Study to Evaluate the Efficacy and Safety of Ampligen in Patients With Post-COVID Conditions

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of Ampligen® administered twice weekly by intravenous (IV) infusions in subjects experiencing the Post-COVID Condition of fatigue.

Detailed Description
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This is a Phase 2, two-arm, randomized, double blind, placebo controlled multicenter study to evaluate the efficacy and safety of Ampligen® in patients experiencing the Post-COVID Condition of fatigue. Patients will be randomized 1:1 to receive twice weekly IV infusions of Ampligen® or placebo.

Official Title
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A Randomized, Double Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Ampligen® in Patients With Post-COVID Conditions

Conditions
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Post COVID-19 Condition, Long COVID

Intervention / Treatment
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* Drug: Rintatolimod
* Other: Placebo / Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female adult between 18 to 60 (inclusive) years of age at time of enrollment. Prior confirmed COVID-19 diagnosis by standard RT-PCR assay or equivalent testing at least 12 weeks prior to baseline. Note: For subjects with COVID-19 symptoms who were not tested for the presence of SARS-CoV-2, a positive serum antibody test for SARS-CoV-2 will be sufficient in subjects not vaccinated for COVID-19 or it can be shown that the positive antibody cannot be associated with the COVID-19 vaccination. Laboratory confirmed negative SARS-CoV-2 (COVID-19) infection by a government approved test / kit at time of enrollment. Subject meets the criteria of fatigue per the 1994 CDC Case Definition for Chronic Fatigue Syndrome (CFS): Unexplained persistent or relapsing chronic fatigue that is of new or definite onset (i.e., not lifelong), is not the result of ongoing exertion, is not substantially alleviated by rest, and results in substantial reduction in previous levels of occupational, educational, social, or personal activities. The fatigue must have persisted or recurred during 3 or more consecutive months of illness and must not have preceded the onset of the COVID-19 symptoms. PROMIS® Fatigue- Short Form 7a score of ≥21 at screening and baseline. Electrocardiogram (ECG) with no clinically significant findings as assessed by the Investigator. Note: Below are the examples of clinically significant ECG abnormalities: Previous documented evidence of myocardial infarction or recent significant change in the resting EKG suggesting infarction or other acute cardiac events. Current symptoms of coronary insufficiency (i.e. - angina pectoris and/or ST segment depression on EKG). Evidence of uncontrolled atrial or frequent or complex ventricular ectopy, or myocardial conduction defect which would increase the risk of syncope (for example, second degree or higher A-V block). Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures. 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). 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. Subject is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures and study restrictions. Exclusion Criteria: Inability to provide informed consent or to return to the Investigator's site for scheduled infusions and evaluations. Exhibiting signs of moderate or severe pulmonary disease (such as COPD, asthma, or pulmonary fibrosis). Ongoing requirement of oxygen therapy. Pulse oxygen saturation (SpO2) of <94% on room air at the time of screening. Thrombocytopenia (platelets <100×109/L), anemia (hemoglobin <9.0 g/dL), or leukopenia (WBC <3×109/L) on screening labs History of splenectomy. Known hypercoagulable state or at increased risk of thrombosis (e.g., due to immobility) Liver cirrhosis or patient showing signs of clinical jaundice at the time of screening. Transaminase (ALT or AST) >3X ULN or total bilirubin >2X ULN at screening Chronic kidney disease stage 4 or requiring dialysis at the time of screening. Estimated GFR <60 mL/min/1.73 m2 at the time of screening NYHA Class III or IV congestive heart failure (CHF). Exhibiting signs of uncontrolled hypo-or hyper-thyroidism at the time of Screening. Diagnosis of autoimmune disease (e.g., SLE, rheumatoid arthritis, psoriasis) at the time of screening Uncontrolled rheumatologic disorders at the time of screening. Diagnosis of sleep apnea (central or obstructive) 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 psychotic or melancholic features, bipolar disorders, schizophrenia of any subtype, schizoaffective disorder, major depression delusional disorders of any subtype, dementias of any subtype, anorexia nervosa or bulimia nervosa. 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, chronic or intercurrent active medical disorder and other reasons which would interfere with study conduct or study results interpretation per the Investigator. Chronic or intercurrent acute medical disorder or disease making implementation or interpretation of the protocol or results difficult or unsafe per the investigator. Therapy with interferons, interleukins, or other cytokines or investigational drugs within 6 weeks of beginning study medication. Subjects must give written informed consent prior to discontinuation of investigational drugs. Treatment with any of the following therapies within the eight (8) weeks immediately preceding the start of study baseline or during baseline: systemic glucocorticoids (i.e., hydrocortisone, prednisone, etc.) or mineralocorticoids (i.e., fludrocortisone (Florinef), etc.), interferons, interleukin-2, systemic antivirals, gamma globulin or investigational drugs or experimental agents not yet approved for use in the United States. Prior participation in an Ampligen® study. Medical necessity, as determined by the patient's primary doctor or the principal investigator, to continue aspirin (ASA) or non-steroidal anti-inflammatory (NSAID) drugs for 20 consecutive days or for more than 10% of the study duration. History of congestive heart failure, suspected or known dissecting aneurysm, recent systemic or pulmonary embolus or myocardial infarction (≤ 6 months), severe valvular heart disease, ventricular aneurysm, active or suspected myocarditis or pericarditis, thrombophlebitis or intracardiac thrombi, or acute infection. Evidence of moderate or severe obstructive pulmonary disease. Resting diastolic blood pressure > 115 mm Hg or resting systolic blood pressure > 200 mm Hg. Uncontrolled metabolic disease (e.g., diabetes, thyrotoxicosis, or myxedema). Concurrent use of any beta blockers and/or bronchodilators which cannot remain at a stable dosage level during baseline and the study. History of alcohol or other substance abuse within two (2) years before the onset of acute COVID-19 or at any time afterward. History of suicidal ideation, suicide attempt, or suicidal behavior within two (2) years of baseline. A score of 10 or greater on the PHQ-9 at Baseline indicates symptoms of depression and will exclude subject. A score of greater than zero on question nine (9) of the PHQ-9 at Baseline indicates suicidal ideation and will exclude subject. Pregnant or breast feeding. Participation in another study for an investigational treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ampligen / rintatolimod<br>Subjects will receive rintatolimod (intravenous [IV]), up to 400 mg twice weekly for 12 weeks. | Drug: Rintatolimod<br>* 100 to 400 mg twice weekly<br>* Other names: Rintatolimod (poly I : poly C12U);|
| Placebo Comparator: Placebo / Saline<br>Subjects will receive placebo / normal saline (intravenous [IV]), up to 160 mL twice weekly for 12 weeks. | Other: Placebo / Normal Saline<br>* 40 to 160 mL twice weekly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PROMIS® Fatigue Score (T-Score) | Change from baseline to week 13 in PROMIS® Fatigue Score (T-Score) | Baseline to Week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PROMIS® Fatigue Score (T-Score) | Change from baseline to week 6 in PROMIS® Fatigue Score (T-Score) | Baseline to Week 6 | 
| 6-minute walk test | Change from baseline to week 6 and 13 in distance traveled during a 6-minute walk test | Baseline to Week 6 and 13 | 
| 6-minute walk test | Proportion of subjects with minimal clinically important difference (MCID), defined as at least 54 m, in the Six-Minute Walk Test (6MWT) at the end of 12-week treatment phase. | End of 12 week treatment phase | 
| PROMIS® Cognitive Function Score (T-Score) | Change from baseline to week 6 and 13 in PROMIS® Cognitive Function Score (T-Score) | Baseline to Week 6 and 13 | 
| PROMIS® Sleep Disturbance Score (T-Score) | Change from baseline to week 6 and 13 in PROMIS® Sleep Disturbance Score (T-Score) | Baseline to Week 6 and 13 |