A Study to Examine the Safety, Tolerability and Biological Effects of Single Doses of Subcutaneously and Intravenously Administered Pozelimab as Monotherapy and in Combination With Single Doses of Subcutaneously Administered Cemdisiran in Adult Japanese Healthy Volunteers

An Open-Label Parallel-Dose Study of the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Single Doses of Subcutaneously and Intravenously Administered Pozelimab as Monotherapy and in Combination With Single Doses of Subcutaneously Administered Cemdisiran in Japanese Healthy Volunteers

The primary objective of the study is to assess the concentration-time profiles of total pozelimab, total C5, cemdisiran, and cemdisiran metabolite(s) in Japanese adult participants following single doses of intravenous (IV) and 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 evaluate the safety and tolerability of pozelimab alone and in combination with cemdisiran in healthy Japanese adult participants
• To assess the pharmacodynamic (PD) profile of pozelimab alone and in combination with cemdisiran in healthy Japanese adult participants
• To assess the immunogenicity of pozelimab and cemdisiran in healthy Japanese adult participants

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 1YR
    • Regeneron Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Japanese participant must be:

   1. Be Japanese, born in Japan, and have both biologic parents and 4 biologic grandparents who are ethnically Japanese and born in Japan
   2. Have maintained a Japanese lifestyle, with no significant change since leaving Japan, including having access to Japanese food and adhering to a Japanese diet
   3. Living < 10 years outside of Japan
2. Has a Body Mass Index (BMI) between 18 and 30 kg/m2 (inclusive) at screening visit
3. Is judged by the investigator to be in good health based on medical history, physical examination, vital sign measurements, and ECGs performed at screening and/or prior to administration of initial dose of study drug
4. Is in good health based on laboratory safety testing obtained at the screening visit Note: Participant with suspected or confirmed Gilbert's disease can be enrolled in the study
5. Willing to undergo vaccination against N. meningitidis unless participant has documentation of completed series of vaccinations within the past 2 years of the screening visit
6. Must have two consecutive negative COVID-19 tests at least 48 hours apart and within 7 days prior to study drug administration Note: The test may be the point of care quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) test or approved COVID-19 antigen test at the discretion of the investigator.

Key Exclusion Criteria:

1. History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric or neurological disease, as assessed by the investigator as defined in the protocol
2. Presents any concern to the study investigator that might confound the results of the study or poses an additional risk to the participant by their participation in the study
3. Hospitalization (>24 hour) for any reason within 30 days of the screening visit
4. Has a confirmed positive drug test result at the screening visit and/or prior to enrollment; or a history of alcohol and/or drug abuse within a year prior to the screening visit
5. Is positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb) at the screening visit
6. Is positive for hepatitis C antibody and positive for qualitative (i.e., detected) hepatitis C virus (HCV) RNA test at the screening visit
7. Within the previous 2 months of the screening visit has a history of bacterial, protozoal, viral or parasite infection (including COVID-19) and/or persistent chronic or active recurring infection which require treatment with antibiotics, antivirals, or antifungals
8. Known or suspected COVID-19 disease at screening and/or prior to 1st dose administration

NOTE: Other protocol-defined Inclusion and 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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Pozelimab: Single-dose SC on day 1	Drug: Pozelimab; Administered intravenous (IV) or subcutaneous (SC) per protocol; Other Names: REGN3918
Experimental: Cohort 2; Pozelimab: Single-dose IV on day 1	Drug: Pozelimab; Administered intravenous (IV) or subcutaneous (SC) per protocol; Other Names: REGN3918
Experimental: Cohort 3; Pozelimab: Single-dose SC on day 29 Cemdisiran: Single-dose SC on day 1	Drug: Cemdisiran; Administered SC per protocol; Other Names: ALN-CC5; Drug: Pozelimab; Administered intravenous (IV) or subcutaneous (SC) per protocol; Other Names: REGN3918
Experimental: Cohort 4; Pozelimab: Single-dose SC on day 1 Cemdisiran: Single-dose SC on day 1	Drug: Cemdisiran; Administered SC per protocol; Other Names: ALN-CC5; Drug: Pozelimab; Administered intravenous (IV) or subcutaneous (SC) per protocol; Other Names: REGN3918
Experimental: Cohort 5; Optional Pozelimab: Single-dose SC on day 1 or day 29 Cemdisiran: Single-dose SC on day 1	Drug: Cemdisiran; Administered SC per protocol; Other Names: ALN-CC5; Drug: Pozelimab; Administered intravenous (IV) or subcutaneous (SC) per protocol; Other Names: REGN3918
Experimental: Cohort 6; Pozelimab: Single-dose IV on day 1	Drug: Pozelimab; Administered intravenous (IV) or subcutaneous (SC) per protocol; Other Names: REGN3918

What is the study measuring?

Primary 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

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of treatment-emergent anti-drug antibodies (ADA) to pozelimab	Up to 20 weeks
The incidence and severity of treatment-emergent adverse events (TEAE) in subjects administered pozelimab with/without cemdisiran	Up to 20 weeks
Concentrations of total C5 in plasma over time	Up to 20 weeks
Change from baseline in CH50 over time	Up to 20 weeks
Incidence of treatment-emergent ADA to cemdisiran	Up to 20 weeks

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2021
• Primary Completion (Actual): June 22, 2022
• Study Completion (Actual): June 22, 2022

Study Registration Dates

• First Submitted: June 17, 2021
• First Submitted That Met QC Criteria: June 17, 2021
• First Posted (Actual): June 25, 2021

Study Record Updates

• Last Update Posted (Actual): July 6, 2022
• Last Update Submitted That Met QC Criteria: July 1, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: R3918-HV-20117; 2021-001794-23 (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; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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