Invivyd's Phase 3 CANOPY study is evaluating the clinical efficacy of pemivibart for the prevention of COVID-19. The study, presented at IDWeek 2024, is designed to assess the safety and efficacy of pemivibart in preventing symptomatic COVID-19 in two cohorts: individuals with moderate-to-severe immune compromise (Cohort A) and those at risk of SARS-CoV-2 exposure due to regular unmasked indoor interactions (Cohort B).
Pemivibart is an investigational half-life-extended mAb engineered from adintrevimab (ADG20), which previously demonstrated clinical efficacy against earlier SARS-CoV-2 variants. Pemivibart binds to the spike protein receptor binding domain (RBD) of SARS-CoV-2, interfering with the virus's ability to infect human cells.
CANOPY Study Design and Objectives
The CANOPY trial (NCT06039449) is a Phase 3 clinical trial evaluating the efficacy and safety of pemivibart for the prevention of COVID-19. In Cohort A, participants with moderate-to-severe immune compromise (N=306) received 4500 mg of pemivibart intravenously. Cohort B included participants at risk of SARS-CoV-2 exposure (N=484), randomized 2:1 to receive either 4500 mg of pemivibart intravenously (n=322) or placebo (n=162).
The primary objectives of Cohort A include evaluating protection against symptomatic COVID-19 based on serum virus neutralization antibody (sVNA) titers against SARS-CoV-2 after receiving pemivibart, using an immunobridging approach, and assessing the safety and tolerability of pemivibart. For Cohort B, the primary objective is to evaluate the safety and tolerability of pemivibart compared with placebo.
Additional objectives for both cohorts include evaluating pharmacokinetics (PK), antidrug antibody (ADA) responses, and prevention of RT-PCR-confirmed symptomatic COVID-19.
Exploratory Efficacy Endpoint
The study includes an exploratory efficacy endpoint focusing on RT-PCR-confirmed symptomatic COVID-19. Participants who presented with symptoms of COVID-19 were instructed to contact the study site team and report to the site within 2 days of symptom confirmation for collection of nasopharyngeal and saliva samples for central RT-PCR SARS-CoV-2 testing. Information regarding the duration and severity of COVID-19 symptoms was collected approximately 28 days after sample collection.
A positive central RT-PCR result for SARS-CoV-2 from a nasopharyngeal swab, saliva sample, and/or nasopharyngeal swab for a respiratory pathogen panel were included in the endpoint.
Baseline Demographics and Characteristics
Baseline demographics and characteristics of the study participants were reported. In Cohort A, the median age was 59 years (range 22-83), with 58.5% of participants being 55 years or older. In Cohort B, the median age was 47.5 years (range 18-84) for the pemivibart group and 48 years (range 19-78) for the placebo group.
In Cohort A, 61.1% of participants were female, while in Cohort B, 51.6% and 56.2% of participants were female in the pemivibart and placebo groups, respectively. The majority of participants in all cohorts were White (85.6% in Cohort A, 62.4% and 66.7% in Cohort B pemivibart and placebo groups, respectively).
Prior COVID-19 vaccination rates varied, with 87.9% of participants in Cohort A receiving any prior COVID-19 vaccine, compared to 58.7% and 61.7% in the pemivibart and placebo groups of Cohort B, respectively. The median number of vaccines received also differed, with 5 (range 1-11) in Cohort A, and 3 (range 1-6 and 1-5) in Cohort B pemivibart and placebo groups, respectively.
All participants in Cohort A had risk factors for COVID-19 disease progression due to being immunocompromised, while 66.1% and 61.7% of participants in Cohort B pemivibart and placebo groups, respectively, had risk factors for COVID-19 disease progression. These risk factors included age ≥55 years, obesity (BMI >30 kg/m2), diabetes, chronic kidney disease, chronic lung disease, and cardiac disease.
