Clinical trial NCT05877508: Anti-SARS-CoV-2 Monoclonal Antibodies for Long COVID (COVID-19)
Official title: An Exploratory, Randomized, Double-Blind Placebo-Controlled Study to Assess the Safety of an Anti-SARS-CoV-2 Monoclonal Antibody and Response to Treatment in Individuals With Long COVID (outSMART-LC)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Long COVID
Post-Acute Sequela of COVID-19
Post-Acute COVID-19
Keywords: COVID-19
Long COVID
Post-acute Sequelae of SARS-CoV-2 infection
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Aerium Therapeutics
name: Patient-Led Research Collaborative
name: PolyBio Research Foundation
First posted: 2023-05-26
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Persistent viral infection with viral reservoirs and detection of circulating spike protein after the initial acute illness is one potential pathogenic mechanism for Long COVID. This mechanism may be able to be targeted by SARS-CoV-2 monoclonal antibodies (mAbs). This trial will study the safety and efficacy of AER002 to treat individuals with Long COVID in an adult population.

Detailed description: The study will enroll approximately 30 participants who meet the World Health Organization (WHO) Long COVID criteria, with Long COVID attributed to a SARS-CoV-2 variant susceptible to AER002. Participants will be enrolled at a single center and randomized 2:1 to receive a SARS-CoV-2 monoclonal antibody (AER002) 1200mg or placebo. Evaluations will take place at baseline and at timepoints up to 1-year post-infusion.

Eligibility criteria: Key Inclusion Criteria (note, additional eligibility criteria not listed here will be assessed at Screening):

* Male, female, or transgender ≥18 years of age at Screening.
* History of confirmed acute SARS-CoV-2 infection.
* Long COVID attributed to a SARS-CoV-2 infection with a variant against which AER002 is known to have neutralizing activity (prior to August 15, 2022). Note: While individuals re-infected with SARS-CoV-2 after August 15, 2022 will not be excluded, the SARS-CoV-2 infection after which Long COVID symptoms began must pre-date August 15, 2022.
* At least two symptoms that are new or worsened since the time of SARS-CoV-2 infection, not known to be attributable to another cause upon assessment by the PI. Symptoms must have been present for at least 60 days prior to screening and must be reported to be at least somewhat bothersome.
* Body mass index (BMI) 18 to 50 kilograms/meter squared (kg/m2), inclusive, at the time of screening.
* Participants who are of childbearing potential (CBP) and male participants with sexual partner(s) who are females of CBP must agree to use adequate contraception from study consent through 360 days after dosing.

Key Exclusion Criteria (note, additional eligibility criteria not listed here will be assessed at Screening):

* Long COVID attributed to a SARS-CoV-2 infection after August 15, 2022.
* Previously received treatment or prophylaxis with a SARS-CoV-2-specific mAb, or plan to receive such treatment before exiting the study.
* Previously received COVID-19 convalescent plasma treatment within 60 days prior to Day 0 or plan to receive such treatment before exiting the study.
* Plans to receive any investigational or approved vaccine or booster for SARS-CoV-2 within 60 days prior to Day 0 or before Day 30 following Day 0.
* Active cardiovascular disease or recent (within 3 months) stroke.
* Recent (within 6 months) or planned major surgery.
* Currently hospitalized or recent (within 1 month) unplanned hospitalization.
* Active Hepatitis Bor C infection .
* Untreated or unstable HIV infection (two or more consecutive plasma HIV RNA values \>48 copies/mL in the 6 months prior to screen).
* Severe coagulopathy (international normalized ratio ((INR) \>2.0, history of hemophilia).
* Severe anemia (hemoglobin \<9 grams/deciliter (g/dL)).
* Moderate or severe immunocompromise, according to the current NIH COVID-19 Treatment Guidelines as of March 6, 2023.
* History of anaphylaxis or hypersensitivity upon receiving IV antibody infusions, any componenets of the intervention, prescription or non-prescription drugs, or food products in the past.
* Pregnant, breastfeeding, or unwilling to practice birth control abide by the contraception requirements outlined in the inclusion criteria.
* Participation in a clinical trial with receipt of an investigational product within 28 days or 5 half-lives (whichever is longer) prior to Day 0.
* Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.

Primary outcomes:
measure: Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Physical Health Summary Score from Baseline.
timeFrame: Baseline and Day 90
Secondary outcomes:
measure: Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Physical Health Summary Score from Baseline.
timeFrame: Baseline to Day 30 and Day 180
measure: Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Mental Health Summary Score from Baseline.
timeFrame: Baseline to Day 90
measure: Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Mental Health Summary Score from Baseline.
timeFrame: Baseline to Day 30 and Day 180
measure: Change in Quality of Life (Global Health Score) on a 100-point Visual-Analogue Scale from Baseline
timeFrame: Baseline and Day 90
measure: Change in Quality of Life Score (5-Item EuroQol EQ-5D-5L) Index Value Score from Baseline.
timeFrame: Baseline to Day 90
measure: Change in Duke Activity Status Index (DASI) from Baseline
timeFrame: Baseline to Day 90
measure: Change in Composite Autonomic Symptom Score (COMPASS-31) Score from Baseline.
timeFrame: Baseline and Day 90
measure: Change in World Health Organization Disability Assessment Schedule 2.0 (WHO-DAS 2.0) questionnaire from Baseline
timeFrame: Baseline and Day 90
measure: Patient Global Impression of Change (PGIC) at D90
timeFrame: Day 90
measure: Change in Everyday Cognition Form (ECog-39) instrument from Baseline
timeFrame: Baseline and Day 90
measure: Change in 6 Minute Walking Test (6MWT) from Baseline
timeFrame: Baseline and Day 90
measure: Change in Active Stand Test from Baseline
timeFrame: Baseline and Day 90
measure: Change in Neurocognition Index (NCI) standard score from the CNS-VS from Baseline
timeFrame: Baseline and Day 90
measure: Change in CRP from Baseline
timeFrame: Baseline and Day 90
measure: Change in ESR from Baseline
timeFrame: Baseline and Day 90
measure: Change in D-Dimer from Baseline
timeFrame: Baseline and Day 90
measure: Change in Fibrinogen from Baseline
timeFrame: Baseline and Day 90
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF/Zuckerberg San Francisco General Hospital
state: California
Study officials:
affiliation: University of California, San Francisco
name: Michael J Peluso, MD
role: PRINCIPAL_INVESTIGATOR
References: