Protocol Filed With FDA for Phase 2 Trial of Leronlimab to Treat Long-Hauler Symptoms of COVID-19

A protocol has been filed with the FDA for a phase 2 clinical trial aimed to evaluate leronlimab (PRO 140), which has been used to treat various solid tumors and hematologic malignancies, as treatment of patients with coronavirus disease 2019 (COVID-19) who are suffering from long-hauler symptoms, according to a press release from CytoDyn Inc., developer of the drug.

The CCR5 antagonist will be evaluated in 102 patients enrolled in up to 10 sites, according to the protocol for the study, entitled, “A Randomized, Double Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Leronlimab in Patients Experiencing Prolonged Coronavirus Disease 2019 (COVID-19) Symptoms [Long-Haulers].” The study will include an interim analysis after half the patients are enrolled and will allow CytoDyn to report the data.

The therapeutic benefit of leronlimab in patients with COVID-19 has been demonstrated in another recent study, the phase 2 CD10 clinical trial of leronlimab for mild-to-moderate COVID-19.

“We are very pleased to be able to finalize this protocol and submit today. Many thanks to Drs. Chris Recknor, Mahboob Rahman, and Kush Dhody for spending countless hours over the last 6 weeks finalizing this very challenging trial protocol. Dr. Recknor’s past enrollment of patients in our CD10 trial was critical to his understanding of what leronlimab can do and his experience with those patients greatly assisted us to design and finalize this protocol,” said Nader Pourhassan, PhD, president and chief executive officer of CytoDyn, in a statement.

About 10% of patients with COVID-19 have become long-haulers, and published studies and surveys have indicated that 50% to 80% of patients continue having troublesome symptoms 3 months after onset of the virus, even lasting later than when tests can detect the virus in the body. Long-hauler symptoms form an extensive and inconsistent list as for some people, lingering symptoms are nothing like the original symptoms when they were first infected. The most common long-hauler symptoms include coughing; ongoing, sometimes debilitating, fatigue; body aches; joint pain; heart issues; shortness of breath; loss of taste and smell; difficulty sleeping; headaches; and brain fog.

“If successful, this phase 2 trial could potentially allow leronlimab to be the first treatment for patients experiencing these debilitating symptoms and perhaps their only hope for full recovery,” Pourhassan stated. “We have become very knowledgeable of leronlimab’s potential for COVID-19 patients due to our completed phase 2 trial for mild-to-moderate symptoms, for which a complete report has been submitted to a very reputable journal for publication.”

The phase 2 CD10 clinical trial was a double-blinded randomized study of leronlimab as treatment of patients with mild-to-moderate COVID-19, and the agent induced statistically significant findings with a reduction in the National Early Warning Score 2 (NEWS2) at day 14. The findings were recently shared during a presentation during the Special isirv-Antiviral Group Conference on ‘Therapeutics for COVID-19’ and demonstrated its potential to prevent progression to severe or critical disease.²

In the CD10 study, no differences in oxygen use or hospitalizations were observed between the leronlimab and placebo arms, although this may have been limited due to exclusion of patients with pre-existing medical conditions, such as severe pulmonary, liver, and renal disease who have been to be at higher risk of COVID-19 progression and overall mortality.

The Total Symptom Score at baseline was ≤4 in 53.6% of patients and >4 in 46.4%. Most patients (76.2%) did not receive any off-label COVID-19 treatments, and 61.9% were aged <60 years, and the majority (66.7%) had never smoked.

In terms of toxicity, adverse events (AEs) of any grade were seen in 33 patients (39.3%), while mild events occurred in 17 (20.2%), moderate in 8 (9.5%), and severe in 8 (9.5%). incidence, frequency, and severity of AEs were lower with leronlimab compared with placebo, in which AEs of any grade were observed in 19 patients (33.9%) versus 14 (50.0%), of mild severity in 12 (21.4%) versus 5 (17.9%), moderate in 2 (3.6%) versus 6 (21.4%), and severe in 5 (8.9%) versus 3 (10.7%), respectively. Eight serious AEs occurred in 56 patients (14%) in the leronlimab arm compared with 11 in 28 patients (39%) from the placebo arm.

Overall 11 patients (13.1%) experienced treatment-emergent AEs (TEAEs), including 5 (8.9%) in the leronlimab and 6 (21.4%) in the placebo arm. TEAEs that were possibly related to study treatment were observed in 2 patients (7.1%) of patients in the placebo arm versus none in the chemotherapy arm. TEAEs that were unrelated to the study treatment were observed in 5 patients (8.9%) who received leronlimab versus 4 (14.3%) in the placebo arm.

A phase 2b/3 randomized study from CytoDyn is currently enrolling patients with severe-to-critically ill COVID-19 across several hospitals in the United States to be treated with leronlimab, and an interim analysis was conducted on the first 195 patients in mid-October. Another analysis will be performed when 293 patients are enrolled in the study.¹

_References

_{1. Cytodyn Files Protocol with U.S. FDA for Phase 2 Clinical Trial for COVID-19 Patients with Long-Hauler Symptoms. News Release. CytoDyn Inc. November 17, 2020. Accessed November 23, 2020. https://bit.ly/2HuucTP}

_{2. Seethamraju H, Recknor C, Otto Y, et al. A Phase 2 Study of Leronlimab for Mild to Moderate Coronavirus Disease 2019 (COVID-19). Presented during: Antiviral Group virtual Conference on ‘Therapeutics for COVID-19’; October 6-8, 2020; Virtual.}