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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Pozelimab
* Drug: Cemdisiran


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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 Key Exclusion Criteria: 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 NOTE: Other protocol-defined Inclusion/ Exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |