To Investigate Efficacy, Pharmacodynamics, and Safety of BC 007 in Participants With Long COVID

Study Overview
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Brief Summary
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This study is an interventional, randomized, multinational, multicenter, double-blind, phase 2 study with a follow-up period of circa 12 months. The intension of this clinical trial is to investigate the long-term sequelae (named Long COVID syndrome; post COVID or PASC) of an infection with Corona Virus Type 2 that has resulted in a condition known as Severe Acute Respiratory Syndrome Corona Virus Type 2 (SARS-CoV-2). The purpose of this study is to evaluate the efficacy and safety of BC 007 as a treatment for long-lasting COVID-symptoms in patients who were neither intubated nor supported with extracorporeal blood oxygenation (ECMO) during their acute COVID-19 infection. The study drug acts by neutralizing functional autoantibodies directed against G-protein coupled receptors (GPCRs). Neutralization of the autoantibodies is expected to induce a beneficial effect on symptoms typically seen in patients with long COVID syndrome. Functional autoantibodies are proteins belonging to the class of G-type immunoglobulins that can be synthesized by activation of the immune system and can induce various pathogenic activities by binding to one of the extracellular loops of G-proteins (GPCR-AAB). The study consists of a screening phase of up to 21 days, treatment (two administrations by intravenous infusion at two-week intervals either with the study drug (BC 007) or with placebo (NaCl 0.9%), with an initial follow-up period of 15 days after each administration and an extended follow-up period of 330 days. Patients are required to visit the study center for follow-up visits at specified intervals. For the entire study duration of 381 days from screening to the end of the study, 11 site visits are planned.

Official Title
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A Prospective, Double-blind, Randomized, Parallel Group, Placebo Controlled, Multicentre, Phase II Study to Investigate the Efficacy, GPCR Autoantibody Neutralizing Effect, Safety, and Tolerability of BC 007 in Participants With Long COVID

