Double Blind, Placebo Controlled Study of Safety and Efficacy of Leronlimab in Patients With "Long" COVID-19

NCT04678830 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CD15_COVID-19
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to assess the safety and efficacy of leronlimab (PRO 140) administered as weekly subcutaneous injections in subjects experiencing prolonged symptoms (\> 12 weeks) of COVID-19.

Conditions

Coronavirus Disease 2019

Keywords

COVID-19

Outcome Measures

Primary Outcomes (1)

• Changes From Baseline in Daily COVID-19-related Symptom Severity Score Through Day 56.

  Changes in common COVID-19-related symptoms were evaluated daily by the patient using a patient diary between start and end of treatment. The diary is shown in Appendix 17.1 in the protocol and covers patient-reported changes for symptoms (ranked as none = 0, mild = 1, moderate = 2 or severe = 3) of cough, sore throat, stuffy or runny nose, difficulty breathing, feeling tightness in chest, feeling fast heartbeat, fatigue, exertional malaise, muscle aches and cramps, muscle weakness, joint pain and swelling, shivering and chills, feeling hot or feverish, difficulty concentrating, insomnia, headache, dizziness, anxiety, tingling or numbness, nausea, vomiting, diarrhea, sense of smell, sense of taste. Maximum score could be 70 (22 parameters with scores up to 3, two parameters with scores up to 2), lowest score could be 0. A negative value shows improvement in symptoms. The lower the value, the greater the improvement (i.e., a score of -16 is greater improvement than a score of -8).

  Changes in COVID-19 related symptoms from baseline (start of treatment) and day 56 (end of treatment)

Secondary Outcomes (8)

• Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary.

  Duration of symptoms from baseline (day 0, start of treatment) and day 56 (end of treatment)

• Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary.

  Between start of treatment (day0) and day 56 (end of treatment)

• Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline.

  Between start of treatment (day0) and day 56 (end of treatment)

• Change From Baseline in PROMIS® Fatigue Score at Days 7,14, 21, 28, 35, 42 and End of Treatment (Day 56).

  Between Baseline (day 0), Visit 4 (day 7), Visit 6 (day 14), Visit 8 (day 21) Visit 10 (day 28), Visit 12 (day 35), Visit 14 (day 42), Visit 16 (Day 56) and Visit 17 (day 56, end of treatment).

• Change From Baseline in PROMIS® Cognitive Function Score at Days 7, 14, 21, 28, 35, 42, 49 and End of Treatment (d56)

  Baseline (start of treatment), day 28 and day 56 (end of treatment)

Other Outcomes (15)

• Change From Baseline in Pulse Oxygen Saturation (SpO2) at Day 7, 14, 21, 28, 35, 42, 49, and 56

  Change between baseline (start of treatment) and Day 7, 14, 21, 28, 35, 42, 49, and 56 (end of treatment).

• Change From Baseline in Serum Cytokine and Chemokine Levels on Days 28 and 56.

  Change between baseline (start of treatment) and days 28 and 56 (end of treatment)

• Change From Baseline in CD4+ and CD8+ T Cell Count on Days 28 and 56.

  Change between baseline (start of treatment) and days 28 and 56 (end of treatment)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Syringes containing normal saline for injection were prepared by an unblinded pharmacist at the clinical sites for use as the placebo.

Drug: Placebos

700mg Leronlimab

EXPERIMENTAL

Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections

Drug: Leronlimab (700mg)

Interventions

Placebos DRUG

Placebos

Also known as: placebo

Placebo

Leronlimab (700mg) DRUG

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

Also known as: Pro140

700mg Leronlimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female adult ≥ 18 years of age at time of enrollment.
• Prior confirmed COVID-19 diagnosis by standard reverse transcriptase-polymerase chain reaction (RT-PCR) assay or equivalent testing
• Clinical Symptom Score of ≥6 AND at least two symptoms of moderate or higher severity as listed below at the time of Screening and currently experiencing two or more of the following symptoms consistent with COVID-19 infection for a prolonged period of time (\>12 weeks).
• Clinical symptoms include the following:
• Respiratory symptoms such as cough, sore throat, stuffy or runny nose, shortness of breath (difficulty breathing), tightness of chest.
• Neurological symptoms such as difficulty in concentration (brain fog), sleep disturbance/insomnia, headache, dizziness, anxiety, tingling or numbness, loss of sense of smell or taste.
• Cardiovascular and Gastrointestinal symptoms such as feeling of fast heartbeat, nausea, vomiting, diarrhea.
• Musculoskeletal symptoms such as muscle aches/cramps, muscle weakness, joint pain/swelling.
• General immune response symptoms such as fatigue (low energy or tiredness), chills or shivering, feeling hot or feverish, or exertional malaise (feeling of discomfort, illness, or lack of well-being after physical activity or mental stress).
• Note: Clinical Symptom Score is obtained from the patient diary (refer to Appendix 1 for scoring instructions).
• Electrocardiogram (ECG) with no clinically significant findings as assessed by the Investigator.
• Note: Below are the examples of clinically significant and non-clinically significant ECG abnormalities:
• ECG findings indicative of acute myocardial infarction or acute ischemic changes would be considered clinically significant abnormalities.
• ECG finding such as atrial fibrillation, atrial flutter, paced rhythms in individuals who have undergone permanent pacemaker placement, evidence of prior infarction, unchanged stable conduction abnormalities e.g. right bundle branch block, or any other finding which does not significantly impact mortality would be considered non-clinically significant findings and subjects with these abnormal findings would be allowed to enroll in the study.
• Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.

You may not qualify if:

• Exhibiting signs of moderate or severe pulmonary disease (such as Chronic Obstructive Pulmonary Disease (COPD), asthma, or pulmonary fibrosis)
• Ongoing requirement of oxygen therapy
• Pulse oxygen saturation (SpO2) of \<94% on room air at the time of screening
• History of splenectomy
• Liver cirrhosis or patient showing signs of clinical jaundice at the time of screening
• Chronic kidney disease stage 4 or requiring dialysis at the time of screening
• New York Heart Association (NYHA) Class III or IV congestive heart failure (CHF)
• Exhibiting signs of uncontrolled hypo-or hyper- thyroidism at the time of Screening
• Uncontrolled rheumatologic disorders at the time of screening
• History of organ transplantation or are candidates for organ transplantation at the time of screening
• History of Chronic Fatigue Syndrome prior to COVID-19 infection
• History of fibromyalgia prior to COVID-19 infection
• History of major psychiatric disorder including bipolar disorders, schizophrenia, schizoaffective disorder, major depression. Patients with major depression can be enrolled if patient has had no episode within the past year or is considered in remission or controlled by treatment.
• Any malignancy within the past 5 years, excluding successfully treated basal cell carcinoma or squamous cell carcinoma without evidence of metastases.
• Any other clinically significant serious systemic diseases which would interfere with study conduct or study results interpretation per the Investigator.

Sponsors & Collaborators

• CytoDyn, Inc.: lead
• Amarex Clinical Research: collaborator

Study Sites (2)

Arthritis & Rheumatic Disease Specialties

Aventura, Florida, 33180, United States

Location

Center for Advanced Research & Education (CARE)

Gainesville, Georgia, 30501, United States

Location

Related Publications (2)

• Gaylis NB, Ritter A, Kelly SA, Pourhassan NZ, Tiwary M, Sacha JB, Hansen SG, Recknor C, Yang OO. Reduced Cell Surface Levels of C-C Chemokine Receptor 5 and Immunosuppression in Long Coronavirus Disease 2019 Syndrome. Clin Infect Dis. 2022 Sep 30;75(7):1232-1234. doi: 10.1093/cid/ciac226.

  PMID: 35452519 DERIVED

• Chang XL, Wu HL, Webb GM, Tiwary M, Hughes C, Reed JS, Hwang J, Waytashek C, Boyle C, Pessoa C, Sylwester AW, Morrow D, Belica K, Fischer M, Kelly S, Pourhassan N, Bochart RM, Smedley J, Recknor CP, Hansen SG, Sacha JB. CCR5 Receptor Occupancy Analysis Reveals Increased Peripheral Blood CCR5+CD4+ T Cells Following Treatment With the Anti-CCR5 Antibody Leronlimab. Front Immunol. 2021 Nov 19;12:794638. doi: 10.3389/fimmu.2021.794638. eCollection 2021.

  PMID: 34868084 DERIVED

Related Links

• PROMIS (Patient-Reported Outcomes Measurement Information System) Fatigue Assessment
• PROMIS (Patient-Reported Outcomes Measurement Information System) Cognitive Function Assessment
• PROMIS (Patient-Reported Outcomes Measurement Information System) Sleep Disturbance Assessment guide
• PROMIS T-score maps

MeSH Terms

Conditions

COVID-19

Interventions

leronlimab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Bernie Cunningham, PhD
• Organization: CytoDyn Inc.

bcunningham@cytodyn.com

(360) 980-8524

Study Officials

• Norman Gaylis, MD

  Arthritis and Rheumatic Disease Specialties Aventura Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2020
• First Posted: December 22, 2020
• Study Start: March 1, 2021
• Primary Completion: June 5, 2021
• Study Completion: July 8, 2021
• Last Updated: April 11, 2024
• Results First Posted: April 11, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)