COVID-19 Long-Haulers Study

• ClinicalTrials.gov Identifier: NCT04678830
• Recruitment Status: Recruiting
• First Posted: December 22, 2020
• Last Update Posted: March 5, 2021
• Sponsor: CytoDyn, Inc.
• Collaborator: Amarex Clinical Research
• Information provided by (Responsible Party): CytoDyn, Inc.

Study Description

Brief Summary:

The purpose of this study is to assess the safety and efficacy of leronlimab (PRO 140) administered as weekly subcutaneous injection in subjects experiencing prolonged symptoms (> 6 weeks) of COVID-19.

Condition or disease	Intervention/treatment	Phase
Coronavirus Disease 2019	Drug: Placebos; Drug: Leronlimab (700mg)	Phase 2

Detailed Description:

This is a Phase 2, two-arm, randomized, double blind, placebo controlled multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with prolonged symptoms caused by COVID-19. Patients will be randomized to receive weekly doses of 700 mg leronlimab (PRO 140), or placebo. Leronlimab (PRO 140) and placebo will be administered via subcutaneous injection.

The study will have three phases: Screening Period, Treatment Period, and Follow-Up Period. Total study duration is 91 weeks. The study will be conducted at up to 5 centers in the United States and planned number of subjects are 50 subjects.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, 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]
• Actual Study Start Date: March 1, 2021
• Estimated Primary Completion Date: June 23, 2021
• Estimated Study Completion Date: July 23, 2021

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo	Drug: Placebos; Placebos
Experimental: 700mg Leronlimab	Drug: Leronlimab (700mg); Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)

Outcome Measures

Primary Outcome Measures :

1. Changes from baseline in daily COVID-19-related symptom severity score through Day 56. [ Time Frame: Day28 ]
   Note: A set of common COVID-19-related symptoms (see patient diary template) will be evaluated daily by the patient regardless of which symptoms a subject had at baseline, as new symptoms may appear following the baseline assessment.

Secondary Outcome Measures :

1. Duration of COVID-19 associated symptoms from start of study treatment (Day 0) based on self-assessment using daily symptom diary. [ Time Frame: 56 days ]

   Duration is defined as number of days when any symptoms scored as

   • moderate or severe at baseline are still scored as moderate or severe (i.e., not mild or absent) through Day 56, or
   • mild or absent at study entry are scored as mild or worse (i.e., not absent)through Day 56.
2. Number of symptom-free days of COVID-19 associated symptoms that were present at the start of study treatment (Day 0) based on self-assessment using daily symptom diary. [ Time Frame: 56 days ]
   Symptom-free days are defined as number of days when any symptoms scored as mild, moderate or severe at baseline are scored as absent (or none) through Day 56.
3. Progression (or worsening) of COVID-19-associated symptoms through Day 56 compared to baseline. [ Time Frame: 56 days ]

   Progression or symptom worsening is defined as number of days when any symptoms scored as

   • moderate at baseline are scored as severe through Day 56.
   • mild at baseline are scored as moderate or severe through Day 56.
   • absent at baseline are scored as mild, moderate or worse through Day 56.
4. • Change from baseline in PROMIS® Fatigue Score at Days 28 and 56 and 56. [ Time Frame: Days 42 and 56 ]
5. Change from baseline in PROMIS® Cognitive Function Score at Days 28 and 56 [ Time Frame: Days 42 and 56 ]
6. Change from baseline in PROMIS® Sleep Disturbance Score at Days 28 and 56. [ Time Frame: Days 42 and 56 ]
7. Duration (days) of hospitalization during the treatment phase [ Time Frame: 56 days ]
8. Incidence of hospitalization during the treatment phase [ Time Frame: 56 days ]

Other Outcome Measures:

1. Change from baseline in pulse oxygen saturation (SpO2) at Day 7, 14, 21, 28, 35, 42, 49, and 56 [ Time Frame: Day 7, 14, 21, 28, 35, 42, 49, and 56. ]
   Exploratory Outcome
2. Change from baseline in serum cytokine and chemokine levels [ Time Frame: 56 days ]
   Exploratory Outcome
3. Change from baseline in CD4+ and CD8+ T cell count [ Time Frame: 56 days ]
   Exploratory Outcome
4. Change from baseline in Transgrowth factor beta 1 (TGF beta1) on Days 14, 28, 42, and 56 [ Time Frame: Days 14, 28, 42, and 56 ]
   Exploratory Outcome
5. Change from baseline in CRP on Days 14, 28, 42, and 56 [ Time Frame: Days 14, 28, 42, and 56 ]
   Exploratory Outcome
6. Incidence of treatment-related adverse events (TEAEs) [ Time Frame: 91 days ]
   Safety Measures
7. Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: 91 days ]
   Safety Measures
8. Incidence of serious adverse events (SAEs) [ Time Frame: 91 days ]
   Safety Measures
9. Incidence of TEAEs and SAEs leading to discontinuation of study medication. [ Time Frame: 56 days ]
   Safety Measures
10. Changes in blood chemistry, hematology and coagulation parameter results [ Time Frame: 91 days ]
    Safety Measures
11. Changes in vital signs including temperature, pulse, respiratory rate, systolic and diastolic blood pressure [ Time Frame: 91 days ]
    Safety Measures
12. Changes in physical examination results [ Time Frame: 91 days ]
    Safety Measures
13. Changes in electrocardiogram (ECG) results [ Time Frame: 91 days ]
    Safety Measures

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or female adult ≥ 18 years of age at time of enrollment.
2. Prior confirmed COVID-19 diagnosis by standard RT-PCR assay or equivalent testing

3. 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 etc.
   • 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 etc.
   • Cardiovascular and Gastrointestinal symptoms such as feeling of fast heartbeat, nausea, vomiting, diarrhea, etc.
   • 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, other flu-like symptoms, or exertional malaise (feeling of discomfort, illness, or lack of well-being after physical activity or mental stress).

4. 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.
5. Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
6. Men and women of childbearing potential and their partner must agree to use two medically accepted methods of contraception (e.g., barrier contraceptives [male condom, female condom, or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], or one of the following methods of birth control (intrauterine devices, bilateral tubal occlusion, or vasectomy) or must practice complete sexual abstinence for the duration of the study (excluding women who are not of childbearing potential and men who have been sterilized).
7. Females of child-bearing potential must have a negative urine pregnancy test at Screening Visit and prior to receiving the first dose of study drug; and Male participants must agree to use contraception and refrain from donating sperm for at least 90 days after the last dose of study intervention.
8. Subject is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures and study restrictions

Exclusion Criteria:

1. Exhibiting signs of moderate or severe pulmonary disease (such as COPD, asthma, or pulmonary fibrosis)
2. Ongoing requirement of oxygen therapy
3. Pulse oxygen saturation (SpO2) of <94% on room air at the time of screening
4. History of splenectomy
5. Liver cirrhosis or patient showing signs of clinical jaundice at the time of screening
6. Chronic kidney disease stage 4 or requiring dialysis at the time of screening
7. NYHA Class III or IV congestive heart failure (CHF)
8. Exhibiting signs of uncontrolled hypo-or hyper- thyroidism at the time of Screening
9. Uncontrolled rheumatologic disorders at the time of screening
10. History of organ transplantation or are candidates for organ transplantation at the time of screening
11. History of Chronic Fatigue Syndrome prior to COVID-19 infection
12. History of fibromyalgia prior to COVID-19 infection
13. 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.
14. Any malignancy within the past 5 years, excluding successfully treated basal cell carcinoma or squamous cell carcinoma without evidence of metastases.
15. Any other clinically significant serious systemic diseases which would interfere with study conduct or study results interpretation per the Investigator.
16. Treatment with immunosuppressive or immunomodulatory medications within 5 half-lives prior to screening. Patients on replacement therapy for adrenal insufficiency will be allowed. Patients on stable (> 3 months) low dose corticosteroid ≤ 5 mg Prednisone will be allowed.
17. History of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible
18. Ongoing use of CCR5 antagonist
19. Inability to provide informed consent or to comply with test requirements
20. Consideration by the investigator, for safety reasons, that the subject is an unsuitable candidate to receive study treatment
21. Pregnancy or breast feeding
22. Participating in another study for an investigational treatment

Contacts and Locations

Contacts

Contact: Kush Dhody, MBBS, MS, CCRA; 240-454-6843; kushd@amarexcro.com

Locations

United States, Florida

Arthritis & Rheumatic Disease Specialties; Not yet recruiting

Aventura, Florida, United States, 33180

Contact: Joanne Sagliani 305-932-4162 jsagliani@aol.com

United States, Georgia

Center for Advanced Research & Education (CARE); Recruiting

Gainesville, Georgia, United States, 30501

Contact: Julie Recknor jrecknor@carega.net

Principal Investigator: Angela Ritter

Sponsors and Collaborators

CytoDyn, Inc.

Amarex Clinical Research

More Information

• Responsible Party: CytoDyn, Inc.
• ClinicalTrials.gov Identifier: NCT04678830
• Other Study ID Numbers: CD15_COVID-19
• First Posted: December 22, 2020
• Last Update Posted: March 5, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by CytoDyn, Inc.:

COVID-19

Additional relevant MeSH terms:

Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases