A Study to Examine the Safety, Tolerability and Biological Effects of REGN4461 in Healthy Volunteers

NCT03530514 | Completed Phase 1

• 2 other identifiers: R4461-HV-17942018-000327-14
• Study Type: interventional
• Target: 113
• Locations: 1 country
• Sites: 1

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

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Number of treatment-emergent adverse events (TEAEs)

  Up to week 27

Secondary Outcomes (14)

• 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

Study Arms (10)

Part A: Single dose cohort 1

EXPERIMENTAL

Cohort 1 will receive a single IV dose of REGN4461 or matching placebo

Drug: REGN4461; Drug: Placebo

Part A: Single dose cohort 2

EXPERIMENTAL

Cohort 2 will receive a sequential ascending single IV dose of REGN4461 or matching placebo

Drug: REGN4461; Drug: Placebo

Part A: Single dose cohort 3

EXPERIMENTAL

Cohort 3 will receive a sequential ascending single IV dose of REGN4461 or matching placebo

Drug: REGN4461; Drug: Placebo

Part A: Single dose cohort 4

EXPERIMENTAL

Cohort 4 will receive a sequential ascending single SC dose of REGN4461 or matching placebo

Drug: REGN4461; Drug: Placebo

Part A: Single dose cohort 5

EXPERIMENTAL

Cohort 5 will receive a sequential ascending single IV dose of REGN4461 or matching placebo

Drug: REGN4461; Drug: Placebo

Part A: Single dose cohort 6

EXPERIMENTAL

Cohort 6 will receive a sequential ascending single SC dose of REGN4461 or matching placebo

Drug: REGN4461; Drug: Placebo

Part A: Single dose cohort 7

EXPERIMENTAL

Cohort 7 will receive a sequential ascending single IV dose of REGN4461 or matching placebo

Drug: REGN4461; Drug: Placebo

Part A: Single dose cohort 8

EXPERIMENTAL

Cohort 8 will receive a single IV dose of REGN4461 or matching placebo

Drug: REGN4461; Drug: Placebo

Part A: Single dose cohort 9

EXPERIMENTAL

Cohort 9 will receive a single IV dose of REGN4461 or matching placebo

Drug: REGN4461; Drug: Placebo

Part B: Repeated dose cohort 10

EXPERIMENTAL

Cohort 10 will receive repeated IV or SC doses of REGN4461 or matching placebo

Drug: REGN4461; Drug: Placebo

Interventions

REGN4461 DRUG

REGN4461

Part A: Single dose cohort 1; Part A: Single dose cohort 2; Part A: Single dose cohort 3; Part A: Single dose cohort 4; Part A: Single dose cohort 5; Part A: Single dose cohort 6; Part A: Single dose cohort 7; Part A: Single dose cohort 8; Part A: Single dose cohort 9; Part B: Repeated dose cohort 10

Placebo DRUG

Placebo-matching REGN4461

Part A: Single dose cohort 1; Part A: Single dose cohort 2; Part A: Single dose cohort 3; Part A: Single dose cohort 4; Part A: Single dose cohort 5; Part A: Single dose cohort 6; Part A: Single dose cohort 7; Part A: Single dose cohort 8; Part A: Single dose cohort 9; Part B: Repeated dose cohort 10

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Hospitalization (ie, \>24 hours) for any reason within 60 days of the screening visit
• History of hypothalamic amenorrhea or lipodystrophy.
• Change in body weight of more than 5% over the past 3 months prior to screening.
• Previous history of bariatric procedures for obesity (eg, sleeve gastrectomy, gastric bypass, banding, etc).
• Procedures for weight reduction (eg, liposuction) or body contouring in the past 6 months.
• Treatment with medications for (over-the-counter \[OTC\] or prescribed) weight loss (eg, lorcaserin, phentermine/topiramate, naltrexone HCl/bupropion HCl, liraglutide) in the past 3 months.
• History of major psychiatric disorders, eating disorders (eg, bulimia, anorexia).
• Current cigarette smoker or former smoker (cigarettes or e-cigarettes) who stopped smoking within 3 months prior to screening.
• History of recreational drug (including marijuana) or alcohol abuse (\>2 drinks per day) within a year prior to the screening visit.

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (1)

Regeneron Investigational Site

Antwerp, Belgium

Location

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2018
• First Posted: May 21, 2018
• Study Start: April 24, 2018
• Primary Completion: January 27, 2020
• Study Completion: January 27, 2020
• Last Updated: March 9, 2020

Record last verified: 2019-11

Locations

BE (1)