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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
100
A single dose of placebo (saline) indistinguishable from the active drug in appearance
A single intramuscular dose of Sipavibart, 300 mg
Nova Southeastern University
Fort Lauderdale, Florida, United States
RECRUITINGPatient-Reported Outcomes Measurement Information System-29
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.
Time frame: 12 weeks
Review of Treatment Related Adverse Events
Number of participants with treatment-related adverse events as assessed by frequency of safety events during the study period.
Time frame: 24 weeks
Symptom-specific participant-reported outcome measures
Evaluate change in Comprehensive Symptom Burden Index (CSBI) score from baseline to Week 24 between Sipavibart and placebo groups.
Time frame: 24 weeks
Change in Simple Reaction Time (Milliseconds)
Change in raw Simple Reaction Time, measured in milliseconds using the CNS Vital Signs computerized test battery, from baseline to Weeks 12 and 24.
Time frame: Baseline, 12 and 24 weeks
Self-reported fatigue using MFI
Change in Multidimensional Fatigue Inventory (MFI) total and subscale scores (General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Activity, Reduced Motivation) from baseline to Weeks 12 and 24. Correlation of MFI scores with PROMIS Fatigue and DSQ-PEM subscales (convergent validity).
Time frame: 12 and 24 weeks
Change in Heart Rate Post-6MWT
Change in Heart Rate post 6-minute walk distance (6MWT), in meters, from baseline to Weeks 12 and 24.Unit: Beats per minute (bpm)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: 12 and 24 weeks
Processing Speed
Change in Processing Speed score (Standard score or percentile) from baseline to Weeks 12 and 24 as measured by CNS Vital Signs.
Time frame: 12 and 24 weeks
Attention
Change in Attention (Standard Score) from baseline to Weeks 12 and 24 as measured by CNS Vital Signs.
Time frame: Baseline, 12 and 24 weeks
Systolic Blood Pressure Response During NASA Lean Test
Change in systolic blood pressure (mmHg) from baseline to 10 minutes upright during the NASA Lean Test
Time frame: Baseline, 12 and 24 Weeks
Diastolic Blood Pressure Response During NASA Lean Test
Change in diastolic blood pressure (mmHg) from baseline to 10 minutes upright during the NASA Lean Test
Time frame: Baseline, 12 and 24 Weeks
Symptom Score During NASA Lean Test
Change in self-reported orthostatic intolerance symptom score, measured using a 0-10 numeric scale, during the NASA 10-minute Lean Test
Time frame: Baseline, 12 and 24 weeks
Within-participant change in PROMIS Fatigue scores from baseline to Week 24
PROMIS Fatigue domain score measured at baseline, Week 12, and Week 24 to assess change over time.
Time frame: Baseline, 12 weeks, 24 weeks
Within-participant change in PROMIS Pain Interference scores
PROMIS Pain Interference domain score measured at baseline, Week 12, and Week 24 to assess change over time.
Time frame: Baseline, 12 weeks, 24 weeks
Within-participant change in PROMIS Physical Function scores
PROMIS Physical Function domain score measured at baseline, Week 12, and Week 24 to assess change over time.
Time frame: Baseline, 12 weeks, 24 weeks
Change in PROMIS Cognitive Function 8a T-score
Evaluates cognitive function using PROMIS Cognitive Function 8a at baseline, Week 12, and Week 24. Used to assess differential treatment effects by baseline symptom cluster (Cognitive Dysfunction group).
Time frame: Baseline, 12 Week, 24 week
Change in Orthostatic Hypotension Questionnaire (OHQ) composite score
Evaluates autonomic dysfunction using the OHQ at baseline, Week 12, and Week 24. Used to assess differential treatment effects by baseline symptom cluster (Autonomic Dysfunction group).
Time frame: Baseline, 12 weeks, 24 weeks
Change in DePaul Symptom Questionnaire-Post-Exertional Malaise (DSQ-PEM)
Evaluates post-exertional malaise and exercise intolerance using the DSQ-PEM T score at baseline, Week 12, and Week 24. Used to assess differential treatment effects by baseline symptom cluster .
Time frame: Baseline, 12 weeks, 24 weeks
Change in DePaul Symptom Questionnaire (DSQ) score
Assesses symptom burden using the DSQ at baseline, Week 12, and Week 24.
Time frame: Baseline, 12 weeks, 24 weeks
Change in Pittsburgh Sleep Quality Index (PSQI) global score
Assesses sleep quality using the PSQI at baseline, Week 12, and Week 24. Scores (0-21)
Time frame: Baseline, 12 weeks, 24 weeks
Change in Brief Pain Inventory (BPI) severity score
Assesses pain severity using the BPI at baseline, Week 12, and Week 24. Scores (1-10).
Time frame: Baseline, 12 weeks, 24 weeks
Change in Modified Medical Research Council (mMRC) Dyspnea Scale score
Assesses dyspnea using the mMRC scale at baseline, Week 12, and Week 24. Score range 0-4
Time frame: Baseline, 12 weeks, 24 weeks
Change in Generalized Anxiety Disorder-7 (GAD-7) score
Assesses anxiety symptoms using the GAD-7 at baseline, Week 12, and Week 24. Score range 0-21
Time frame: Baseline, 12 weeks, 24 weeks
Change in Patient Health Questionnaire-8 (PHQ-8) score
Assesses depressive symptoms using the PHQ-8 at baseline, Week 12, and Week 24. Score range 0-24
Time frame: Baseline, 12 weeks, 24 weeks
Change in Brief Illness Perception Questionnaire (B-IPQ) total score
Assesses illness perception using the B-IPQ at baseline, Week 12, and Week 24. Score range 0-80
Time frame: Baseline, 12 weeks, 24 weeks
Change in Functional Capacity Scale (FUNCAP) score
Assesses functional impairment using the FUNCAP scale at baseline, Week 12, and Week 24. Score range 0-100
Time frame: Baseline, 12 weeks, 24 weeks.
Change in Composite Symptom Burden Index (CSBI) score
The CSBI is a derived score summarizing symptom burden across multiple validated domains (e.g., fatigue, pain, sleep, mood, cognitive function). Domain scores are standardized and averaged to produce a single CSBI value per participant. Paired differences from baseline to Week 12 and Week 24 will be analyzed to assess intra-individual changes and overall cohort-level trends.
Time frame: Baseline, 12 weeks, 24 weeks