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

• ClinicalTrials.gov Identifier: NCT05877508
• Recruitment Status: Active, not recruiting
• First Posted: May 26, 2023
• Last Update Posted: January 5, 2024
• Sponsor: Michael Peluso, MD
• Collaborators: Aerium Therapeutics; Patient-Led Research Collaborative; PolyBio Research Foundation
• Information provided by (Responsible Party): Michael Peluso, MD, University of California, San Francisco

Tracking Information

• First Submitted Date: May 24, 2023
• First Posted Date: May 26, 2023
• Last Update Posted Date: January 5, 2024
• Actual Study Start Date: August 1, 2023
• Estimated Primary Completion Date: July 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 24, 2023)

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).

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: November 3, 2023)

• 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.
• 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.
• CNS-Vital Signs Global Neurocognitive Index [ Time Frame: Baseline and 3 months post-infusion. ]
  This measure will evaluate whether there is a difference between treatment with AER002 versus placebo on CNS-Vital Signs neurocognitive testing performance between baseline and at 3 months post-infusion. CNS-VS is a computerized testing battery that participants will complete at baseline and follow-up visits. The global neurocognitive index is a summary score that comprises multiple domains.
• Global health score on a 100-point visual-analogue scale [ Time Frame: Baseline and 3 months post-infusion. ]
  This measure will evaluate whether there is a difference between treatment with AER002 versus placebo on self-reported score on a 100-point visual-analogue scale, where 0 represents the worst health a person can imagine and 100 represents the best health a person can imagine.

Original Other Pre-specified Outcome Measures (submitted: May 24, 2023)

• 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.
• 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.

Descriptive Information

• Brief Title: 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)
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Long COVID
• Post-Acute Sequela of COVID-19
• Post-Acute COVID-19

Intervention

• Drug: AER002
  Intravenous infusion of AER002
• Other: Placebo
  Placebo infusion

Study Arms

• Experimental: AER002
  AER002 1200mg administered once by IV
  Intervention: Drug: AER002
• Placebo Comparator: Placebo
  Placebo administered once by IV
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: May 24, 2023): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 31, 2025
• Estimated Primary Completion Date: July 31, 2025 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05877508
• Other Study ID Numbers: 23-38629
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Michael Peluso, MD, University of California, San Francisco
• Original Responsible Party: Same as current
• Current Study Sponsor: Michael Peluso, MD
• Original Study Sponsor: Same as current

Collaborators

• Aerium Therapeutics
• Patient-Led Research Collaborative
• PolyBio Research Foundation

Investigators

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

• PRS Account: University of California, San Francisco
• Verification Date: January 2024