A Study to Examine the Safety, Tolerability and Biological Effects of REGN4461 in Healthy Volunteers
- Registration Number
- NCT03530514
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
The primary objective of the study is to evaluate the safety and tolerability of REGN4461 in healthy participants. The secondary objectives of the study are to:
* Characterize the Pharmacokinetic (PK) profile of single and repeated doses of REGN4461 and evaluate the effects of baseline covariates on PK profile
* Estimate the effects of repeated doses of REGN4461 on body weight over 12 weeks in overweight and obese participants
* Assess the effects of repeated doses of REGN4461 on ad lib energy intake in overweight and obese participants
* Evaluate the effects of single and repeated doses of REGN4461 on soluble forms of lipid-regulating proteins levels over time
* Assess the immunogenicity of single and repeated doses of REGN4461
- Detailed Description
This is a 2-part study of the safety, tolerability, PK and pharmacodynamic (PD) of single and repeated doses of REGN4461 in healthy participants. In Part A, healthy lean or overweight participants will be enrolled to evaluate the safety, tolerability, PK, and PD of single ascending intravenous (IV) and subcutaneous (SC) doses. Interim PK and safety information from Part A will be used to select the dose level, frequency, and mode of administration (IV or SC) for repeat dosing in Part B. In Part B, overweight/obese participants with body mass index (BMI) 25-40 kg/m2 will be enrolled to evaluate the safety, tolerability, PK, and PD of repeated doses of REGN4461 in 4 distinct cohorts defined by baseline leptin levels.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 113
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: Single dose cohort 1 REGN4461 Cohort 1 will receive a single IV dose of REGN4461 or matching placebo Part A: Single dose cohort 6 Placebo Cohort 6 will receive a sequential ascending single SC dose of REGN4461 or matching placebo Part A: Single dose cohort 1 Placebo Cohort 1 will receive a single IV dose of REGN4461 or matching placebo Part A: Single dose cohort 2 REGN4461 Cohort 2 will receive a sequential ascending single IV dose of REGN4461 or matching placebo Part A: Single dose cohort 2 Placebo Cohort 2 will receive a sequential ascending single IV dose of REGN4461 or matching placebo Part A: Single dose cohort 3 REGN4461 Cohort 3 will receive a sequential ascending single IV dose of REGN4461 or matching placebo Part A: Single dose cohort 3 Placebo Cohort 3 will receive a sequential ascending single IV dose of REGN4461 or matching placebo Part A: Single dose cohort 4 REGN4461 Cohort 4 will receive a sequential ascending single SC dose of REGN4461 or matching placebo Part A: Single dose cohort 4 Placebo Cohort 4 will receive a sequential ascending single SC dose of REGN4461 or matching placebo Part A: Single dose cohort 5 REGN4461 Cohort 5 will receive a sequential ascending single IV dose of REGN4461 or matching placebo Part A: Single dose cohort 5 Placebo Cohort 5 will receive a sequential ascending single IV dose of REGN4461 or matching placebo Part A: Single dose cohort 6 REGN4461 Cohort 6 will receive a sequential ascending single SC dose of REGN4461 or matching placebo Part A: Single dose cohort 7 REGN4461 Cohort 7 will receive a sequential ascending single IV dose of REGN4461 or matching placebo Part A: Single dose cohort 7 Placebo Cohort 7 will receive a sequential ascending single IV dose of REGN4461 or matching placebo Part A: Single dose cohort 8 REGN4461 Cohort 8 will receive a single IV dose of REGN4461 or matching placebo Part A: Single dose cohort 8 Placebo Cohort 8 will receive a single IV dose of REGN4461 or matching placebo Part A: Single dose cohort 9 REGN4461 Cohort 9 will receive a single IV dose of REGN4461 or matching placebo Part A: Single dose cohort 9 Placebo Cohort 9 will receive a single IV dose of REGN4461 or matching placebo Part B: Repeated dose cohort 10 REGN4461 Cohort 10 will receive repeated IV or SC doses of REGN4461 or matching placebo Part B: Repeated dose cohort 10 Placebo Cohort 10 will receive repeated IV or SC doses of REGN4461 or matching placebo
- Primary Outcome Measures
Name Time Method Number of treatment-emergent adverse events (TEAEs) Up to week 27
- Secondary Outcome Measures
Name Time Method Absolute change from baseline to week 12 in body weight in overweight or obese participants Baseline to week 12 Percent change from baseline to week 12 in body weight in overweight or obese participants Baseline to week 12 PK parameter: clearance (CL) Up to week 27 Pharmacokinetic (PK) parameter: Area under curve (AUC) computed from time zero to the time of the last positive concentration (AUClast) Up to week 27 PK parameter: trough concentration (Ctrough) Up to week 27 Concentrations of REGN4461 in serum over time Up to week 27 Incidence of anti-drug antibodies to REGN4461 over time after single doses of REGN4461 Up to week 16 Incidence of anti-drug antibodies to REGN4461 over time after repeated doses of REGN4461 Up to week 27 PK parameter: AUC computed across a dosing interval with length τ (AUCo-τ) Upt to week 27 PK parameter: peak concentration (Cmax) Up to week 27 PK parameter: time to Cmax (tmax) Up to week 27 Change from baseline in caloric intake in response to standardized meals in overweight or obese participants Baseline to week 12 Change in lipid-regulating protein levels over time after single doses of REGN4461 Up to week 16 Change in lipid-regulating protein levels over time after repeated doses of REGN4461 Up to week 27
Trial Locations
- Locations (1)
Regeneron Investigational Site
🇧🇪Antwerp, Belgium