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

NCT04601844 | Completed Phase 1

• 2 other identifiers: R3918-HV-19822020-000300-11
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of treatment emergent adverse events (TEAEs)

  Up to 20 weeks

Secondary Outcomes (6)

• 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

Study Arms (3)

Cohort 1

EXPERIMENTAL

Cemdisiran at dose 1 SC single dose on day 1 followed by pozelimab at dose 1 SC single dose on day 29

Drug: Pozelimab; Drug: Cemdisiran

Cohort 2

EXPERIMENTAL

Cemdisiran at dose 2 SC single dose on day 1 followed by pozelimab at dose 1 SC single dose on day 29

Drug: Pozelimab; Drug: Cemdisiran

Cohort 3

EXPERIMENTAL

Cemdisiran at dose 2 SC single dose and pozelimab at dose 2 SC single dose, both administered on day 1

Drug: Pozelimab; Drug: Cemdisiran

Interventions

Pozelimab DRUG

Single dose administered subcutaneously

Also known as: REGN3918

Cohort 1; Cohort 2; Cohort 3

Cemdisiran DRUG

Single dose administered SC

Also known as: ALN-CC5

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Has a body mass index less than 30 kg/m2 at the screening visit
• Judged to be in good health as defined in the protocol
• 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
• 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
• Must have two negative COVID-19 tests taken 48 hours apart and within 7 days prior to study drug administration

You may not qualify if:

• 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
• Hospitalization (\>24 h) for any reason within 30 days of the screening visit
• 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
• 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
• 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
• Known or suspected COVID-19 disease
• Known allergy or intolerance to penicillin class antibiotics or macrolides

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead
• Alnylam Pharmaceuticals: collaborator

Study Sites (1)

Regeneron Research Site

Antwerp, B-2060, Belgium

Location

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2020
• First Posted: October 26, 2020
• Study Start: November 16, 2020
• Primary Completion: July 23, 2021
• Study Completion: July 23, 2021
• Last Updated: November 12, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• 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.
• 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

Locations

BE (1)