Conditions
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Long Covid

Intervention / Treatment
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* Drug: BC 007 or matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant provides written informed consent prior to any clinical study-specific procedures. The participant is a male or female, ≥18 years of age, at the time of signing the informed consent form. All male and female participants of childbearing potential must be willing to use effective methods of contraception during the intervention period, and at least 90 days from the time of receiving the last dose of the study intervention. Male participants must refrain from donating sperm during this period. Acute phase of COVID-19 ended at least 3 months prior to dosing. The participant has a confirmed negative SARS-CoV-2 test result (polymerase chain reaction [PCR] test) at screening. The participant has a previous positive SARS-CoV-2 test result (PCR test or documented rapid antigen test) not older than 12 months at screening and reported long COVID symptoms starting no later than 12 weeks after the first positive test and might have had a symptom-free interval between the acute phase of infection and the occurrence of long COVID symptoms as defined by the WHO. Participant is screened positive for GPCR-AAB activity. Participant has not been intubated or received ECMO support during their acute COVID-19 infection. Participant screens positive for fatigue (FACIT-F score <35) and presents with at least one additional symptom from the symptom score sheet (COA) which has persisted for more than 12 weeks. Participant is not on any permanent medication(s) to treat chronic diseases prior to COVID19 infection. Participant reports that his/her activity level was not impaired prior to acute COVID-19 infection. Exclusion Criteria: Any history or evidence of any clinically significant cardiovascular disease (specifically tachycardia including Postural Orthostatic Tachycardia Syndrome. Any history of gastrointestinal, endocrinologic (Type 1 diabetes,), haematologic, hepatic, immunologic, metabolic (specifically gout), urologic, pulmonary (asthma), neurologic, dermatologic, renal and/or other major disease or malignancy, as judged by the Investigator before SARS-CoV-2 infection. Participants with history of major active or chronic unstable psychiatric illness (e.g., but not limited to, depression, bipolar disorder, obsessive compulsive disorder, schizophrenia) within the previous year. Any history of any other chronic neurological, or psychological disease such as, but not limited to, chronic fatigue syndrome, fibromyalgia, lupus, Sjogren's syndrome; or history of allergic reactions, judged to be clinically significant by the Investigator. Participant has a history of hypersensitivity to the study intervention or any of the excipients or to medicinal products with similar chemical structures. Participant has any other condition, which in the opinion of the Investigator precludes the participant's participation in the clinical study. Participant shows clinically significant abnormalities in clinical chemistry or haematology at screening, as judged by the Investigator. Female participant is pregnant and/or breast feeding. Participant participated in a previous clinical study (within 30 days or 5 half-lives of the investigational drug, or whichever is longer) or concomitant participation in another clinical study with investigational medicinal product(s) or device(s). Participant is an employee of the Sponsor, or contract research organization (CRO) conducting the study. Participant has a close affiliation with the investigational site, e.g., a close relative of the Investigator, dependent person (e.g., employee or student of the investigational site). Participant with an estimated glomerular filtration rate <60 mL/min/1,73 m². Participant has alcohol addiction or history of alcohol addiction. Participant has drug addiction or history of drug addiction. Any psychological, emotional problems, any disorders or resultant therapy that is likely to invalidate informed consent or limit the ability of the participant to comply with the protocol requirements. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the last 5 years. Participant has had comparable and prolonged symptoms after other viral infections (e.g., after Epstein-Barr virus infection, influenza, infectious mononucleosis). Previous diagnosis of sleep apnoea. Current use of medications with psychoactive properties that have a deleterious effect on cognition.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: double-blind, randomized, parallel group, placebo controlled, multicentric
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1350mg BC 007 solution for infusion for 75-minutes intravenous infusion<br> | Drug: BC 007 or matching placebo<br>* Participants will be treated with two infusions of BC 007 or placebo two weeks apart, according to a double-blind design<br>|
| Placebo Comparator: 0.9% NaCl solution for infusion for 75-minutes intravenous infusion<br> | Drug: BC 007 or matching placebo<br>* Participants will be treated with two infusions of BC 007 or placebo two weeks apart, according to a double-blind design<br>|
| Experimental: 1900mg BC 007 solution for infusion for 105-minutes intravenous infusion<br> | Drug: BC 007 or matching placebo<br>* Participants will be treated with two infusions of BC 007 or placebo two weeks apart, according to a double-blind design<br>|
| Placebo Comparator: 0.9% NaCl solution for infusion for 105-minutes intravenous infusion<br> | Drug: BC 007 or matching placebo<br>* Participants will be treated with two infusions of BC 007 or placebo two weeks apart, according to a double-blind design<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in score on FACIT-F scale at Day 30. | To compare efficacy of BC 007 (double dose 1350 mg and double dose 1900 mg) with placebo based on Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale in long COVID participants. FACIT-F is a five-point scale from 0 (not at all) to 4 (very much). The maximum composite scale is 52 (range 0 to 52). Higher scores mean a better outcome. | Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare GPCR AAB neutralizing effect of BC 007 1350 mg with that of placebo. | Proportion of participants sero-converting to negative for GPCR-AAB | at Days 3, 15, 17, 30, 90, 180 and Day 360 post first infusion of study intervention. | 
| To compare GPCR AAB neutralizing effect of BC 007 1900 mg with that of placebo. | Proportion of participants sero-converting to negative for GPCR-AAB | at Days 3, 15, 17, 30, 90, 180 and Day 360 post first infusion of study intervention. | 
| To compare GPCR-AAB neutralizing effect of BC 007 1350 mg with that of BC 007 1900 mg | Proportion of participants sero-converting to negative for GPCR-AAB | at Days 3, 15, 17, 30, 90, 180 and Day 360 post first infusion of study intervention. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Long Covid, Autoantibodies, Post-acute COVID-19 syndrome, BC 007, PASC