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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03530514
• Date of registration: 07/05/2018
• Prospective Registration: No
• Primary sponsor: Regeneron Pharmaceuticals
• Public title: A Study to Examine the Safety, Tolerability and Biological Effects of REGN4461 in Healthy Volunteers
• Scientific title: A Phase 1 Randomized, Double-Blind, Placebo-Controlled, 2-Part Study to Assess the Safety and Tolerability, Pharmacokinetics, And Pharmacodynamics of Single and Multiple Doses of REGN4461 in Healthy Subjects
• Date of first enrolment: April 24, 2018
• Target sample size: 113
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03530514
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Basic Science. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 1

Countries of recruitment

Belgium

Contacts

• Name: Clinical Trial Management
• Affiliation: Regeneron Pharmaceuticals

Key inclusion & exclusion 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 Exclusion Criteria (Parts A and B):

- 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.

- History of hepatitis B infection or a positive hepatitis B surface antigen (HbsAg+) at
screening

- History of HIV infection or HIV seropositive at the screening visit.

- History of hepatitis C infection or positive hepatitis C antibody test result at
screening.

- Pregnant or breastfeeding women.

Note: Other inclusion/ exclusion criteria apply



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Healthy Volunteers

Intervention(s)

Drug: REGN4461

Drug: Placebo

Primary Outcome(s)

Number of treatment-emergent adverse events (TEAEs) [Time Frame: Up to week 27]

Secondary Outcome(s)

Absolute change from baseline to week 12 in body weight in overweight or obese participants [Time Frame: Baseline to week 12]

Change in lipid-regulating protein levels over time after repeated doses of REGN4461 [Time Frame: Up to week 27]

Incidence of anti-drug antibodies to REGN4461 over time after repeated doses of REGN4461 [Time Frame: Up to week 27]

PK parameter: time to Cmax (tmax) [Time Frame: Up to week 27]

Concentrations of REGN4461 in serum over time [Time Frame: Up to week 27]

Change from baseline in caloric intake in response to standardized meals in overweight or obese participants [Time Frame: Baseline to week 12]

Incidence of anti-drug antibodies to REGN4461 over time after single doses of REGN4461 [Time Frame: Up to week 16]

PK parameter: peak concentration (Cmax) [Time Frame: Up to week 27]

Change in lipid-regulating protein levels over time after single doses of REGN4461 [Time Frame: Up to week 16]

Percent change from baseline to week 12 in body weight in overweight or obese participants [Time Frame: Baseline to week 12]

Pharmacokinetic (PK) parameter: Area under curve (AUC) computed from time zero to the time of the last positive concentration (AUClast) [Time Frame: Up to week 27]

PK parameter: AUC computed across a dosing interval with length t (AUCo-t) [Time Frame: Upt to week 27]

PK parameter: clearance (CL) [Time Frame: Up to week 27]

PK parameter: trough concentration (Ctrough) [Time Frame: Up to week 27]

Secondary ID(s)

R4461-HV-1794

2018-000327-14

Source(s) of Monetary Support

Please refer to primary and secondary sponsors