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A Phase 2b/3, Randomized, Double Blind, Placebo Controlled, Adaptive Design Study to Evaluate the Efficacy and Safety of Leronlimab for Patients With Severe or Critical Coronavirus Disease 2019 (COVID-19)

Trial Profile

A Phase 2b/3, Randomized, Double Blind, Placebo Controlled, Adaptive Design Study to Evaluate the Efficacy and Safety of Leronlimab for Patients With Severe or Critical Coronavirus Disease 2019 (COVID-19)

Status: Recruiting
Phase of Trial: Phase II/III

Latest Information Update: 07 Sep 2020

At a glance

  • Drugs Leronlimab (Primary)
  • Indications COVID 2019 infections
  • Focus Therapeutic Use
  • Sponsors CytoDyn
  • Most Recent Events

    • 02 Sep 2020 According to a CytoDyn media release, an interim analysis on the first 195 patients will be performed in approximately four weeks with results anticipated in mid-October.
    • 02 Sep 2020 According to a CytoDyn media release, in this meeting the company will present a summary of its BLA for HIV in conjunction with our request for fast track approval for COVID-19 indication.
    • 02 Sep 2020 According to a CytoDyn media release, On the suggestion of the MHRA, CytoDyn will submit this study to the Urgent Public Health (UPH) Research scheme to receive possible financial support from the trial sites and the government, if the UPH deems the Company's CD12 trial an urgent health issue.

Trial Overview

Purpose

The purpose of this adaptive design study is to assess the safety and efficacy of leronlimab (PRO 140) administered as weekly subcutaneous injection in subjects with severe or critical COVID-19 disease. The study has three phases lasting 28 days: Screening Period, Treatment Period, and Follow-Up Period.

Comments

According to a CytoDyn media release, the Medicines and Healthcare product Regulatory Agency (MHRA) of the U.K. government requested a meeting with company to discuss the Company's request for Fast Track approval of leronlimab to treat COVID-19 patients with mil-to-moderate symptoms based upon the trial's Top-line Report and additional eIND data. On the suggestion of the MHRA, CytoDyn will submit this study to the Urgent Public Health (UPH) Research scheme to receive possible financial support from the trial sites and the government, if the UPH deems the Company's CD12 trial an urgent health issue.

According to an CytoDyn media release, based on the promising results from the EIND patients, we are hopeful that this randomized, placebo-controlled trial will give us the data needed for FDA approval and ultimately the basis to use leronlimab to save lives in this pandemic.

Primary Endpoints

All-cause mortality at Day 28

description: Day 0 refers to the data of randomization/first treatment.
time_frame: Day 28

Other Endpoints

All-cause mortality at Day 14

description: Day 0 refers to the data of randomization/first treatment.
time_frame: Day 14

Change in clinical status of subject at Day 14 (on a 7 point ordinal scale)

description: A 7-category ordinal scale of patient health status ranges from: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
time_frame: Day 14

Change in clinical status of subject at Day 28 (on a 7 point ordinal scale)

description: A 7-category ordinal scale of patient health status ranges from: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
time_frame: Day 28

Change from baseline in Sequential Organ Failure Assessment (SOFA) score at Day 14.

description: The SOFA score assessment will be based on PaO2/FiO2, platelets, Glasgow coma scale (GCS), bilirubin, Mean arterial pressure OR administration of vasoactive agents required, and Serum creatinine
time_frame: Day 14 [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 390

  • Sex male & female
  • Age Group ≥ 18 years; adult

Patient Inclusion Criteria

1. Male or female adult ≥ 18 years of age at time of screening. 2. Subjects hospitalized with severe or critical illness caused by coronavirus 2019 infection as defined below: A. Severe Illness: - Diagnosed with COVID-19 by standard RT-PCR assay or equivalent testing within 5 days of screening AND Symptoms of severe systemic illness/infection with COVID-19: - At least 1 of the following: fever, cough, sore throat, malaise, headache, muscle pain, shortness of breath at rest or with exertion, confusion, or symptoms of severe lower respiratory symptoms including dyspnea at rest or respiratory distress AND Clinical signs indicative of severe systemic illness/infection with COVID-19, with at least 1 of the following: - RR ≥ 30, HR ≥ 125, SaO2 <93% on room air or requires > 2L oxygen by NC in order maintain SaO2 ≥93%, PaO2/FiO2 <300 AND - None of the following: Respiratory failure (defined by endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula, noninvasive positive pressure ventilation, or clinical diagnosis of respiratory failure in setting of resource limitations), Septic shock (defined by SBP < 90 mm Hg, or Diastolic BP < 60 mm Hg), Multiple organ dysfunction/failure B. Critical Illness: - Diagnosed with COVID-19 by standard RT-PCR assay or equivalent testing within 5 days of screening AND Evidence of critical illness, defined by at least 1 of the following: - Respiratory failure defined based on resource utilization requiring at least 1 of the following: Endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula, noninvasive positive pressure ventilation, ECMO, or clinical diagnosis of respiratory failure (in setting of resource limitation) OR - Shock (defined by SBP < 90 mm Hg, or Diastolic BP < 60 mm Hg or requiring vasopressors) OR -Multiple organ dysfunction/failure 3. Subject, if intubated, positive endexpiratory pressure (PEEP) <15 cmH2O with PaO2/FiO2 >150 mmHg. 4. Electrocardiogram (ECG) with no clinically significant findings as assessed by the Investigator 5. Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures. 6. Understands and agrees to comply with planned study procedures. 7. Women of childbearing potential and their partner must agree to use at least one highly effective method of contraception (e.g., hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], intrauterine devices, bilateral tubal occlusion, or sexual abstinence) for the duration of the study.

