A Phase III Randomized Placebo-Controlled Study to Examine the Efficacy and Safety of DAS181 for the Treatment of Lower Respiratory Tract Parainfluenza Infection in Immunocompromised Subjects

At a glance

Drugs Oplunofusp (Primary)
Indications COVID 2019 infections; Parainfluenza virus infections
Focus Registrational; Therapeutic Use
Acronyms RCT; STOP PIV
Sponsors Ansun Biopharma

Most Recent Events

23 Mar 2021 Planned End Date changed from 28 Dec 2021 to 31 Dec 2023.
17 Feb 2021 Planned number of patients changed from 250 to 274.
21 Jan 2021 This trial is Discontinued in Denmark, according to European Clinical Trials Database record.

Trial Overview

Purpose

This phase III study is designed to examine the efficacy and safety of DAS181 for the treatment of lower respiratory tract parainfluenza infection in immunocompromised subjects. Patients will receive the treatment twice a day from between 10 to 14 days, depending on their response.

Primary Endpoints

Percent of subjects who Return to Room Air (RTRA) (main study)

description: Removal of all oxygen support (with stable SpO2)
time_frame: by Day 28

Percent of subjects with improved COVID-19 Clinical Status Scale (sub-study)

time_frame: Day 14

Other Endpoints

All-cause mortality rate (main study)

time_frame: at Day 28
time_frame: at Day 35

Percent of subjects who Return to Room Air (RTRA) (main study)

time_frame: by Day 21

Time (in days) to RTRA (main study)

time_frame: Days 10, 14, 21, 28

Percent of subjects who achieve clinical stability (main study)

time_frame: by Day 28

Percent of subjects discharged (without mortality and hospice) (main study)

time_frame: by Days 14, 21, 28 and 35

Time (in days) to first hospital discharge (without hospice) (main study)

time_frame: through Day 35

Total number of inpatient days (main study)

time_frame: up to Day 35

Baseline SAD-RV infection-related mortality rate (main study)

time_frame: at Day 28
time_frame: at Day 35

Change in pulmonary function (FEV1% predicted) (main study)

time_frame: Day 1, Day 7, Day 14, Day 28

Time to improved COVID19 clinical status (Sub-study)

time_frame: Day 5, Day 10, Day 21, Day 28

Time to RTRA

time_frame: Day 10, Day 14, Day 21, Day 28

Time to Clinical stability

time_frame: Day 14, Day 21, Day 28

Time to SARS-CoV-2 RNA in the respiratory specimens being undetectable

time_frame: Day 5, Day 10, Day 14, Day 21, Day 28

Time to Clinical deterioration

time_frame: Day 5, Day 10, Day 14, Day 21, Day 28

Time to Discharge from hospital (without readmission before Day 28).

time_frame: Day 14, Day 21, Day 28

Time to Death (all causes)

time_frame: Day 14, Day 21, Day 28^[1]

Diseases Treated

Indication	Qualifiers	Patient Segments
COVID 2019 infections	treatment	-
Parainfluenza virus infections	treatment	-

Subjects

Subject Type patients
Number
Planned: 274
Sex male & female
Age Group ≥ 12 years; adolescent; adult; child; elderly

