Clinical trial NCT04519437: Study Assessing the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Repeated Subcutaneous Doses of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies (REGN10933+REGN10987) in Adult Volunteers as Related to COVID-19
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study Assessing the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Repeated Subcutaneous Doses of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies (REGN10933+REGN10987) in Adult Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Chronic Stable Illness
Keywords: Coronavirus disease 2019 (COVID-19)
Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2)
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-08-19
Enrollment: 974
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objectives are:

* To assess the occurrence of adverse events of special interest (AESIs) in participants treated with repeated subcutaneous (SC) doses of REGN10933+REGN10987 compared to placebo
* To assess the concentrations of REGN10933 and REGN10987 in serum over time after single and repeated SC administration

The secondary objectives are:

* To assess the safety and tolerability of repeated SC doses of REGN10933+REGN10987 compared to placebo
* To assess attainment of target concentrations of REGN10933 and REGN10987 in serum after single and repeated SC administration
* To assess the immunogenicity of REGN10933 and REGN10987


Eligibility criteria: Key Inclusion Criteria:

1. Is healthy or has chronic medical condition(s) that is stable and well controlled as per the opinion of the investigator and is not likely to require medical intervention through the end of study
2. Stable medication for co-morbid condition(s) for at least 6 months prior to screening
3. Willing and able to comply with study visits and study-related procedures, including compliance with site precautionary requirements related to SARS-CoV-2 infection and transmission

Key Exclusion Criteria:

1. Positive diagnostic test for SARS-CoV-2 infection ≤72 hours prior to randomization
2. Subject-reported clinical history of COVID-19 as determined by investigator
3. Subject-reported history of prior positive diagnostic test for SARS-CoV-2 infection
4. Active respiratory or non-respiratory symptoms suggestive or consistent with COVID-19
5. Medically attended acute illness, systemic antibiotics use, or hospitalization (ie, \>24 hours) for any reason within 30 days prior to screening
6. Acute exacerbation of a chronic pulmonary condition (eg, chronic obstructive pulmonary disease \[COPD\], asthma exacerbations) in the past 6 months prior to screening
7. Received investigational or approved SARS-CoV-2 vaccine
8. Received investigational or approved passive antibodies for SARS-CoV-2 infection prophylaxis as defined in the protocol
9. Use of remdesivir, intravenous immunoglobulin (IVIG), or other anti-SARS viral agents within 2 months prior to screening

NOTE: Other protocol-defined Inclusion/ Exclusion criteria apply

Primary outcomes:
measure: Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration
timeFrame: Within 4 days postdose at Baseline
measure: Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration
timeFrame: Within 4 days postdose at Day 29
measure: Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration
timeFrame: Within 4 days postdose at Day 57
measure: Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration
timeFrame: Within 4 days postdose at Day 85
measure: Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration
timeFrame: Within 4 days postdose at Day 113
measure: Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration
timeFrame: Within 4 days postdose at Day 141
measure: Concentrations of REGN10933 in serum over time
timeFrame: Up to 52 weeks
measure: Concentrations of REGN10987 in serum over time
timeFrame: Up to 52 weeks
Secondary outcomes:
measure: Proportion of participants with treatment-emergent adverse events (TEAEs)
timeFrame: Up to 52 weeks
measure: Severity of TEAEs
timeFrame: Up to 52 weeks
measure: Proportion of participants who achieve or exceed target concentration in serum of REGN10933
timeFrame: Up to 52 weeks
measure: Proportion of participants who achieve or exceed target concentration in serum of REGN10987
timeFrame: Up to 52 weeks
measure: Immunogenicity as measured by anti-drug antibodies (ADA) to REGN10933
timeFrame: Up to 52 weeks
measure: Immunogenicity as measured by anti-drug antibodies (ADA) to REGN10987
timeFrame: Up to 52 weeks
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Regeneron Study Site
state: Arizona
city: Rogers
country: United States
facility: Regeneron Study Site
state: Arkansas
city: Sacramento
country: United States
facility: Regeneron Study Site
state: California
city: Miami
country: United States
facility: Regeneron Study Site
state: Florida
city: Lincoln
country: United States
facility: Regeneron Study Site
state: Nebraska
city: Dayton
country: United States
facility: Regeneron Study Site
state: Ohio
city: Austin
country: United States
facility: Regeneron Study Site
state: Texas
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: Hirsch C, Park YS, Piechotta V, Chai KL, Estcourt LJ, Monsef I, Salomon S, Wood EM, So-Osman C, McQuilten Z, Spinner CD, Malin JJ, Stegemann M, Skoetz N, Kreuzberger N. SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19. Cochrane Database Syst Rev. 2022 Jun 17;6(6):CD014945. doi: 10.1002/14651858.CD014945.pub2.
citation: Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.