Leronlimab independent Data Safety Monitoring Committee Glimpse at Data: Phase 3 Study Proceeds

Leronlimab independent Data Safety Monitoring Committee Glimpse at Data Phase 3 Study Proceeds

CytoDyn Inc. a late-stage biotechnology company disclosed that an independent Data Safety Monitoring Committee (“DSMC”), completed its first safety review of the ongoing Phase 3 clinical trial (CD12) in patients with severe and critical COVID-19 and reported it saw no case to modify the study. This particular DSMC reviewed compiled data from 149 subjects enrolled in the CD12 trial. Because no safety concerns were raised, the trial continues. TrialSite has reported that Leronlimab has demonstrated promise with an ability to apparently inhibit lung inflammation associated with COVID-19.

Phase 2b/3 Leronlimab Study

The Phase 2b/3, two-arm, randomized, double blind, placebo controlled, adaptive design multicenter study ongoing evaluates the safety and efficacy of leronlimab (PRO140) in patients with severe or critical symptoms of respiratory illness caused by COVID-19. Patients are randomized to receive weekly doses of 700 mg leronlimab (PRO 14), or placebo.  Leronlimab (PRO 140) and placebo are administered via subcutaneous injection. The study includes three phases including 1) Screening Period, 2) Treatment Period and 3) Follow-up Period.

The protocol called for 390 participants and presently the reports are 169 participants in the Phase 3 effort. The study commenced in April and runs through to estimated primary completion date of December 31, 2020 and estimated study completion date of April 1, 2021. The Phase 3 study will conduct a full interim analysis once 195 participants are enrolled, as provided in the trial protocol.

CD12 is a Phase 3 randomized, double blind, placebo controlled, adaptive design multicenter two arm study to evaluate the safety and efficacy of leronlimab in patients with severe or critical symptoms of respiratory illness caused by coronavirus 2019 infection. Patients are randomized 2:1 (two leronlimab: one placebo) to receive weekly doses of 700 mg leronlimab or placebo via subcutaneous injection. The study has three phases: Screening Period, Treatment Period and Follow-Up Period. The primary outcome measured by this study is: all-cause mortality at Day 28. Secondary outcomes measured are: (1)  all-cause mortality at Day 14, (2)  change in clinical status of subject at Day 14, (3) change in clinical status of subject at Day 28, and (4) change from baseline in Sequential Organ Failure Assessment (SOFA) score at Day 14.

CEO Comment

Nader Pourhassan, PhD, President and Chief Executive Officer of CytoDyn, reported that the sponsor was less than 30 patients from their planned interim analysis enrollment target. They hope to share the interim efficacy results “as soon as possible.


The study is being managed by contract research organization (CRO) Amarex, an NSF International company. Amarex Clinical Research is based in Germantown, MD, and in 2019 was acquired by NSF InternationalNSF International is an American-based multinational testing company.

The Investigational Product

The FDA has granted a Fast Track designation to CytoDyn for two potential indications of leronlimab for critical illnesses. The first as a combination therapy with HAART for HIV-infected patients and the second is for metastatic triple-negative breast cancer. Leronlimab is an investigational humanized IgG4 mAb that blocks CCR5, a cellular receptor that is important in HIV infection, tumor metastases, and other diseases, including NASH. Leronlimab has completed nine clinical trials in over 800 people and met its primary endpoints in a pivotal Phase 3 trial (leronlimab in combination with standard antiretroviral therapies in HIV-infected treatment-experienced patients). 

In regards of HIV/AIDS, leronlimab is a viral-entry inhibitor; it masks CCR5, thus protecting healthy T cells from viral infection by blocking the predominant HIV (R5) subtype from entering those cells. Leronlimab has been the subject of nine clinical trials, each of which demonstrated that leronlimab could significantly reduce or control HIV viral load in humans. The leronlimab antibody appears to be a powerful antiviral agent leading to potentially fewer side effects and less frequent dosing requirements compared with daily drug therapies currently in use. 

In the setting of cancer, research has shown that CCR5 may play a role in tumor invasion, metastases, and tumor microenvironment control. Increased CCR5 expression is an indicator of disease status in several cancers. Published studies have shown that blocking CCR5 can reduce tumor metastases in laboratory and animal models of aggressive breast and prostate cancer. Leronlimab reduced human breast cancer metastasis by more than 98% in a murine xenograft model. CytoDyn is, therefore, conducting a Phase 1b/2 human clinical trial in metastatic triple-negative breast cancer and was granted Fast Track designation in May 2019.  

The CCR5 receptor appears to play a central role in modulating immune cell trafficking to sites of inflammation. It may be crucial in the development of acute graft-versus-host disease (GvHD) and other inflammatory conditions. Clinical studies by others further support the concept that blocking CCR5 using a chemical inhibitor can reduce the clinical impact of acute GvHD without significantly affecting the engraftment of transplanted bone marrow stem cells. CytoDyn is currently conducting a Phase 2 clinical study with leronlimab to support further the concept that the CCR5 receptor on engrafted cells is critical for the development of acute GvHD, blocking the CCR5 receptor from recognizing specific immune signaling molecules is a viable approach to mitigating acute GvHD. The FDA has granted “orphan drug” designation to leronlimab for the prevention of GvHD. 

Sites & Principal Investigators

The critical CD12 trial involves the following sites and principal investigators

Research SitePrincipal Investigator
UCLA, LA CAOtto Yang, MD
Eisenhower HealthShahriyar Tavakoli, MD
YaleOnyema Ogbuagu, MD
Beth Israel Deaconess Medical CenterSabrina Tan, MD
St. BarnabasSubroto Paul, MD
Atlantic Health System HospitalEric Whitman, MD
Montefiore Medical CenterHarish Seethanraju, MD
Novant HealthMichael Morgan, MD
Ohio HealthKiran Devulapally, MD
Oregon Health and Science UniversityMarcel Curlin, MD
Baylor Scott & WhiteUriel Sandkovsky, MD
University of TexasJordan Lake, MD

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