018
12 Apr 2018	Other trial event	Last checked against the Japan Pharmaceutical Information Center - Clinical Trials Information record. Japan Pharmaceutical Information Center - Clinical Trials Information Updated 12 Apr 2018
28 Feb 2018	Other trial event	Last checked against the ClinicalTrials.gov record. ClinicalTrials.gov: US National Institutes of Health Updated 28 Feb 2018
27 Feb 2018	Biomarker Update	Biomarkers information updated Updated 07 Nov 2021
16 Feb 2018	Other trial event	Last checked against European Clinical Trials Database record. European Clinical Trials Database Updated 16 Feb 2018
12 Dec 2017	Results	Results of association of increase of platelet counts without increasing platelet activation by using data from two studies including this study presented at the 59th Annual Meeting and Exposition of the American Society of Hematology. Updated 28 Dec 2017
12 Dec 2017	Results	Results of ADAPT 1 and ADAPT 2 studies assessing superiority of Avatrombopag to placebo, presented at the 59th Annual Meeting and Exposition of the American Society of Hematology. Updated 22 Dec 2017
04 Dec 2017	Other trial event	According to a Dova Pharmaceuticals media release, data from the study will be presented at the 59th American Society of Hematology (ASH) Annual Meeting and Exposition. Updated 06 Dec 2017
27 Nov 2017	Other trial event	According to a Dova Pharmaceuticals media release, the NDA for avatrombopag has been accepted for filing and has been granted Priority Review by the United States Food and Drug Administration (FDA). The submission is based on ADAPT 1 and ADAPT 2 trials. The Prescription Drug User Fee Act (PDUFA) goal date for an FDA decision is May 21, 2018. Updated 29 Nov 2017
24 Oct 2017	Results	Results from ADAPT 1 and ADAPT 2 studies, presented at The Liver Meeting 2017: 68th Annual Meeting of the American Association for the Study of Liver Diseases Updated 17 Nov 2017
22 Sep 2017	Other trial event	According to a Dova Pharmaceuticals media release, based on the data from ADAPT-1 and ADAPT-2 trials the company has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for avatrombopag, for the treatment of thrombocytopenia in patients with chronic liver disease (CLD) who are scheduled to undergo a procedure. Updated 26 Sep 2017
22 Sep 2017	Results	Results published in a Dova Pharmaceuticals media release. Updated 26 Sep 2017
22 Sep 2017	Endpoint met	Primary endpoint has been met. (Proportion of participants who do not require a platelet transfusion or any rescue procedure for bleeding after randomization and up to 7 days following an elective procedure), according to a Dova Pharmaceuticals media release. Updated 26 Sep 2017
10 Aug 2017	Other trial event	According to a Dova Pharmaceuticals media release, data from ADAPT-1 and ADAPT-2 trials has been accepted for presentation at the American Association for the Study of Liver Disease Annual Meeting Updated 16 Aug 2017
09 Jun 2017	Status change - completed	Status changed from active, no longer recruiting to completed. ClinicalTrials.gov: US National Institutes of Health Updated 14 Jun 2017
06 Jan 2017	Status change - active, no longer recruiting	Status changed from recruiting to active,no longer recruiting, as reported in a Dova Pharmaceuticals media release. Updated 08 May 2017
24 May 2016	Other trial event	New source identified and integrated (Japan Pharmaceutical Information Center - Clinical Trials Information; JapicCTI142746) Japan Pharmaceutical Information Center - Clinical Trials Information Updated 24 May 2016
19 May 2016	Other trial event	According to a PBM media release, this phase III study is conducted under a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration as a potential treatment for thrombocytopenia in patients with chronic liver disease undergoing an elective procedure. Updated 25 May 2016
15 Feb 2016	Other trial event	New source identified and integrated: United Kingdom Clinical Research Network (17160). United Kingdom Clinical Research Network Updated 15 Feb 2016
20 Mar 2015	Completion date	According to the ClinicalTrials.gov record, planned end date changed from 1 Aug 2015 to 1 Dec 2016. ClinicalTrials.gov: US National Institutes of Health Updated 02 Apr 2015
20 Mar 2015	Other trial event	According to the ClinicalTrials.gov record, planned primary completion date changed from 1 Jul 2015 to 1 Dec 2016. ClinicalTrials.gov: US National Institutes of Health Updated 02 Apr 2015
20 Dec 2014	Other trial event	Planned primary completion date changed from 1 May 2015 to 1 Jul 2015 according to ClinicalTrial.gov record. ClinicalTrials.gov: US National Institutes of Health Updated 31 Dec 2014
25 Jun 2014	Other trial event	New source identified and integrated (European Clinical Trials Database; EudraCT2013-000934-36). European Clinical Trials Database Updated 25 Jun 2014
15 Apr 2014	Other trial event	New source identified and integrated (Mayo Clinic: 14-000830). Updated 15 Apr 2014
17 Jan 2014	Status change - recruiting	Status changed from not yet recruiting to recruiting according to ClinicalTrial.gov record. ClinicalTrials.gov: US National Institutes of Health Updated 27 Feb 2014
13 Nov 2013	New trial record	New trial record ClinicalTrials.gov: US National Institutes of Health Updated 13 Nov 2013

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