Effectiveness of Treating Post-COVID-19 Conditions (Long COVID) With the SARS-CoV-2 Specific Monoclonal Antibody, Sipavibart
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Patient-Reported Outcomes Measurement Information System-29
研究概览
简要总结
This placebo-controlled, randomized, blinded, two-arm phase II study will test the safety and potential efficacy of the targeted mAb, Sipavibart (formerly AZD3152) in patients with Long COVID.
详细描述
Acute COVID-19 infection can present differently among infected patients, with the infection ranging in symptom presentation from asymptomatic and mild symptomatology to severe illness. Common symptoms tied to a COVID-19 infection include fever, chills, cough, respiratory ailments (shortness of breath or difficulty breathing), fatigue, muscle and/or joint pain, headache, loss of taste or smell, sore throat, congestion, and/or gastrointestinal (GI) disturbances (nausea, vomiting, and/or diarrhea). In some patients, these symptoms are short-lived and span the length of the acute infection, while in many patients the symptoms can linger for an extended period. Early indications point to inflammation playing a key role in acute COVID-19 illness and severity, and may play a role in prolonged Long COVID(LC) symptom intolerance and long-term sequelae. Researchers have demonstrated the involvement of persistent inflammation, poor antiviral responses, and evidence of chronic viral reactivation.
More recently, studies have demonstrated that mAb targeting the spike (S) protein of the SARS-CoV-2 may not only be effective in treating acute COVID-19 infection, especially variants prior to Omicron (alpha, beta, and delta), but also may play a role in addressing Long COVID. This implies that mAb infusions likely target SARS-CoV-2, decreasing activity, and potentially addressing disease pathogenesis tied to its activation, shutting down negative implications of inflammation tied to viral activation. This study will employ a two-arm randomized design to evaluate the efficacy of the drug Sipavibart in individuals experiencing LC symptoms. Participants will undergo six months of follow up after receiving either one dose of Sipavibart or one dose of placebo. After completion of the 6-month follow up, an open-label extension phase will be added at month 6 (week 24), where subjects who continue to experience symptoms of long COVID (regardless of the blinded treatment assignment) could be eligible to receive one dose of Sipavibart in an open-label fashion.
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)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •An individual is eligible for inclusion if all of the following apply:
- •18 to 70 years old,
- •Inciting event: Acute COVID documented by testing (PCR or antigen testing in a clinical setting).
- •Onset of COVID symptoms occurring on or prior to August 31st, 2023; and persistence of symptomatic expression of Long COVID (defined #6 below) for more than 3 months after COVID diagnosis.
- •Current symptomatic expression meets the case definition of ME/CFS.
- •PROMIS 29 score at screening of moderate to severe (≥60).
- •Meets National Academy of Sciences (NAS) criteria for Long COVID with the following provisions:
- •Allowance for normal illnesses of aging, such as hypertension and diabetes, if the conditions are treated and are in demonstrable stable and acceptable ranges at the time of screening and assessment. Specifically, blood pressures < 150 systolic and 90 diastolic mmHg are required.
- •Allowance of stable comorbid conditions common in post viral illness, such as fibromyalgia, irritable bowel, interstitial cystitis, dysautonomia that have not required hospitalization in the two years prior to recruitment.
- •Able to provide written consent to study. Agrees to participate in follow-up visits.
- •Subject Exclusion Criteria
- •An individual is ineligible to participate if any of the following apply:
- •Known active acute SARS-CoV-2 infection ≤ 4 weeks from consent.
- •Known severe anemia, defined as < 8 g/dL.
- •Known stroke that resulted in cognitive impairment within 3 months of enrollment.
- •Self-report of current treated or untreated major depression with psychotic or melancholic features, schizophrenia, bipolar disorder, delusional disorders, dementias of any type, or a history of CNS disorders that may affect cognitive function (i.e., epilepsy, stroke, brain tumor, multiple sclerosis, Parkinson's Disease, Alzheimer's disease), or substance abuse during the last two years, excluding cannabis products.
- •Allergy to any ingredient of the study drug (self-report)
- •Sipavibart is supplied as 150 mg/mL of active ingredient in 20 mM L-histidine/L-histidine hydrochloride, 220 mM L-arginine hydrochloride, and 0.04% (w/v) polysorbate 80, at pH 6.
- •Hypersensitivity to other humanized mAbs.
- •Current heavy alcohol or tobacco use (self-report). Alcohol consumption not to exceed approximately 15 drinks per week (with a drink defined as 12 oz beer, 5 oz wine, or 1.5 oz distilled spirits) and tobacco use not to exceed 20 cigarettes (or equivalent) per day during the last month.
- •Active chronic infections such as HIV, Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV), indicated by self-report, and abnormal liver function tests (>3x upper limit of normal) or evidence in the health record of chronic active hepatitis or human immunodeficiency virus (HIV).
- •Renal disease (self-report; laboratory results: renal insufficiency with serum creatinine > 2.0 mg/dL or eGFR < 44; or currently on renal dialysis)
- •Liver disease (self-report or laboratory results: hepatic insufficiency (bilirubin >2.5mg/dL or transaminases > 3X the upper limits of normal)
- •Uncontrolled diabetes, evidenced by combination of morning blood glucose and previous diagnosis of diabetes, AIC>7
- •Diagnosed with congestive heart failure or significant arrythmia (ventricular tachycardia with a rapid rate at rest (> 100 bpm), persistent atrial fibrillation, or second- or third-degree heart block)
- •Pre-existing sustained severe hypertension (BP >180/110 mmHg in the sitting position)
- •Any of the following within 4 weeks of consent (Self-reported/medical record):
- •an acute myocardial infarction or unstable angina
- •uncontrolled arrhythmias causing symptoms or hemodynamic compromise
- •acute myocarditis or pericarditis, uncontrolled acutely decompensated heart failure (acute pulmonary edema)
- •acute pulmonary embolism
- •suspected dissecting aneurysm
- •severe hypoxemia at rest
- •any acute or chronic disorder that may affect exercise performance, or
- •if they are aggravated by exercise (e.g., infection, thyrotoxicosis, unable to cooperate)
- •Diagnosed bleeding disorders or use of blood-thinning medications.
- •Current or previous receipt of any COVID antiviral medication within 30 days prior to screening (self reported)
- •Currently have exclusionary diagnoses that could reasonably explain the symptoms of their fatiguing illness and their severity, using the exclusion criteria best described in the Ambiguities in case definition paper for CFS, as described in detail in [13] which clarifies exclusionary conditions. These exclusionary diagnoses that are not otherwise listed above comprise:
- •Organ failure
- •Chronic inflammatory diseases
- •Major neurologic diseases that could cause fatigue or neurologic deficits
- •Diseases requiring systemic treatment (i.e., transplantation, chemotherapy, radiation)
- •Major endocrine diseases
- •Untreated primary sleep disorders
- •BMI > 40 kg/m2
- •Temporary conditions discovered at screening, such as
- •Temporary effects of medications
- •Temporary sleep deprivation
- •Untreated hypothyroidism, hypothyroidism that has been inadequately controlled during the last 3 months, or free T4 level not within normal limits
- •Active infection (for COVID-19 infection and other infections, participants may be rescreened six weeks after resolution of infection)
- 另有 8 项未显示
排除标准
- 未提供
研究组 & 干预措施
Sipavibart
Participants receive a single intramuscular dose of Sipavibart, 300 mg intramuscular and are then followed for a duration of six months.
干预措施: Placebo (Drug)
Placebo
Participants receive single dose of placebo (saline) indistinguishable from the active drug in appearance, and are then followed for a duration of six months.
干预措施: Sipavibart (Biological)
结局指标
主要结局
Patient-Reported Outcomes Measurement Information System-29
时间窗: 12 weeks
Comprehensive Symptom Burden Index (CSBI) total scores will serve as a composite outcome measure derived from eight PROMIS domains to capture overall symptom burden. Scores will be calculated at baseline and Week 12. Efficacy will be determined by the proportion of participants classified as IMPROVED, defined as having a ≥4.5-point increase in CSBI from baseline, a threshold representing moderate and clinically meaningful improvement.
Review of Treatment Related Adverse Events
时间窗: 24 weeks
Number of participants with treatment-related adverse events as assessed by frequency of safety events during the study period.
次要结局
- Symptom-specific participant-reported outcome measures(24 weeks)
- Change in Simple Reaction Time (Milliseconds)(Baseline, 12 and 24 weeks)
- Self-reported fatigue using MFI(12 and 24 weeks)
- Change in Heart Rate Post-6MWT(12 and 24 weeks)
- Processing Speed(12 and 24 weeks)
- Attention(Baseline, 12 and 24 weeks)
- Systolic Blood Pressure Response During NASA Lean Test(Baseline, 12 and 24 Weeks)
- Diastolic Blood Pressure Response During NASA Lean Test(Baseline, 12 and 24 Weeks)
- Symptom Score During NASA Lean Test(Baseline, 12 and 24 weeks)
- Within-participant change in PROMIS Fatigue scores from baseline to Week 24(Baseline, 12 weeks, 24 weeks)
- Within-participant change in PROMIS Pain Interference scores(Baseline, 12 weeks, 24 weeks)
- Within-participant change in PROMIS Physical Function scores(Baseline, 12 weeks, 24 weeks)
- Change in PROMIS Cognitive Function 8a T-score(Baseline, 12 Week, 24 week)
- Change in Orthostatic Hypotension Questionnaire (OHQ) composite score(Baseline, 12 weeks, 24 weeks)
- Change in DePaul Symptom Questionnaire-Post-Exertional Malaise (DSQ-PEM)(Baseline, 12 weeks, 24 weeks)
- Change in DePaul Symptom Questionnaire (DSQ) score(Baseline, 12 weeks, 24 weeks)
- Change in Pittsburgh Sleep Quality Index (PSQI) global score(Baseline, 12 weeks, 24 weeks)
- Change in Brief Pain Inventory (BPI) severity score(Baseline, 12 weeks, 24 weeks)
- Change in Modified Medical Research Council (mMRC) Dyspnea Scale score(Baseline, 12 weeks, 24 weeks)
- Change in Generalized Anxiety Disorder-7 (GAD-7) score(Baseline, 12 weeks, 24 weeks)
- Change in Patient Health Questionnaire-8 (PHQ-8) score(Baseline, 12 weeks, 24 weeks)
- Change in Brief Illness Perception Questionnaire (B-IPQ) total score(Baseline, 12 weeks, 24 weeks)
- Change in Functional Capacity Scale (FUNCAP) score(Baseline, 12 weeks, 24 weeks.)
- Change in Composite Symptom Burden Index (CSBI) score(Baseline, 12 weeks, 24 weeks)
研究者
Nancy Klimas
Director, Institute for Neuro Immune Medicine
Nova Southeastern University