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

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]

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.

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 Coronavirus Disease 2019 (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 days. The study will be conducted at up to 5 centers in the United States and planned number of subjects are 50 subjects.

Visit schedule:

Visit 1 - Screening assessment Visit 2 - baseline, first dose Visit 3 - no dose, baseline+3 days Visit 4 - second dose, baseline + 7 days Visit 5 - no dose, safety assessment/con med, baseline +10 days Visit 6 - third dose, baselines + 14 days Visit 7 - no dose, safety assessments, baseline + 17 days Visit 8 - fourth dose, baseline +21 days Visit 9 - no dose, safety assessment, baseline + 24 days Visit 10 - fifth dose, baseline + 28 days Visit 11 - no dose, safety assessment, baseline + 31 days Visit 12 - sixth dose, baseline + 35 days Visit 13 - no dose, safety assessment, baseline + 38 days Visit 14 - seventh dose, baseline + 42 days Visit 15 - no dose, safety assessment, baseline + 45 days Visit 16 - eighth and final dose, baseline + 49 days Visit 17 - End of treatment, baseline + 56 days

Inclusion Criteria:

1. Male or female adult ≥ 18 years of age at time of enrollment.

2. Prior confirmed COVID-19 diagnosis by standard reverse transcriptase-polymerase chain reaction (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.
   • 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).

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 Chronic Obstructive Pulmonary Disease (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. New York Heart Association (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