Healthy Volunteers
Conditions
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.
Interventions
DRUGREGN4461
REGN4461
DRUGPlacebo
Placebo-matching REGN4461
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria Part A: * Males and females 18 to 50 years of age, inclusive * Body mass index (BMI) from 18.5 to \<30.0 kg/m\^2 * Participant is judged by the investigator to be in good health and free from major comorbidities based on medical history, physical examination, laboratory safety tests performed at screening and/or prior to administration of initial dose of study drug Part B: * Males and females 18 to 65 years of age, inclusive * Have a body mass index (BMI) from 25.0 to 40.0 kg/m\^2 * Participant is judged by the investigator to be free from major comorbidities based upon medical history, physical examination, laboratory safety tests performed at screening and/or prior to administration of initial dose of study drug. Participants can have a history of mild hyperlipidemia and/or mild hypertension but should be on stable doses of lipid lowering or blood pressure lowering medicines for at least 2 months prior to screening Key
Exclusion criteria
Part A: * History of type 1 or 2 diabetes or prediabetes or with fasting blood glucose (FBG) at screening ≥ 100mg/dL or with HbA1c at screening of ≥ 5.7%. * Fasting LDL-C ≥ 130mg/dL, TG ≥ 250 mg/dL Part B: * History of type 1 or 2 diabetes or with FBG at screening ≥ 126 mg/dL or with HbA1c at screening of ≥ 6.5%. A diagnosis of pre-diabetes is allowed. * Fasting LDL-C ≥ 160 or TG ≥ 500 mg/dL Key
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of treatment-emergent adverse events (TEAEs) | Up to week 27 |
Secondary
| Measure | Time frame |
|---|---|
| Concentrations of REGN4461 in serum over time | Up to week 27 |
| Percent change from baseline to week 12 in body weight in overweight or obese participants | Baseline to week 12 |
| Absolute change from baseline to week 12 in body weight in overweight or obese participants | Baseline to week 12 |
| 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 |
| 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 |
| 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: 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 |
| PK parameter: clearance (CL) | Up to week 27 |
| PK parameter: trough concentration (Ctrough) | Up to week 27 |
Countries
Belgium
Outcome results
None listed