Patient Inclusion Criteria

1. At the time of randomization, requires supplemental oxygen ≥2 LPM due to hypoxemia. 2. Immunocompromised, as defined by one or more of the following: - Received an autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at any time in the past - Received a solid organ transplant at any time in the past - Has been or is currently being treated with chemotherapy for hematologic malignancies (e.g., leukemia, myeloma, lymphoma) and/or solid tumor malignancies (e.g., lung, breast, brain cancer) at any time in the past - Has an immunodeficiency due to congenital abnormality (only applicable to subjects age < 18 years old) or pre-term birth (only applicable to subjects age ≤ 2 years old) 3. Has, within 3 days prior to randomization, a confirmed LRTI with a sialic acid dependent respiratory virus 4. If female, subject must meet one of the following conditions: - Not be of childbearing potential or - Be of childbearing potential and have a negative urine/serum pregnancy test and agrees to practice an acceptable method of contraception 5. Non-vasectomized males are required to practice effective birth control methods 6. Capable of understanding and complying with procedures as outlined in the protocol 7. Provides signed informed consent prior to the initiation of any screening or study-specific procedures For COVID-19 sub study: 1. Be ≥18 years of age 2. Provide adequate medical history to permit accurate stratification (but health status may be healthy, high-risk conditions, or immunocompromised). 3. Prior to SARS CoV 2 infection, has the ability to carry out self-care activities of daily living (basic ADL) 4. Have lower respiratory tract infection (LRTI) confirmed by CT imaging, with or without contrast, to involve at least 2 lobes of the lung. 5. Has laboratory-confirmation of the presence of SARS CoV 2 in the respiratory tract by at least one of the following samples 6. Satisfy inclusion criteria #1, 4, 5, 6, 7 of the main study

Patient Exclusion Criteria

1. Subjects may not be on hospice care or, in the opinion of the investigator, have a low chance of survival during the first 10 days of treatment 2. Subjects with Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), or Alkaline Phosphatase (ALP) ≥3x ULN and Total Bilirubin (TBILI) ≥2x ULN Note: Subjects with ALT/AST/ALP ≥ 3x ULN AND TB ≥2x ULN that have been chronically stable (for >1 year on more than one assessments) due to known liver pathology including malignancy (primary or metastasis), chronic medications, transplantation, or chronic infection will not be excluded 3. Female subjects breastfeeding or planning to breastfeed at any time through 30 days after the last dose of study drug 4. Subjects taking any other investigational drug used to treat pulmonary infection. 5. Psychiatric or cognitive illness or recreational drug/alcohol use that, in the opinion of the principal investigator, would affect subject safety and/or compliance 6. Subjects with known hypersensitivity to DAS181 and/or any of its components 7. Subjects with severe sepsis due to either their baseline SAD-RV infection or a concurrent viral, bacterial, or fungal infection and meet at least one of the following criteria: - Has evidence of vital organ failure outside of the lung (e.g., liver, kidney) - Requires vasopressors to maintain blood pressure For COVID-19 sub study: 1. Subjects requiring invasive mechanical, Bi-PAP or CPAP ventilation at randomization. 2. Subjects receiving any other investigational or empiric treatment for SARS-2-CoV (either as part of a clinical trial or under emergency approval (approved agents for the management of symptoms, e.g., fever, are permitted). 3. Subjects who are known HIV-positive (and not undetectable at most recent HIV RNA assessment) 4. Subjects who are currently taking immunomodulating biologics (e.g, interferons, interleukin) 5. Subjects with severe sepsis due to either their SARS-CoV-2 infection or a concurrent viral, bacterial, or fungal infection and meeting at least one of the following criteria: - Have evidence of vital organ failure outside of the lung (e.g., liver, kidney) - Require vasopressors to maintain blood pressure 6. Subjects meeting exclusion criteria #2, 3, 5 and 6 of the main study

Trial Details

Identifiers

Identifier	Owner
NCT03808922	ClinicalTrials.gov: US National Institutes of Health
EudraCT2018-004318-16	European Clinical Trials Database
DAS181-3-01	-

Organisations

Sponsors Ansun Biopharma
Affiliations Ansun Biopharma

Trial Dates

Initiation Dates
Planned : 28 Mar 2019

Actual : 23 May 2019
Primary Completion Dates
Planned : 30 Apr 2021
End Dates
Planned : 31 Dec 2023

Substudies/Extensions

1. Main/Parent Optional Pharmacokinetics Sub-Study Information Sheet and Consent Form, version 2.0 dated 21Feb2019. 2. Pediatric Pharmacokinetic Sub-Study Assent Form (12&NDASH;17 Years Old) Assent of a Minor to Be in an Investigational Study, version 2.0 dated 21Feb2019. Objective is to investigate how the study drug is processed by the body by checking how much of the study drug is in the bloodstream at a particular point in time.

This study contains a sub-study to enroll patients with severe COVID-19.

Other Details

Design double-blind; multicentre; parallel; prospective; randomised
Phase of Trial Phase III
Location Asia; Australia; Belgium; China; Denmark; Europe; France; Germany; Hong Kong; Italy; South Korea; Spain; Taiwan; USA
Focus Registrational; Therapeutic Use

Related Trials

Trial Title	Status	Relationship
DAS181 for Severe COVID-19: Compassionate Use	Completed	Child

Related Drugs

Drug Name	Highest Phase	Originator
Oplunofusp - Ansun Biopharma	Phase III	NexBio

Interventions

Drugs	Route	Formulation
OplunofuspPrimary Drug	Inhalation	Solution

Cohort 1 and Cohort 2 Treatment

DAS181 4.5mg qd x 7 OR 10 days Drug: DAS181 (DAS181 4.5mg nebulized qd x 7 OR 10 days)

Cohort 1 and Cohort 2 Placebo

Placebo qd x 7 OR 10 days Drug: Placebo (Placebo nebulized qd x 7 OR 10 days)

DAS181 COVID-19 Placebo

Placebo q12h x 7 OR 10 days Drug: Placebo (Placebo nebulized qd x 7 OR 10 days)

DAS181 COVID-19 Treatment

DAS181 4.5mg q12h x 7 OR 10 days Drug: DAS181 COVID-19 (DAS181 4.5mg nebulized q12h/day x 7 OR 10 days)

Cohort 3

DAS181 4.5mg qd x 7 OR 10 days (≥ 40 kg) DAS181 2.5mg qd x 7 OR 10 days (< 40kg) Drug: DAS181 OL (DAS181 4.5mg nebulized qd x 7 OR 10 days ≥ 40kg DAS181 2.5mg nebulized qd x 7 OR 10 days < 40kg)

Cohort 4

DAS181 4.5mg qd x 7 OR 10 days Drug: DAS181 OL (DAS181 4.5mg nebulized qd x 7 OR 10 days ≥ 40kg DAS181 2.5mg nebulized qd x 7 OR 10 days < 40kg)

Trial Centres

Investigators

Download Data (CSV)

Investigator	Centre Name	Trial Centre Country
Aeri Kim akim@ansunbiopharma.com show details		-
Cameron Wolfe, MD	Duke University	USA
Cathy Logan, MD	University of California San Diego Medical Center	USA
Chen Tan, MD	Beth Israel Deaconess Medical Center	USA
Jennifer Ho, M.D 858-452-2631 Ext: 218 jho@ansunbiopharma.com show details	Ansun Biopharma, Inc.	USA
Jonathon Truwit, MD	Froedtert Medical College Pulmonary Clinic	USA
Kathleen Mullane, MD	University of Chicago	USA
Kevin Gregg, MD	Universtiy of Michigan	USA
Kristin Miller, MD	VCU Health System	USA
Medical Monitor 3030 Callan Road San Diego Postcode: CA 92121 United States Telephone: 858452 2631218 Fax: 858452 0133 DAS181@ansunbiopharma.com show details	Ansun Biopharma, Inc.	USA
Rosypriya Kodiyanplakkal, MD	Weill Cornell Medical College	USA
Shmuel Shoham, MD	The Johns Hopkins Hospital	USA
Stanley Lewis, M.D	Ansun Biopharma, Inc.	USA
Stuart Cohen, MD	University of California Davis Health System	USA
Sylvie Lu-Hinh, MS 858-452-2631 Ext: 199 slu-hinh@ansunbiopharma.com show details	Ansun Biopharma, Inc.	USA
Tracy Nguyen 858-452-2631 tnguyen@ansunbiopharma.com show details		-
Yeon Joo Lee, MD	Memorial Sloan Kettering Cancer Center	USA

