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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Pozelimab; Drug: Cemdisiran

• Registration Number: NCT04601844
• Lead Sponsor: Regeneron Pharmaceuticals

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-10-21
• Study First Submitted QC: 2020-10-21
• Study First Posted: 2020-10-26
• Study Start: 2020-11-16
• Primary Completion: 2021-07-23
• Study Completion: 2021-07-23
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-11
• Last Update Posted: 2021-11-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1	Cemdisiran	Cemdisiran at dose 1 SC single dose on day 1 followed by pozelimab at dose 1 SC single dose on day 29
Cohort 3	Pozelimab	Cemdisiran at dose 2 SC single dose and pozelimab at dose 2 SC single dose, both administered on day 1
Cohort 3	Cemdisiran	Cemdisiran at dose 2 SC single dose and pozelimab at dose 2 SC single dose, both administered on day 1
Cohort 1	Pozelimab	Cemdisiran at dose 1 SC single dose on day 1 followed by pozelimab at dose 1 SC single dose on day 29
Cohort 2	Pozelimab	Cemdisiran at dose 2 SC single dose on day 1 followed by pozelimab at dose 1 SC single dose on day 29
Cohort 2	Cemdisiran	Cemdisiran at dose 2 SC single dose on day 1 followed by pozelimab at dose 1 SC single dose on day 29

Primary Outcome Measures

Name	Time	Method
Incidence and severity of treatment emergent adverse events (TEAEs)	Up to 20 weeks

Secondary Outcome Measures

Name	Time	Method
Concentrations of total C5 over time	Up to 20 weeks
Concentrations of pozelimab in serum over time	Up to 20 weeks
Concentrations of cemdisiran in plasma 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

Trial Locations

Locations (1)

Regeneron Research Site; 🇧🇪 Antwerp, Belgium