Saves the questions and what to expect into your notes, next to the visit they belong to.
Keep this study
Lead
BioVie Inc.
Age
18–69
Sex
ALL
Healthy volunteers
Not accepted
You may be eligible if
1. Adult participants ≥18 to \<70 years of age at Screening
2. Long COVID with neurological symptoms as defined below:
1. Current symptoms of at least fatigue and neurocognitive impairment that began or worsened after an index SARS-CoV-2 infection that occurred at least 3 months prior to screening. Index SARS-CoV-2 infection is defined as either: 1) an episode of COVID-19 with a positive nucleic acid or antigen test during acute illness, as documented in the medical record, or 2) a documented clinical diagnosis of COVID-19, which can be based on a patient-reported positive test for COVID-19. Note that a documented diagnosis of Long COVID is not required for inclusion.
2. Symptoms cannot be explained by any concomitant condition or diagnosis, in the opinion of the investigator.
3. Symptom duration for at least 3 months.
3. PROMIS Cognitive Function SF8a T score ≤ 40 (≥ 1 SD below normative mean) after rounding to nearest integer. If the T score is marginally exclusionary, a subject may be allowed following discussion between the investigator and BioVie Medical Monitor.
4. PROMIS Fatigue SF13a T score ≥ 50 (≥ normative mean) after rounding to nearest integer.
5. If taking medications for glycemic control at the time of Screening, must be stable on the current dosage and form for ≥ 3 months prior to randomization and expected to remain stable throughout participation in the study.
6. Willing and able to provide voluntary written informed consent, complete the surveys, clinical assessments, and participate in the virtual follow-up visit at the end of the 4-week follow-up period (the End of Study visit).
7. Agree to maintain any other regular medications at current doses for the duration of the trial (except for essential need of new medication or dose change, as prescribed by a physician)
8. Females taking hormone replacement therapy (HRT) must have maintained a stable regimen for at least 6 months prior to randomization and agree to continue the regimen until completing the final safety assessment in Week 16.
9. Must meet one of the following criteria:
1. Females: Must be postmenopausal (postmenopausal status must be confirmed as no menstrual bleeding for \>1 year, or via a follicle stimulating hormone \[FSH\] assessment at Screening), or have been surgically sterilized (e.g., hysterectomy, bilateral oophorectomy, or tubal ligation) at least 6 months prior to Screening or agree to highly effective contraception, such as double barrier methods (e.g. condom with spermicide, IUD with spermicide). Oral contraceptives alone are insufficient.
2. Males: If not vasectomized, must be abstinent or agree to use a double barrier contraception method and indicate that their partner is using highly effective birth control (as defined in 11a) until the end of the study.
10. Willing to allow collection of blood for DNA methylation analysis.
11. Participant has native-level proficiency in English.
You may not be if
1. Positive SARS-CoV-2 nucleic acid or rapid Antigen test in the past 28 days
2. Received a vaccination for COVID-19 or influenza within 2 weeks of randomization
3. Previous admission to the intensive care unit for COVID-19-related symptoms and/ or if intubated (i.e. mechanical ventilation) for COVID-19 care.
4. Prior or active unstable or progressive major psychiatric or neurologic condition that may impact ability to determine a treatment effect and is not related to SARS-CoV-2 infection, including, but not limited to, the following examples as determined by the investigator:
1. Progressive neurodegenerative disease, such as Alzheimer's disease, Parkinson's disease, etc.
2. Past traumatic brain injury occurrence still associated with active post-concussive symptoms
3. History of epilepsy or seizure disorder requiring ongoing treatment, or any seizure or loss of consciousness within 12 months prior to Screening
4. Post-stroke deficits that may interfere with assessment, such as language or communication difficulties, aphasia, etc.
5. Formal thought disorders, such as schizophrenia, psychotic bipolar disorder etc.
6. Any neuropsychiatric or neurologic disorder uncontrolled for the previous six months or that may interfere with assessment, at discretion of the investigator
7. Functional neurologic disorder
8. Major Depressive Disorder not on stable treatment for at least 3 months prior to Screening and not planning to stay on a stable dose through the study, or a PHQ-2 score ≥ 3. (If the PHQ-2 score is ≥3 the investigator should discuss with the BioVie Medical Monitor to confirm eligibility)
9. Premenstrual dysphoric disorder (PMDD)
5. In the opinion of the investigator any physical, cognitive (for example intellectual disability or pre-dementia), or language impairments sufficient to adversely affect data derived from cognitive assessments.
6. Diagnosed reading disability or dyslexia, or clinically significant learning disorder by history.
7. Documented attention deficit hyperactivity disorder (ADHD) being treated with psychostimulants. Individuals diagnosed with ADHD being treated with non-stimulants must be stable on the current dosage for ≥ 3 months prior to randomization and expected to remain stable throughout participation in the study.
8. Known active bacterial, fungal, viral, or other infection besides SARS-CoV-2 requiring treatment within 28 days prior to randomization and meeting criteria for systemic involvement upon review by the site investigator. Note: Mild or limited infections such as uncomplicated urinary tract or yeast infections, sexually transmitted infections, and mild dermatophyte infections may be reviewed with the study investigator but are not exclusionary.
9. Diagnosis of narcolepsy.
10. History of obstructive sleep apnea unless the participant is compliant with prescribed treatment (e.g., CPAP or BiPAP therapy) as confirmed by medical records or clinician assessment.
11. 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.
12. Electrocardiogram with clinically significant findings as assessed by the Investigator. Note: Below are the examples of clinically significant ECG abnormalities:
1. Previous documented evidence of myocardial infarction or recent significant change in the resting ECG suggesting infarction or other acute cardiac events.
2. Current symptoms of coronary insufficiency (i.e. angina pectoris and/or ST segment depression on ECG).
3. 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).
4. QT prolongation (QTcF \>450 msec (male) or \>470 msec (female) \[If QTcF is marginally above these values, a subject may still be allowed on a case-by-case basis following discussion between the investigator and medical monitor\].
13. History of moderate or severe chronic obstructive pulmonary disease or moderate or severe asthma.
14. History of chronic fatigue syndrome, fibromyalgia, or postural orthostatic tachycardia syndrome (POTS) prior to index COVID-19 infection
15. Known diagnosis of chronic Lyme disease or tertiary syphilis with persistent symptoms, sequelae, or related therapy.
16. History of human immunodeficiency virus (1 and 2), chronic hepatitis B, or hepatitis C. Participants with hepatitis C who had spontaneous resolution or received successful curative treatment (e.g., HARVONI® \[ledipasvir/sofosbuvir\]) with documentation of undetectable viral load for at least 3 months may be allowed.
17. Screening lab abnormalities that may indicate alternate explanation for fatigue or cognitive impairment, such as severe anemia, hypocalcemia, or thyroid dysfunction.
18. Has any of the following laboratory findings at Screening (marginally exclusionary lab values that appear to be artifactual or likely, in the investigator's opinion, to represent a transient and benign condition may still be allowed)
1. Alanine aminotransferase (ALT) \> 2 × upper limit of normal (ULN), aspartate aminotransferase (AST) \> 2 × ULN, or history of clinically significant liver disease, in the investigator's medical judgment.
2. Hemoglobin ≤ 10 g/dL if female, ≤11.5 g/dL if male
3. International normalized ratio (INR) \> 1.5 if not on anticoagulant medication; if the participant is on anticoagulant medication, the anticoagulant medication should be optimized and on a stable dose for ≥ 4 weeks prior to Screening.
4. Creatinine clearance (CKD-EPI Creatinine Equation 202139 of \<45 mL/min).
5. Untreated diabetes with hemoglobin A1c \> 9.0.
19. Pregnant or lactating.
20. History of:
1. Cancer requiring systemic therapy within the last 5 years, except for localized basal cell carcinoma of the skin or in-situ cervical cancer successfully treated with surgical excision or
2. Current unstable medical illness which would interfere with interpretation of the data.
3. Recent thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, etc.) within 6 months prior to randomization.
21. History of alcohol use disorder or substance use disorder within 12 months of Screening as defined by the Diagnostic and Statistical Manual of Mental Disorders-5.
22. Suicidality risk:
1. Per C-SSRS: History of active suicidal thoughts (answers 'Yes' on questions 4 or 5 on the C-SSRS) in the 6 months prior to Screening or;
2. History of a suicide attempt in the previous 2 years or;
3. Participant is at serious suicide risk in the investigator's clinical judgment.
23. Lifetime history of breast cancer.
24. Participant is unwilling to not begin, resume, or increase the dose of any form of cognitive training or cognitive-enhancing supplements until the end of the active intervention phase of the trial. Cognitive training is any non-pharmacological intervention that participants started intending to enhance their cognition. A cognitive-enhancing supplement is any non-prescription compound being taken by participants with the goal of enhancing their cognition.
25. Participant is unwilling to refrain from the use of prohibited medications for the duration of the study and the use of restricted medications within 12 hours prior to assessments.
26. Autoimmune diseases are exclusionary only if the participant is receiving or likely to require initiation of immunomodulatory treatment that would confound the interpretation of the study data during the participant's participation in this study.
27. Requirement for supplemental oxygen at the time of screening, unless the participant has been on a stable supplemental oxygen regimen for at least 3 months prior to screening.
28. Received investigational agents as part of a separate study within 30 days prior to the screening visit or 90 days for biologics, prior to the screening visit.
29. Received a direct-acting antiviral agent for COVID infection within the past 2 weeks, or tumor necrosis factor (TNF) inhibitors within the past 90 days prior to the screening visit.
30. Received systemic or intraarticular steroids within 28 days prior to randomization. An oral corticosteroid regimen of no more than 7 days is allowed within 28 days prior to randomization. Allowable regimens can be a tapered regimen or, if a tapered regimen is not required, a regimen where single daily doses do not exceed 20 mg/day.
31. Any medical intervention, including surgery planned to occur during the study, that, in the investigator's opinion, would impede or confound study assessments.
32. Participants who are relatives of the sponsor or sponsor representatives are to be excluded from screening and participation. Relatives of study site personnel may not participate at the site where a relative is employed or otherwise affiliated with the site.
33. Participants taking naltrexone at a dose \> 4.5mg/day. Participants on a dose of ≤ 4.5 mg/day must be stable on the current dosage for ≥ 3 months prior to randomization and expected to remain stable throughout participation in the study.
34. Use of or requirement for potent CYP3A4 inhibitors-including clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, or verapamil, within 14 days of randomization or within 5 half-lives of the drug, whichever is shorter.
35. Confirmed positive urine drug screen for amphetamine, barbiturates, cocaine and metabolites, methadone, methamphetamines, MDMA, opiates, oxycodone or phencyclidine. Note -THC and benzodiazepines are not exclusionary but have restrictions