Centres

Download Data (CSV)

Centre Name	Location	Trial Centre Country
-	-	-
Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago, Illinois	USA
Ansun Biopharma, Inc.	-	-
Ansun Biopharma, Inc.	-	-
Ansun Biopharma, Inc.	San Diego	USA
Asan Medical Center	Songpa-gu, Seoul, Gyeonggi-do	South-Korea
Beth Israel Deaconess Medical Center	Boston, Massachusetts	USA
Brigham and Women's Hospital	Boston, Massachusetts	USA
Children's Hospital Colorado	Aurora, Colorado	USA
Cincinnati Children's Hospital Medical Center	Cincinnati, Ohio	USA
City of Hope cancer Center	Duarte, California	USA
Cook Children's	Fort Worth, Texas	USA
Duke University	Durham, North Carolina	USA
Fred Hutchinson Cancer Research Center	Seattle, Washington	USA
Froedtert Medical College Pulmonary Clinic	Milwaukee, Wisconsin	USA
Hôpital Henri Mondor	Créteil, Ile-de-France	France
Kent Hospital	Warwick, Rhode Island	USA
Louisiana State University	Shreveport, Louisiana	USA
Loyola University Medical Center	Maywood, Illinois	USA
MD Anderson	Houston, Texas	USA
Medical College of Wisconsin	Milwaukee, Wisconsin	USA
Memorial Sloan Kettering Cancer Center	New York, New York	USA
National Cheng Kung University Hospital	North District, Tainan	Taiwan
National Taiwan University Hospital	Zhongzheng, Taipei City	Taiwan
Novant Health	Winston-Salem, North Carolina	USA
Oregon Health & Science University	Portland, Oregon	USA
Peter MacCallum Cancer Centre	Melbourne, Victoria	Australia
Prince of Wales Hospital	Sha Tin, New Territories	Hong-Kong
Rigshospitalet	Copenhagen	Denmark
Royal Melbourne Hospital	Melbourne, Victoria	Australia
Samsung Medical Center	Gangnam-gu, Seoul, Gyeonggi-do	South-Korea
Seattle Children's Hospital	Seattle, Washington	USA
Seoul National University Bundang Hospital	Seongnam-si, Gyeonggi-do	South-Korea
Seoul National University Hospital	Jongno-gu, Seoul, Gyeonggi-do	South-Korea
Shanghai Pulmonary Hospital	Yangpu, Shanghai	China
Shulan (Hangzhou) Hospital co., LTD	Hangzhou, Zhejiang	China
St. Elizabeth Youngstown Hospital	Youngstown, Ohio	USA
Texas Health	Fort Worth, Texas	USA
The Catholic University of Korea, Seoul St. Mary's Hospital	Seocho-gu, Seoul, Gyeonggi-do	South-Korea
The Cleveland Clinic Foundation	Cleveland, Ohio	USA
The First Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou, Zhejiang	China
The Johns Hopkins Hospital	Baltimore, Maryland	USA
The Lindner Center- The Christ Hospital	Cincinnati, Ohio	USA
The Wesley Hospital	Auchenflower, Queensland	Australia
Therapeutic Concepts	Houston, Texas	USA
UCLA	Los Angeles, California	USA
University of California Davis Health System	Sacramento, California	USA
University of California San Diego Medical Center	San Diego, California	USA
University of Chicago	Chicago, Illinois	USA
University of Cincinnati	Cincinnati, Ohio	USA
University of Kansas Medical Center	Fairway, Kansas	USA
University of Maryland	Baltimore, Maryland	USA
University of Nebraska Medical Center	Omaha, Nebraska	USA
University of Pennsylvania	Philadelphia, Pennsylvania	USA
University of Pittsburgh Medical Center Health System	Pittsburgh, Pennsylvania	USA
Universtiy of Michigan	Ann Arbor, Michigan	USA
Vanderbilt University Medical Center	Nashville, Tennessee	USA
VCU Health System	Richmond, Virginia	USA
Washington University	Saint Louis, Missouri	USA
Weill Cornell Medical College	New York, New York	USA
West China Hospital	Chengdu, Sichuan	China
Westmead Hospital	Sydney, New South Wales	Australia

