Clinical trial NCT04601844: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Pozelimab in Combination With Cemdisiran in Healthy Adult Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Alnylam Pharmaceuticals
First posted: 2020-10-26
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Incidence and severity of treatment emergent adverse events (TEAEs)
timeFrame: Up to 20 weeks
Secondary outcomes:
measure: Concentrations of pozelimab in serum over time
timeFrame: Up to 20 weeks
measure: Concentrations of cemdisiran in plasma over time
timeFrame: Up to 20 weeks
measure: Concentrations of total C5 over time
timeFrame: Up to 20 weeks
measure: Change from baseline in total complement hemolytic activity assay (CH50) over time
timeFrame: Up to 20 weeks
measure: Incidence of treatment-emergent anti-drug antibodies (ADA) to pozelimab
timeFrame: Up to 20 weeks
measure: Incidence of treatment-emergent anti-drug antibodies (ADA) to cemdisiran
timeFrame: Up to 20 weeks
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Regeneron Research Site
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: