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

Phase 2Active Not RecruitingNCT05877508

Michael Peluso, MD36 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

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

Interventions

AER002DRUG

Intravenous infusion of AER002

PlaceboOTHER

Placebo infusion

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (1)

UCSF/Zuckerberg San Francisco General Hospital

San Francisco, California, United States

Outcomes

Primary Outcomes

Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Physical Health Summary Score

This measure will evaluate whether there is a difference between treatment with AER002 versus placebo in baseline adjusted mean PROMIS-29 Physical Health Summary Score at Day 90 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). A T-score is calculated from each individual domain. A T score of 50 represents the mean for US general adult population, and 10 is the standard deviation. A lower T score indicates worse physical health.

Time frame: Day 90

Secondary Outcomes

Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Physical Health Summary Score

This measure will evaluate whether there is a difference between treatment with AER002 versus placebo in baseline adjusted mean PROMIS-29 Physical Health Summary Score at Day 30 and Day 180 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). A T-score is calculated from each individual domain. A T score of 50 represents the mean for US general adult population, and 10 is the standard deviation. A lower T score indicates worse physical health.

Time frame: Day 30 and Day 180

Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Mental Health Summary Score

This measure will evaluate whether there is a difference between treatment with AER002 versus placebo in baseline adjusted mean PROMIS-29 Mental Health Summary Score at Day 90 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). A T-score is calculated from each individual domain. A T score of 50 represents the mean for US general adult population, and 10 is the standard deviation. A lower T score indicates worse mental health.

Data from ClinicalTrials.gov

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Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Mental Health Summary Score

This measure will evaluate whether there is a difference between treatment with AER002 versus placebo in baseline adjusted mean PROMIS-29 Mental Health Summary Score at Day 30 and Day 180 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). A T-score is calculated from each individual domain. A T score of 50 represents the mean for US general adult population, and 10 is the standard deviation. A lower T score indicates worse mental health.

Time frame: Day 30 and Day 180

Quality of Life (Global Health Score) 100-point Visual-Analogue Scale

This measure will evaluate whether there is a difference between treatment with AER002 versus placebo in the baseline adjusted mean Quality of Life 100-point Visual-Analogue-Scale at Day 90 post-infusion. 0 represents the worst health a person can imagine and 100 represents the best health a person can imagine.

Time frame: Day 90

Quality of Life (5-Item EuroQol EQ-5D-5L) Index Value Score

This measure will evaluate whether there is a difference between treatment with AER002 versus placebo in baseline adjusted mean Quality of Life (5-Item EuroQol EQ-5D-5L) Index Value Score at Day 90 post-infusion. 5-Item EuroQol EQ-5D-5L questions assess pain/difficulty in day-to-day activities over the past week. The 5-Item EuroQol EQ-5D-5L produces a score that typically ranges from 0 - 1, with a higher score indicating better quality of life.

Time frame: Day 90

Duke Activity Status Index (DASI)

This measure will evaluate whether there is a difference between treatment with AER002 versus placebo in baseline adjusted mean DASI at Day 90 post-infusion. The Duke Activity Status Index is a patient-reported estimate of functional capacity, maximal oxygen consumption (VO2 max) and maximum metabolic equivalent of tasks (METs). The DASI questionnaire produces a score between 0 and 58.2 points, which is linearly correlated with a patient's VO2 max and METs, as measured from cardiopulmonary exercise testing (CPET). It inquires about a person's ability to perform self-care, walk, climb stairs, run, do house and yard work, engage in sexual intercourse, and perform moderate recreational activities. A higher score indicates higher functional capacity.

Time frame: Day 90

Composite Autonomic Symptom Score-31 (COMPASS-31)

This measure will evaluate whether there is a difference between treatment with AER002 versus placebo in baseline adjusted mean COMPASS-31 score at Day 90 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. The total score ranges from 0 to 100 and a higher score indicates more severe autonomic dysfunction.

Time frame: Day 90

World Health Organization Disability Assessment Schedule 2.0 (WHO-DAS 2.0)

This measure will evaluate whether there is a difference between treatment with AER002 versus placebo in baseline adjusted mean WHO-DAS 2.0 score at Day 90 post-infusion. The World Health Organization Disability Assessment Schedule 2.0 questionnaire asks about difficulties due to health conditions. Health conditions include diseases or illnesses, other health problems that may be short or long lasting, injuries, mental or emotional problems, and problems with alcohol or drugs. The range is scored from 0-48, with a higher score indicating a higher level of disability.

Time frame: Day 90

Patient Global Impression of Change (PGIC) Scale

This measure will evaluate whether there is a difference between treatment with AER002 versus placebo on the Patient Global Impression of Change (PGIC) scale at Day 90 post-infusion. The self-reported PGIC reflects a patient's belief about the efficacy of treatment. We used a modified PGIC scale which has been used to study pain syndromes and has been employed in other Long COVID clinical trials. It is a common data element developed by the National Institutes of Mental Health. The PGIC ranges from 0 (Much better) to 10 (Much Worse). A score of 5 indicates no change.

Time frame: Day 90

Everyday Cognition Form (ECog-39)

This measure will evaluate whether there is a difference between treatment with AER002 versus placebo in baseline adjusted mean ECog-39 score at Day 90 post-infusion. The ECog-39 is an instrument that measures the decline in everyday cognitive and functional abilities that map to six cognitive domains, adapted specifically to describe change in abilities since having COVID. A summary ECog-39 score is calculated scored with a range of 1-4, with a higher score indicating greater cognitive impairment.

Time frame: Day 90

6 Minute Walking Test (6MWT)

This measure will evaluate whether there is a difference between treatment with AER002 versus placebo in baseline adjusted mean distance walked on the 6MWT at Day 90 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.

Time frame: Day 90

Active Stand Test

The active standing test is a non-invasive tool to assess orthostatic hypotension (OH) and postural orthostatic tachycardia syndrome (POTS). In short, blood pressure and heart rate measurements were obtained after 5 minutes of resting supine and 1, 3, 5, and 10 minutes of continuous standing. Abnormal active standing test results were defined as those with a decline of \>20 mmHg in systolic or \> 10 mmHg in diastolic blood pressure in at least two consecutive measurements, or those with an increase in heart rate \> 30 bpm on two consecutive measurements.

Time frame: Day 90

Neurocognition Index (NCI) Standard Score From the CNS-VS

This measure will evaluate whether there is a difference between treatment with AER002 versus placebo in baseline adjusted mean NCI standard score from the CNS-VS at Day 90 post-infusion. The CNS Vital Signs is a a computer-based neurocognitive assessment comprised of seven tests: verbal and visual memory, finger tapping, symbol digit coding, the Stroop Test, a test of shifting attention and the continuous performance test. The battery gives a summary neurocognition index (NCI) score averaging five domain scores (Composite Memory, Psychomotor Speed, Reaction Time, Complex Attention, and Cognitive Flexibility) and representing a global score of neurocognition. NCI scores are normalized scores (mean 100, standard deviation 15) that are age matched relative to other people in a normative sample. A higher score indicates better cognitive function.

Time frame: Day 90

C-Reactive Protein (CRP)

This measure will evaluate whether there is a difference between treatment with AER002 versus placebo in baseline adjusted mean CRP concentration (mg/L) at Day 90 post-infusion.

Time frame: Day 90

Erythrocyte Sedimentation Rate (ESR)

This measure will evaluate whether there is a difference between treatment with AER002 versus placebo in baseline adjusted mean ESR at Day 90 post-infusion.

Time frame: Day 90

D-Dimer

This measure will evaluate whether there is a difference between treatment with AER002 versus placebo in baseline adjusted mean D-Dimer at Day 90 post-infusion.

Time frame: Day 90

Fibrinogen

This measure will evaluate whether there is a difference between treatment with AER002 versus placebo in baseline adjusted mean fibrinogen concentration (mg/dL) at Day 90 post-infusion.

Time frame: Day 90