Trial History

Event Date	Event Type	Comment
26 Mar 2021	Other trial event	Last checked against ClinicalTrials.gov record. ClinicalTrials.gov: US National Institutes of Health Updated 26 Mar 2021
23 Mar 2021	Completion date	Planned End Date changed from 28 Dec 2021 to 31 Dec 2023. ClinicalTrials.gov: US National Institutes of Health Updated 26 Mar 2021
17 Feb 2021	Other trial event	Planned number of patients changed from 250 to 274. ClinicalTrials.gov: US National Institutes of Health Updated 23 Feb 2021
21 Jan 2021	Other trial event	This trial is Discontinued in Denmark, according to European Clinical Trials Database record. European Clinical Trials Database Updated 21 Jan 2021
21 Jan 2021	Other trial event	Last checked against European Clinical Trials Database record. European Clinical Trials Database Updated 21 Jan 2021
07 Jan 2021	Other trial event	This trial is Discontinued in France, according to European Clinical Trials Database record. European Clinical Trials Database Updated 07 Jan 2021
14 Jul 2020	Other trial event	According to a Keck Medicine of USC media release, physicians are enrolling patients in this trial. Richard Castriotta, professor of clinical medicine at Keck School of Medicine of USC, is leading the trial for Keck Medicine with fellow researchers Janice Liebler and Aniket Sharma. Updated 17 Jul 2020
26 Mar 2020	Protocol amendment	Patients with COVID -2019 infection were taken additionally to study effect of study drug on COVID-2019 infected patients. No. of arms were changed from 2 to 4. Substudy added in the trial ClinicalTrials.gov: US National Institutes of Health Updated 06 Apr 2020
26 Mar 2020	Other trial event	Planned number of patients changed from 132 to 250. ClinicalTrials.gov: US National Institutes of Health Updated 01 Apr 2020
22 Jan 2020	Other trial event	New source identified and integrated (European Clinical Trials Database: EudraCT2018-004318-16). European Clinical Trials Database Updated 22 Jan 2020
28 Oct 2019	Other trial event	According to a Ansun Biopharma media release the company has raised almost $165,000,000 in the last eighteen months in order to support and fund both the STOP PIV clinical trial and the STOP FLU clinical trial in parallel. Updated 07 Nov 2019
28 Oct 2019	Other trial event	According to an Ansun Biopharma media release, China's National Medical Products Administration has apporved Investigational New Drug Application to enroll patients in China for this study. Updated 07 Nov 2019
28 May 2019	Other trial event	According to an Ansun Biopharma media release, first patient has been enrolled in this study. Updated 30 May 2019
23 May 2019	Status change - recruiting	Status changed from active, no longer recruiting to recruiting. ClinicalTrials.gov: US National Institutes of Health Updated 30 May 2019
21 May 2019	Status change - active, no longer recruiting	Status changed from not yet recruiting to active, no longer recruiting. ClinicalTrials.gov: US National Institutes of Health Updated 24 May 2019
14 Feb 2019	Other trial event	Planned initiation date changed from 28 Feb 2019 to 28 Mar 2019. ClinicalTrials.gov: US National Institutes of Health Updated 22 Feb 2019
23 Jan 2019	Other trial event	New source identified and integrated (ClinicalTrials.gov: NCT03808922). ClinicalTrials.gov: US National Institutes of Health Updated 23 Jan 2019
16 Jan 2019	Status change - not yet recruiting	Status changed from planning to not yet recruiting. ClinicalTrials.gov: US National Institutes of Health Updated 23 Jan 2019
11 Oct 2017	New trial record	New trial record Updated 11 Oct 2017

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