Patient Exclusion Criteria

1. Subjects with do-not-resuscitate (DNR) and/or do-not-intubate (DNI) orders or expected to be made DNR/DNI in setting of resource limitations or family wishes. 2. Not a candidate for dialysis or continuation of care (or full medical support) in setting of resource limitations. 3. Subject on continuous vasopressors (at the dose of norepinephrine >20μg/min and/or vasopressin >0.04 units/kg/min) for >48 hours at time of screening. 4. Subjects who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible. 5. Inability to provide informed consent or to comply with test requirements 6. Consideration by the investigator, for safety reasons, that the subject is an unsuitable candidate to receive study treatment 7. Pregnancy or breast feeding 8. Subject participating in another study with for an investigational treatment for COVID-19. Note: Subject who were prescribed (1) hydroxychloroquine or chloroquine with or without azithromycin, (2) Remdesivir, (3) convalescent plasma therapy, or (4) immunomodulatory treatments (including but not limited to sarilumab, clazakizumab, tocilizumab, and anakinra) for the off-label treatment of COVID-19 prior to study enrollment may be included and may continue to receive these agents as part of standard-of-care.

Trial Details

Identifiers

Identifier Owner
NCT04347239 ClinicalTrials.gov: US National Institutes of Health
EudraCT2020-001996-33 European Clinical Trials Database
CD12COVID19 -
CD12 -

Organisations

  • Sponsors CytoDyn
  • Affiliations CytoDyn

Trial Dates

  • Initiation Dates

    Actual : 15 Apr 2020

  • Primary Completion Dates

    Planned : 31 Dec 2020

  • End Dates

    Planned : 01 Apr 2021

Other Details

  • Design double-blind; multicentre; parallel; prospective; randomised
  • Phase of Trial Phase II/III
  • Location United Kingdom; USA
  • Focus Therapeutic Use

Interventions

Drugs Route Formulation
LeronlimabPrimary Drug Subcutaneous Injection

Placebo

Drug: Placebos (Placebos)

700mg Leronlimab

Drug: Leronlimab (700mg) (Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5))

Results

Publications

  1. CytoDyn. Blood Samples at Day 0, 3 and 7 for Severely Ill COVID-19 Patients Clearly Indicate Leronlimab Has Significantly Reduced the Cytokine Storm in All (7) Patients and All Patients Demonstrated Immunological Benefit at Both Day 3 and Day 7. Media-Rel 2020;.

    Media Release

Authors

Author Total Publications First Author Last Author
CytoDyn 1 1 1

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Eric Whitman, MD Atlantic Health System Hospital USA
Harish Seethamraju, MD Montefiore Medical Center USA
Jordan Lake, MD University of Texas USA
Kiran Devulapally, MD Ohio Health USA
Kush Dhody, MBBS, MS, CCRA
301-956-2536 kushd@amarexcro.com
show details
-
Marcel Curlin, MD Oregon Health and Sciences University USA
Michael Morgan, MD Novant Health USA
Nancy Lopez
310-794-8043 NancyRLopez@mednet.ucla.edu
show details
UCLA USA
Onyema Ogbuagu, MD Yale USA
Otto Yang, MD UCLA USA
Pailing Richards
704-996-7627 pcrichards@novanthealth.org
show details
Novant Health USA
Reena Joseph
718-920-5864
show details
Montefiore Medical Center USA
Sabrina Tan, MD Beth Israel, Harvard USA
Shahriyar Tavakoli, MD Eisenhower Health USA
Subroto Paul, MD St. Barnabas USA

Centres

Centre Name Location Trial Centre Country
-
-
-
Atlantic Health System Hospital Morristown, New Jersey USA
Beth Israel, Harvard Boston, Massachusetts USA
CytoDyn, Inc.
-
-
Eisenhower Health Rancho Mirage, California USA
Montefiore Medical Center Bronx, New York USA
Novant Health Winston-Salem, North Carolina USA
Ohio Health Cleveland, Ohio USA
Oregon Health and Sciences University Portland, Oregon USA
St. Barnabas Livingston, New Jersey USA
UCLA Los Angeles, California USA
University of Texas Houston, Texas USA
Yale New Haven, Connecticut USA

Trial History

Event Date Event Type Comment
07 Sep 2020 Other trial event New source identified and integrated(European Clinical Trials Database;EudraCT2020-001996-33). Updated 07 Sep 2020
02 Sep 2020 Other trial event According to a CytoDyn media release, an interim analysis on the first 195 patients will be performed in approximately four weeks with results anticipated in mid-October. Updated 04 Sep 2020
02 Sep 2020 Other trial event According to a CytoDyn media release, in this meeting the company will present a summary of its BLA for HIV in conjunction with our request for fast track approval for COVID-19 indication. Updated 04 Sep 2020
02 Sep 2020 Other trial event According to a CytoDyn media release, On the suggestion of the MHRA, CytoDyn will submit this study to the Urgent Public Health (UPH) Research scheme to receive possible financial support from the trial sites and the government, if the UPH deems the Company's CD12 trial an urgent health issue. Updated 04 Sep 2020
02 Sep 2020 Other trial event According to a CytoDyn media release, the Medicines and Healthcare product Regulatory Agency (MHRA) of the U.K. government requested a meeting with company to discuss the Company's request for Fast Track approval of leronlimab to treat COVID-19 patients with mil-to-moderate symptoms based upon the trial's Top-line Report and additional eIND data. Updated 04 Sep 2020
01 Sep 2020 Other trial event Last checked against Clinicaltrials.gov record. Updated 01 Sep 2020
25 Aug 2020 Other trial event According to a CytoDyn media release, the company has reached the requisite number of enrolled patients i.e 195 in this study to perform an interim analysis following the 28-day phase of the trial. Interim analysis to commence after 28 days with results anticipated by mid-October 2020. Updated 27 Aug 2020
20 Aug 2020 Other trial event According to a CytoDyn media release, the MHRAs decision follows several months of its review of CytoDyns manufacturing processes and leronlimabs safety profile. Patient enrollment to commence immediately. Updated 25 Aug 2020
20 Aug 2020 Other trial event According to a CytoDyn media release, the company announced today that the Clinical Trials Unit of the Medicines & Healthcare product Regulatory Agency (MHRA) of the U.K. government authorized the Company to enroll for this ongoing Phase 3 COVID-19 trial in the United Kingdom. Updated 25 Aug 2020
19 Aug 2020 Other trial event According to a Cytodyn media release, enrollment is now at 182 and the company anticipates enrollment will reach 195 by the end of August. Updated 25 Aug 2020
04 Aug 2020 Other trial event According to a Cytodyn media release, this study has currently enrolled 169 patients and the Company will conduct a full interim analysis once 195 patients are enrolled. Updated 07 Aug 2020
04 Aug 2020 Other trial event According to a CytoDyn media release, the independent Data Safety Monitoring Committee (DSMC) completed its first safety review (n=149 subjects), and reported it saw no cause to modify the study. Updated 07 Aug 2020
13 Jul 2020 Other trial event According to a CytoDyn media release, periodic safety review by Data Safety Monitoring Committee (DSMC) for ongoing Phase 3 study (severe/critical population) is planned for next week. Results is expected to be announced in July. Updated 17 Jul 2020
11 Jun 2020 Other trial event According to an CytoDyn media release, the company will do an interim analysis of patient data in this Phase 3 trial for severe and critically ill COVID-19 patients and hope to have important results in 2 to 3 weeks. Updated 15 Jun 2020
22 May 2020 Other trial event According to a CytoDyn media release, the company will hold conference call to provide updates on COVID-19 (Phase 2, 3 & eIND) on Tuesday, May 26, 2020. Updated 26 May 2020
21 May 2020 Other trial event According a Montefiore media release, this trial is conducted under the direction of the departments of cardiothoracic surgery and medicine at Montefiore Health System and Albert Einstein College of Medicine Updated 24 May 2020
07 May 2020 Other trial event According to an CytoDyn media release, Novant Health is initiating patient enrollment in CytoDyns Phase 2b/3 trial for severely and critically ill COVID-19 patients. Updated 11 May 2020
05 May 2020 Other trial event According to an Ajinomoto Bio-Pharma Services, the company has entered into a manufacturing services agreement with CytoDyn Inc., for the supply of the investigational new drug, leronlimab (PRO 140), which is currently being used in clinical trial protocols for Mild-to-Moderately Ill (NCT04343651) and Severely Ill (NCT04347239) COVID-19 patients. Updated 06 May 2020
29 Apr 2020 Other trial event According to a CytoDyn media release, Dr. Nader Pourhassan, will provide a comprehensive update on leronlimab for COVID-19. The Wall Street Reporters event is scheduled for Friday, May 1, 2020 at 12:30 pm ET / 9:30 am PT.Access:https://register.gotowebinar.com/register/8835183266170118926Dr. Pourhassan will provide an update on patient enrollment in eIND, Phase 2 and Phase 2b/3 COVID-19 trials Updated 04 May 2020
17 Apr 2020 Other trial event New source identified and integrated: (ClinicalTrials.gov: US National Institutes of Health: NCT04347239). Updated 17 Apr 2020
16 Apr 2020 Other trial event According to a CytoDyn media release, Dr.Nader Pourhassan, will discuss about two trials (NCT04347239 and NCT04343651) at Wall Street Reporters NEXT SUPER STOCK Livestream event. Updated 18 May 2020
15 Apr 2020 Other trial event According to an CytoDyn media release, About 30 patients have been administered leronlimab under Emergency Investigational New Drug (EIND) authorizations granted by the U.S. Food and Drug Administration (FDA) Updated 20 Apr 2020
15 Apr 2020 Other trial event According to an CytoDyn media release, Based on the promising results from the EIND patients, we are hopeful that this randomized, placebo-controlled trial will give us the data needed for FDA approval and ultimately the basis to use leronlimab to save lives in this pandemic Updated 17 Apr 2020
15 Apr 2020 Other trial event According to an CytoDyn media release, Patients enrolled in this trial are expected to be administered leronlimab for two weeks Updated 17 Apr 2020
15 Apr 2020 Other trial event According to an CytoDyn media release, the treatment of the first patient with leronlimab is done in its Phase 2b/3 trial for severe and critical COVID-19 indications Updated 17 Apr 2020
13 Apr 2020 Other trial event According to an CytoDyn media release, First site has been cleared to enroll patients in this study beginning today. Updated 14 Apr 2020
09 Apr 2020 Protocol amendment According to a Cytodyn media release, the study protocol was revised with change in duration of primary endpoint from 14 days to 28 days and change in planned enrollment from 342 to 390. Updated 13 Apr 2020
09 Apr 2020 Other trial event Planned number of patients changed from 342 to 390, according to a Cytodyn media release. Updated 13 Apr 2020
09 Apr 2020 Results Results published in the Cytodyn media release Updated 13 Apr 2020
07 Apr 2020 New trial record New trial record Updated 07 Apr 2020
06 Apr 2020 Other trial event According to a Cytodyn media release,the Company will perform an interim analysis on the data from 50 patients following two weeks of leronlimab therapy. Updated 07 Apr 2020
01 Apr 2020 Other trial event According to a Cytodyn media release, the company expects to enroll patients in this study and a phase II study, very quickly under the same IND that was provided with a safe to proceed letter from the FDA. Updated 07 Apr 2020
01 Apr 2020 Other trial event According to a Cytodyn media release, the company has filed a second clinical trial protocol with the U.S. Food and Drug Administration (FDA) to treat severely ill COVID-19 patients with leronlimab. This trial will be conducted under the same FDA-approved IND as the Company recently initiated Phase 2 clinical trial ( CTP 319302) to treat COVID-19 patients with mild-tomoderate indications Updated 07 Apr 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
  2. CytoDyn. CytoDyn's Drs. Pourhassan and Patterson to Present Live at Wall Street Reporter's Event to Discuss Paper Recently Submitted for Publication and Positive Results of eIND COVID-19 Patients. Media-Rel 2020;.

    Media Release
  3. CytoDyn. CytoDyn Receives Positive DSMC Recommendation for Leronlimab Phase 3 COVID-19 Trial with No Safety Concerns. Media-Rel 2020;.

    Media Release
  4. CytoDyn. After Several Months of Providing Requested Information About Manufacturing and Safety of Leronlimab, U.K.'s MHRA Accepts CytoDyn's Request to Enroll in its Current Phase 3 Trial for COVID-19 Patients with Severe-to-Critical Symptoms. Media-Rel 2020;.

    Media Release
  5. CytoDyn. Update on HIV-BLA-PDUFA: FDA requested more information to complete a substantive review. No additional trials required. CytoDyn plans to submit the requested information and will ask for a Type A meeting with the FDA per the agency's suggestion. Media-Rel 2020;.

    Media Release
  6. CytoDyn. CytoDyn to Hold Conference Call to Provide Updates on COVID-19 (Phase 2, 3 & eIND), Cancer (mTNBC, Phase 2 for 22 Solid Tumor Cancers), HIV (BLA, Monotherapy), NASH, GvHD and MS. Media-Rel 2020;.

    Media Release
  7. CytoDyn. Severely Ill COVID-19 Patient at Leading Southern California Medical Center Extubated Three Days After Treatment with CytoDyn's Leronlimab; Two Moderate COVID-19 Patients Removed from External Oxygen Following One Day of Treatment with Leronlimab and Discharged from Hospital. Media-Rel 2020;.

    Media Release
  8. European Clinical Trials Database. Trial-Reg 2016;.

    Available from: URL: https://www.clinicaltrialsregister.eu
  9. CytoDyn. CytoDyn Reached Its Enrollment Target for Phase 2 COVID-19 Trial for Mild to Moderate Indication Primary End Point Announcement Is Next. Media-Rel 2020;.

    Media Release
  10. CytoDyn. U.K. MHRA Grants Meeting to CytoDyn to Discuss Fast Track Approval of Leronlimab for COVID-19 Patients. Media-Rel 2020;.

    Media Release
  11. CytoDyn. CytoDyn Files a Clinical Trial Protocol with the FDA to Treat Severely Ill COVID-19 Patients with Leronlimab where the Primary Endpoint is Mortality Rate at Two Weeks. Media-Rel 2020;.

    Media Release
  12. CytoDyn. CytoDyn Requests ##8220##Fast Track Approval##8221## for COVID-19 Patients from U.K.'s Regulatory Agency MHRA based on its Top-line Report Showing Statistically Significant Endpoint, NEWS2 (p < 0.023) and Notable Safety Results. Media-Rel 2020;.

    Media Release
  13. CytoDyn. Novant Health Initiates Phase 2b/3 Trial with CytoDyn's Leronlimab for Severely and Critically Ill COVID-19 Patients. Media-Rel 2020;.

    Media Release
  14. CytoDyn. CytoDyn Reaches Enrollment of 195 Patients in its Phase 3 Trial for COVID-19 Patients with Severe-to-Critical Symptoms. Media-Rel 2020;.

    Media Release
  15. CytoDyn. First Two Patients Enrolled in Randomized Phase 2, COVID-19 Trial with Leronlimab; Five More Severely Ill COVID-19 Patients Treated Under Emergency IND and Two Patients Have Already Extubated. Media-Rel 2020;.

    Media Release
  16. CytoDyn. CytoDyn to Present at Wall Street Reporter's ##8220##NEXT SUPER STOCK##8221## Livestream Event on April 17, 2020 at 12:30 pm ET / 9:30 am PT. Media-Rel 2020;.

    Media Release
  17. CytoDyn. Southern California Patients Treated with Leronlimab for COVID-19 under Emergency IND: 4 Patients with Moderate Indications Removed from Oxygen; 3 Patients Discharged from Hospital; 1 Patient Scheduled for Discharge Today; 1 Patient with Severe Indications Discharged, for Total of 5 Patients Discharged. Media-Rel 2020;.

    Media Release
  18. Ajinomoto BioPharma Services. Ajinomoto Bio-Pharma Services Announces Manufacturing Partnership with CytoDyn for Drug Product Used in COVID-19 Clinical Trials. Media-Rel 2020;.

    Media Release
  19. Montefiore Health System. A Promising Drug for the Treatment of Severe Lung Inflammation in COVID-19 Patients: Montefiore-Einstein Scientists Lead Two Trials of Leronlimab. Media-Rel 2020;.

    Media Release
  20. CytoDyn. Blood Samples at Day 0, 3 and 7 for Severely Ill COVID-19 Patients Clearly Indicate Leronlimab Has Significantly Reduced the Cytokine Storm in All (7) Patients and All Patients Demonstrated Immunological Benefit at Both Day 3 and Day 7. Media-Rel 2020;.

    Media Release
  21. CytoDyn. First Patient Treated with Leronlimab in Phase 2b/3 Trial for COVID-19. Media-Rel 2020;.

    Media Release
  22. CytoDyn. Treatment with CytoDyn's Leronlimab Indicates Significant Trend Toward Immunological Restoration in Severely Ill COVID-19 Patients. Media-Rel 2020;.

    Media Release
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