Anti-SARS-CoV-2 Monoclonal Antibodies for Long COVID (COVID-19) (outSMART-LC)

• ClinicalTrials.gov Identifier: NCT05877508
• Recruitment Status: Recruiting
• First Posted: May 26, 2023
• Last Update Posted: August 3, 2023
• Sponsor: Michael Peluso, MD
• Collaborator: Aerium Therapeutics
• Information provided by (Responsible Party): Michael Peluso, MD, University of California, San Francisco

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Long COVID; Post-Acute Sequela of COVID-19; Post-Acute COVID-19	Drug: AER002; Other: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: August 1, 2023
• Estimated Primary Completion Date: July 31, 2025
• Estimated Study Completion Date: July 31, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: AER002; AER002 1200mg administered once by IV	Drug: AER002; Intravenous infusion of AER002
Placebo Comparator: Placebo; Placebo administered once by IV	Other: Placebo; Placebo infusion

Outcome Measures

Primary Outcome Measures :

1. Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Score from Baseline. [ Time Frame: Baseline and 3 months post-infusion. ]
   This measure will evaluate whether there is a difference between treatment with AER002 versus placebo on the PROMIS-29 scale between baseline and 3 months post-infusion. PROMIS-29 is a validated scale assessing physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social activities, and pain. Each domain is scored on a 5-point scale (without any difficulty, with a little difficulty, with some difficulty, with much difficulty, unable to do).

Other Outcome Measures:

1. Change in Composite Autonomic Symptom Score (COMPASS-31) Score from Baseline. [ Time Frame: Baseline and 3 months post-infusion. ]
   This measure will evaluate whether there is a difference between treatment with AER002 versus placebo on the COMPASS-31 scale between baseline and 3 months post-infusion. COMPASS-31 asks 31 questions related to autonomic dysfunction. The answer to each question generates a numeric score for the question, which is then summed at the end of the questionnaire. A total score out of 100 is generated summarizing orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, urinary, pupillomotor, temperature intolerance, and sexual impairment.
2. Distance walked on 6 minute walk test (6MWT). [ Time Frame: Baseline and 3 months post-infusion. ]
   This measure will evaluate whether there is a difference between treatment with AER002 versus placebo on 6MWT performance between baseline and at 3 months post-infusion. The 6MWT requires an individual to walk at their normal pace for 6 minutes on a marked track (for example, a hallway). Vital signs are assessed, and the total distance covered is the primary outcome of interest.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• 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:

• 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.

Contacts and Locations

Contacts

Contact: Michael J Peluso, MD; 414-476-4082 ext 119; michael.peluso@ucsf.edu

Contact: Study Email; outsmartLC@ucsf.edu

Locations

United States, California

UCSF/Zuckerberg San Francisco General Hospital; Recruiting

San Francisco, California, United States, 94110

Contact: UCSF Study Team 415-476-4082 ext 144 outsmartLC@ucsf.edu

Principal Investigator: Michael J Peluso, MD

Sub-Investigator: Steven G Deeks, MD

Sub-Investigator: Timothy J Henrich, MD

Sub-Investigator: Priscilla Y Hsue, MD

Sponsors and Collaborators

Michael Peluso, MD

Aerium Therapeutics

Investigators

• Principal Investigator: Michael J Peluso, MD; University of California, San Francisco

More Information

• Responsible Party: Michael Peluso, MD, Assistant Professor, Medicine, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT05877508
• Other Study ID Numbers: 23-38629
• First Posted: May 26, 2023
• Last Update Posted: August 3, 2023
• Last Verified: August 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Michael Peluso, MD, University of California, San Francisco:

COVID-19; Long COVID; Post-acute Sequelae of SARS-CoV-2 infection

Additional relevant MeSH terms:

COVID-19; Post-Acute COVID-19 Syndrome; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes