Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Pozelimab in Combination With Cemdisiran in Healthy Adult Volunteers

An Open-Label, Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Doses of Subcutaneously Administered Human Monoclonal Antibody Pozelimab in Combination With Single Doses of Subcutaneously Administered siRNA Cemdisiran in Healthy Volunteers

The primary objective of the study is to evaluate the safety and tolerability of ascending doses of subcutaneous (SC) pozelimab and SC cemdisiran when administered on the same day or sequentially 28 days apart.

The secondary objectives of the study are:

• To assess the concentration-time profiles of total pozelimab, total complement component 5 (C5), cemdisiran, and cemdisiran metabolite(s) following single ascending doses of SC pozelimab and SC cemdisiran when administered on the same day or sequentially 28 days apart
• To assess the pharmacodynamic (PD) profile of ascending doses of SC pozelimab and SC cemdisiran, as well as when administered on the same day or sequentially 28 days apart
• To assess the immunogenicity of pozelimab and cemdisiran

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Pozelimab; Drug: Cemdisiran

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium, B-2060
    • Regeneron Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Has a body mass index less than 30 kg/m2 at the screening visit
2. Judged to be in good health as defined in the protocol
3. Is in good health based on laboratory safety testing obtained at the screening visit NOTE: Subject with a history of Gilbert's disease can be enrolled in the study
4. Willing to undergo vaccination against Neisseria meningitidis unless subjects have documentation of completed series of vaccinations within the past 2 years of the screening visit
5. Must have two negative COVID-19 tests taken 48 hours apart and within 7 days prior to study drug administration

Key Exclusion Criteria:

1. History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric or neurological disease, as assessed by the investigator that may confound the results of the study or poses an additional risk to the subject by study participation
2. Hospitalization (>24 h) for any reason within 30 days of the screening visit
3. Has a confirmed positive drug test result at the screening visit and/or prior to enrollment; or a history of recreational drug use (eg, marijuana) and/or drug or alcohol abuse within a year prior to the screening visit
4. Is positive for HIV, hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb), hepatitis C antibody and positive for qualitative (ie, detected) HCV RNA test at the screening visit
5. Within the previous 2 months of the screening visit has a history of bacterial, protozoal, parasitic or viral infection (including COVID-19) and/or persistent chronic or active recurring infection which requires treatment with antibiotics, antivirals, or antifungals
6. Known or suspected COVID-19 disease
7. Known allergy or intolerance to penicillin class antibiotics or macrolides

NOTE: Other protocol-defined Inclusion/ Exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Cemdisiran at dose 1 SC single dose on day 1 followed by pozelimab at dose 1 SC single dose on day 29	Drug: Pozelimab; Single dose administered subcutaneously; Other Names: REGN3918; Drug: Cemdisiran; Single dose administered SC; Other Names: ALN-CC5
Experimental: Cohort 2; Cemdisiran at dose 2 SC single dose on day 1 followed by pozelimab at dose 1 SC single dose on day 29	Drug: Pozelimab; Single dose administered subcutaneously; Other Names: REGN3918; Drug: Cemdisiran; Single dose administered SC; Other Names: ALN-CC5
Experimental: Cohort 3; Cemdisiran at dose 2 SC single dose and pozelimab at dose 2 SC single dose, both administered on day 1	Drug: Pozelimab; Single dose administered subcutaneously; Other Names: REGN3918; Drug: Cemdisiran; Single dose administered SC; Other Names: ALN-CC5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of treatment emergent adverse events (TEAEs)	Up to 20 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Concentrations of pozelimab in serum over time	Up to 20 weeks
Concentrations of cemdisiran in plasma over time	Up to 20 weeks
Concentrations of total C5 over time	Up to 20 weeks
Change from baseline in total complement hemolytic activity assay (CH50) over time	Up to 20 weeks
Incidence of treatment-emergent anti-drug antibodies (ADA) to pozelimab	Up to 20 weeks
Incidence of treatment-emergent anti-drug antibodies (ADA) to cemdisiran	Up to 20 weeks

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Alnylam Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2020
• Primary Completion (Actual): July 23, 2021
• Study Completion (Actual): July 23, 2021

Study Registration Dates

• First Submitted: October 21, 2020
• First Submitted That Met QC Criteria: October 21, 2020
• First Posted (Actual): October 26, 2020

Study Record Updates

• Last Update Posted (Actual): November 12, 2021
• Last Update Submitted That Met QC Criteria: November 11, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: R3918-HV-1982; 2020-000300-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• IPD Sharing Time Frame: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No