Clinical trial NCT05592418: Study to Evaluate the Efficacy and Safety of Ampligen in Patients With Post-COVID Conditions
Official title: A Randomized, Double Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Ampligen® in Patients With Post-COVID Conditions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Post COVID-19 Condition
Long COVID
Lead sponsor: AIM ImmunoTech Inc.
Sponsor class: INDUSTRY
Collaborators: name: Amarex Clinical Research
First posted: 2022-10-24
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Male or female adult between 18 to 60 (inclusive) years of age at time of enrollment.
2. 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.
3. Laboratory confirmed negative SARS-CoV-2 (COVID-19) infection by a government approved test / kit at time of enrollment.
4. 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.
5. PROMIS® Fatigue- Short Form 7a score of ≥21 at screening and baseline.
6. 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).
7. Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
8. 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).
9. 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.
10. Subject is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures and study restrictions.

Exclusion Criteria:

1. Inability to provide informed consent or to return to the Investigator's site for scheduled infusions and evaluations.
2. Exhibiting signs of moderate or severe pulmonary disease (such as COPD, asthma, or pulmonary fibrosis).
3. Ongoing requirement of oxygen therapy.
4. Pulse oxygen saturation (SpO2) of \<94% on room air at the time of screening.
5. Thrombocytopenia (platelets \<100×109/L), anemia (hemoglobin \<9.0 g/dL), or leukopenia (WBC \<3×109/L) on screening labs
6. History of splenectomy.
7. Known hypercoagulable state or at increased risk of thrombosis (e.g., due to immobility)
8. Liver cirrhosis or patient showing signs of clinical jaundice at the time of screening.
9. Transaminase (ALT or AST) \>3X ULN or total bilirubin \>2X ULN at screening
10. Chronic kidney disease stage 4 or requiring dialysis at the time of screening.
11. Estimated GFR \<60 mL/min/1.73 m2 at the time of screening
12. NYHA Class III or IV congestive heart failure (CHF).
13. Exhibiting signs of uncontrolled hypo-or hyper-thyroidism at the time of Screening.
14. Diagnosis of autoimmune disease (e.g., SLE, rheumatoid arthritis, psoriasis) at the time of screening
15. Uncontrolled rheumatologic disorders at the time of screening.
16. Diagnosis of sleep apnea (central or obstructive) at the time of screening.
17. History of organ transplantation or are candidates for organ transplantation at the time of screening.
18. History of Chronic Fatigue Syndrome prior to COVID-19 infection.
19. History of fibromyalgia prior to COVID-19 infection.
20. 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.
21. Any malignancy within the past 5 years, excluding successfully treated basal cell carcinoma or squamous cell carcinoma without evidence of metastases.
22. 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.
23. Chronic or intercurrent acute medical disorder or disease making implementation or interpretation of the protocol or results difficult or unsafe per the investigator.
24. 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.
25. 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.
26. Prior participation in an Ampligen® study.
27. 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.
28. 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.
29. Evidence of moderate or severe obstructive pulmonary disease.
30. Resting diastolic blood pressure \> 115 mm Hg or resting systolic blood pressure \> 200 mm Hg.
31. Uncontrolled metabolic disease (e.g., diabetes, thyrotoxicosis, or myxedema).
32. Concurrent use of any beta blockers and/or bronchodilators which cannot remain at a stable dosage level during baseline and the study.
33. History of alcohol or other substance abuse within two (2) years before the onset of acute COVID-19 or at any time afterward.
34. 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.
35. Pregnant or breast feeding.
36. Participation in another study for an investigational treatment.

Primary outcomes:
measure: Change From Baseline to Week 13 in PROMIS Fatigue Score (T-Score)
timeFrame: Baseline and Week 13
Secondary outcomes:
measure: Change From Baseline to Week 6 in PROMIS Fatigue Score (T-Score)
timeFrame: Baseline to Week 6
measure: Change From Baseline to Week 13 in PROMIS Fatigue Score (T-Score), Excluding Response to Item Seven
timeFrame: Baseline to Week 6 and 13
measure: Change From Baseline to Week 6 and Week 13 in Distance Traveled During 6-minute Walk Test (6MWT)
timeFrame: Baseline to week 6 and week 13
measure: Percentage of Subjects With Minimal Clinically Important Difference (MCID)
timeFrame: End of 12 week treatment phase
measure: Change From Baseline to Week 6 and 13 in PROMIS Cognitive Function Converted Score (T-Score).
timeFrame: Baseline to Week 6 and 13
measure: Change From Baseline to Week 6 and 13 in PROMIS Sleep Disturbance Score (T-Score)
timeFrame: Baseline to Week 6 and 13
Other outcomes:
measure: Changes From Baseline in COVID-19-related Symptoms Using Symptom Burden Questionnaire for Long COVID (SBQ-LC) During the Course of the Treatment Phase.
timeFrame: Baseline and the end of treatment phase at week 12
measure: Change From Baseline in Cognitive Function as Measured by Montreal Cognitive Assessment (MoCA) at Weeks 4, 8, and 13 During the Treatment Phase
timeFrame: Baseline to weeks 4, 8 and 13 during treatment phase
measure: Hospitalizations
timeFrame: During the treatment phase up to 12 weeks
measure: Duration of Hospitalizations
timeFrame: During the treatment phase up to 12 weeks
measure: Evaluation of Lymphocyte Profile by Flow Cytometry in Patients With Post-COVID-19 Conditions - Absolute Value of CD3+
timeFrame: Baseline to week 6 and 13
measure: Evaluation of Lymphocyte Profile by Flow Cytometry in Patients With Post-COVID-19 Conditions - Absolute Value of CD3-CD56+ Natural Kill
timeFrame: Baseline to week 6 and 13
measure: Evaluation of Lymphocyte Profile by Flow Cytometry in Patients With Post-COVID-19 Conditions - CD4:CD8 Ratio
timeFrame: Baseline to week 6 and 13
measure: Identification and Evaluation of Plasma Protein Biomarkers in Patients With Post-COVID-19 Conditions
timeFrame: Baseline and week 13
Locations:
city: Canoga Park
country: United States
facility: Hope Clinical Research
state: California
city: Inglewood
country: United States
facility: 310 Clinical Research
state: California
city: San Diego
country: United States
facility: Acclaim Clinical Research
state: California
city: Davie
country: United States
facility: Alfa Medical Research
state: Florida
city: Dallas
country: United States
facility: Zenos Clinical Research
state: Texas
Study officials:
affiliation: AIM ImmunoTech Inc.
name: David R Strayer, MD
role: STUDY_DIRECTOR
References: