A Double-blind, Randomized Study to Evaluate the Efficacy and Safety of Bezisterim (NE3107) in Adults With Long COVID
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- BioVie Inc.
- 入组人数
- 203
- 试验地点
- 30
- 主要终点
- Change from Baseline in performance on the Cogstate Cognition battery*
研究概览
简要总结
Long COVID is a condition where debilitating symptoms can persist for months after a COVID-19 infection. This study aims to evaluate the effects of NE3107 on several neurological symptoms reported in people with Long COVID including difficulty concentrating or remembering things ("brain fog") and fatigue.
This study is designed as a signal-seeking proof-of-concept Phase 2 study. The primary outcome is intended for estimation and hypothesis generation rather than formal hypothesis testing. No single endpoint is designated as definitive for study success.
Researchers will compare NE3107 to a placebo (a look-alike substance that contains no drug) to see if NE3107 works to treat neurocognitive and fatigue symptoms of long COVID.
Participants will:
- Take NE3107 or a placebo twice daily for 84 days
- Visit the clinic 5 times for checkups and tests and have a follow up phone call
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
The participant, investigator, assessors, or any member of the study staff at the CRO or sponsor will be masked to the treatment assignments.
入排标准
- 年龄范围
- 18 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult participants ≥18 to <70 years of age at Screening
- •Long COVID with neurological symptoms as defined below:
- •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-
- •Note that a documented diagnosis of Long COVID is not required for inclusion.
- •Symptoms cannot be explained by any concomitant condition or diagnosis, in the opinion of the investigator.
- •Symptom duration for at least 3 months.
- •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.
- •PROMIS Fatigue SF13a T score ≥ 50 (≥ normative mean) after rounding to nearest integer.
- •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.
- •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).
- •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)
- •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
- •Must meet one of the following criteria:
- •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.
- •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.
- •Willing to allow collection of blood for DNA methylation analysis.
- •Participant has native-level proficiency in English.
排除标准
- •Positive SARS-CoV-2 nucleic acid or rapid Antigen test in the past 28 days
- •Received a vaccination for COVID-19 or influenza within 2 weeks of randomization
- •Previous admission to the intensive care unit for COVID-19-related symptoms and/ or if intubated (i.e. mechanical ventilation) for COVID-19 care.
- •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:
- •Progressive neurodegenerative disease, such as Alzheimer's disease, Parkinson's disease, etc.
- •Past traumatic brain injury occurrence still associated with active post-concussive symptoms
- •History of epilepsy or seizure disorder requiring ongoing treatment, or any seizure or loss of consciousness within 12 months prior to Screening
- •Post-stroke deficits that may interfere with assessment, such as language or communication difficulties, aphasia, etc.
- •Formal thought disorders, such as schizophrenia, psychotic bipolar disorder etc.
- •Any neuropsychiatric or neurologic disorder uncontrolled for the previous six months or that may interfere with assessment, at discretion of the investigator
- •Functional neurologic disorder
- •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 ≥
- •(If the PHQ-2 score is ≥3 the investigator should discuss with the BioVie Medical Monitor to confirm eligibility)
- •Premenstrual dysphoric disorder (PMDD)
- •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.
- •Diagnosed reading disability or dyslexia, or clinically significant learning disorder by history.
- •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.
- •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.
- •Diagnosis of narcolepsy.
- •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.
- •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.
- •Electrocardiogram with 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 ECG suggesting infarction or other acute cardiac events.
- •Current symptoms of coronary insufficiency (i.e. angina pectoris and/or ST segment depression on ECG).
- •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).
- •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].
- •History of moderate or severe chronic obstructive pulmonary disease or moderate or severe asthma.
- •History of chronic fatigue syndrome, fibromyalgia, or postural orthostatic tachycardia syndrome (POTS) prior to index COVID-19 infection
- •Known diagnosis of chronic Lyme disease or tertiary syphilis with persistent symptoms, sequelae, or related therapy.
- •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.
- •Screening lab abnormalities that may indicate alternate explanation for fatigue or cognitive impairment, such as severe anemia, hypocalcemia, or thyroid dysfunction.
- •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)
- •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.
- •Hemoglobin ≤ 10 g/dL if female, ≤11.5 g/dL if male
- •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.
- •Creatinine clearance (CKD-EPI Creatinine Equation 202139 of <45 mL/min).
- •Untreated diabetes with hemoglobin A1c > 9.
- •Pregnant or lactating.
- •History of:
- •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
- •Current unstable medical illness which would interfere with interpretation of the data.
- •Recent thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, etc.) within 6 months prior to randomization.
- •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-
- •Suicidality risk:
- •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;
- •History of a suicide attempt in the previous 2 years or;
- •Participant is at serious suicide risk in the investigator's clinical judgment.
- •Lifetime history of breast cancer.
- •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.
- •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.
- 另有 10 项未显示
研究组 & 干预措施
Placebo
One 20 mg capsule containing placebo taken by mouth twice daily (BID)
干预措施: Placebo (Drug)
NE3107
One 20 mg capsule containing NE3107 taken by mouth twice daily (BID)
干预措施: NE3107 (Drug)
结局指标
主要结局
Change from Baseline in performance on the Cogstate Cognition battery*
时间窗: 12 Weeks
\*This study is designed as a signal-seeking proof-of-concept Phase 2 study. The primary outcome is intended for estimation and hypothesis generation rather than formal hypothesis testing. No single endpoint is designated as definitive for study success. Objective computerized neurocognitive testing using Cogstate battery assessing attention, sustained attention, verbal memory, verbal learning, psychomotor function and processing speed. A composite cognitive score is calculated as the mean of standardized (z-score-transformed) performance scores across the tasks. Higher composite scores indicate better cognitive performance.
Change from Baseline in PROMIS Cognitive Function Short Form 8a (SF-8a)
时间窗: 12 Weeks
Patient-reported assessment of perceived cognitive abilities, including memory, attention, and mental acuity. Scores are standardized T-scores, T-scores are a continuous variable. The mean in the general population is 50 (SD=10). Scores below 50 represent worse cognitive function.
Change from Baseline in PROMIS Fatigue Short Form 13a (SF-13a)
时间窗: 12 Weeks
The PROMIS Fatigue SF-13a assesses patient-reported fatigue severity and impact over the prior 7 days. Scores are standardized T-scores, T-scores are a continuous variable. The mean in the general population is 50 (SD=10). Scores above 50 represent worse fatigue severity
Change from Baseline in PROMIS Sleep Disturbance Short Form 8a (SF-8a)
时间窗: 12 Weeks
Patient-reported measure of sleep quality, depth, and restoration. Scores are standardized T scores and T scores are a continuous variable. The mean in the general population 50 (SD=10), with higher scores reflecting greater sleep disturbance.
Change from Baseline in SF-12 Health Survey (Physical Component Scores)
时间窗: 12 Weeks
Generic quality-of-life assessment evaluating physical (PCS) and mental (MCS) health domains which are normalized to a mean of 50 (SD=10) with scores lower scores indicating worse physical function
Change from Baseline in SF-12 Health Survey (Mental Component Scores)
时间窗: 12 Weeks
Generic quality-of-life assessment evaluating physical (PCS) and mental (MCS) health domains which are normalized to a mean of 50 (SD=10) with lower scores indicating worse mental health
Change from Baseline in DePaul Symptom Questionnaire (DSQ) Post-Exertional Malaise
时间窗: 12 Weeks
DSQ-PEM evaluates the presence or absence of PEM and myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) and the severity and frequency of PEM symptoms. Participants rate both frequency and severity of PEM symptoms. Frequency is rated on a 5-point Likert scale (0 = none of the time, 1 = a little of the time, 2 = about half the time, 3 = most of the time, 4 = all of the time). Severity is rated on a 5-point Likert scale (0 = symptom not present, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe). Post-exertional malaise is considered present if the participant reports at least one PEM symptom with a severity score ≥2 (moderate or greater) and a frequency score ≥2 (about half the time or more). The outcome measure is the change from baseline in the exercise intolerance symptom cluster score derived from the DSQ-PEM.
Composite Benefit Score
时间窗: 12 Weeks
Composite Benefit Score (CBS), Composite endpoint consisting of clinically relevant symptom measures. Lower scores indicate improvement in Long COVID symptoms.
Change from Baseline in performance on the Cogstate Cognition battery
时间窗: 12 Weeks
Objective computerized neurocognitive testing assessing attention, sustained attention, verbal memory, verbal learning, psychomotor function and processing speed. A composite cognitive score is calculated as the mean of standardized (z-score-transformed) performance scores across the tasks. Higher composite scores indicate better cognitive performance.
次要结局
- Exploratory biomarkers(12 Weeks)
- Change from Baseline in PROMIS Cognitive Function Short Form 8a (SF-8a)(12 Weeks)
- Change from Baseline in PROMIS Fatigue Short Form 13a (SF-13a)(12 Weeks)
- Change from Baseline in PROMIS Sleep Disturbance Short Form 8a (SF-8a)(12 Weeks)
- Change from Baseline in SF-12 Health Survey (Physical and Mental Component Scores)(12 Weeks)
- Change from Baseline in DePaul Symptom Questionnaire (DSQ) Post-Exertional Malaise (PEM(12 Weeks)