Clinical trial NCT03625778: A Study to Assess Safety, Tolerability, and Pharmacokinetics of MEDI0382 in Non-diabetic Obese Participants
Official title: A Randomized, Blinded, Placebo-controlled Study to Assess Pharmacokinetics, Safety, and Tolerability of Ascending Doses of MEDI0382 in Non-diabetic Obese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Obesity
Keywords: Obesity
MEDI0382
Overweight
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2018-08-10
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1, randomized, blinded, placebo-controlled study in up to approximately 51 non-diabetic obese participants with a body mass index (BMI) ≥ 35 kg/m\^2. The participants will be observed among 3 separate cohorts and participate in the study for up to approximately 27 weeks, including a screening period (including a run-in), treatment period, and safety follow-up.

Detailed description: This is a Phase 1, randomized, blinded, placebo-controlled study in up to approximately 51 non-diabetic obese participants with a BMI ≥ 35 kg/m2. Participants will be blinded, but investigators/site staff and sponsor will be unblinded for Cohort 1. In Cohorts 2 and 3 participants, investigators, and contract research organization personnel are blinded to investigational product and sponsor is unblinded. The participants will participate in the study for up to approximately 27 weeks, including a screening period (including a run-in), treatment period, and safety follow-up.

Participants will be randomized 4:1 to MEDI0382 (n=12) or placebo (n=3) for Cohort 1 and randomized 2:1 to MEDI0382 (n=12) or placebo (n=6) for Cohorts 2 and 3. In Cohort 1 participants randomized to MEDI0382 or placebo will be dosed daily with a weekly titration schedule until the highest clinically tolerated dose (CTD) is established. In Cohort 2 participants randomized to MEDI0382 or placebo will be dosed daily with a 2 week titration schedule up to the highest CTD is established in Cohort 1. In Cohort 3 participants randomized to MEDI0382 or placebo will be dosed daily with a 4 week participants schedule up to the highest CTD established in Cohort 1. Once the highest CTD is identified, participants will continue on the highest CTD for an additional 2 weeks of treatment for Cohort 1 and 3 and additional 4 weeks treatment for Cohort 2. All participants will return 28 days post last dose for a safety follow-up visit.

Eligibility criteria: Key Inclusion Criteria:

1. Provision of written informed consent
2. Male and female participants age 18 through 65 years
3. BMI ≥ 35 kg/m\^2
4. Hemoglobin A1c level of \< 6.5%
5. Female participants must have a negative pregnancy test and must not be lactating.
6. Females of childbearing potential using appropriate birth control to avoid pregnancy during the study.
7. Stable body weight
8. Willing and able to adhere to the visit/protocol schedule, including following lifestyle advice with respect to diet and exercise for the duration of the study
9. Willing and able to self-administer daily SC injections following an initial self-injection training

Key Exclusion Criteria:

1. Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks prior to Study Day 1 dosing.
2. Any condition that, in the opinion of the investigator, would interfere with the evaluation of the investigational product or interpretation of participants safety or study results.
3. Active participation in any other investigation clinical study.
4. Any prescription or non-prescription drugs for weight loss including herbal or other dietary supplements used within the past 3 months prior to screening.
5. Previous glucagon-like peptide-1 (GLP-1) use within 3 months prior to screening.
6. Any positive results for serum hepatitis B surface antigen, hepatitis C virus antibody and/or human immunodeficiency virus (HIV) antibody at screening.
7. Laboratory tests results as specified in the protocol (laboratory tests may be repeated once for confirmation of out of range values at screening).
8. Significant hepatic or renal impairment
9. Poorly controlled hypertension
10. Known or suspected history of drug or alcohol abuse within the past year or positive current test
11. Previous surgical procedures for weight loss

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) for Cohorts 1, 2, and 3
timeFrame: From Day 1 through 28 days after the last dose of study drug (approximately 13, 18, and 22 weeks for Cohorts 1, 2, and 3, respectively)
measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs for Cohorts 1, 2, and 3
timeFrame: From Day 1 through 28 days after the last dose of study drug (approximately 13, 18, and 22 weeks for Cohorts 1, 2, and 3, respectively)
measure: Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs for Cohorts 1, 2, and 3
timeFrame: From Day 1 through 28 days after the last dose of study drug (approximately 13, 18, and 22 weeks for Cohorts 1, 2, and 3, respectively)
measure: Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs for Cohorts 1, 2, and 3
timeFrame: From Day 1 through 28 days after the last dose of study drug (approximately 13, 18, and 22 weeks for Cohorts 1, 2, and 3, respectively)
measure: Change in Blood Pressure from Baseline to End of Dosing as Measured by Telemetry for Cohort 1
timeFrame: From Baseline (Day -1) through end of dosing (Day 63)
measure: Change in Respiratory Rate from Baseline to End of Dosing as Measured by Telemetry for Cohort 1
timeFrame: From Baseline (Day -1) through end of dosing (Day 63)
measure: Change in Pulse Rate from Baseline to End of Dosing as Measured by Telemetry for Cohort 1
timeFrame: From Baseline (Day -1) through end of dosing (Day 63)
measure: Change in Temperature from Baseline to End of Dosing as Measured by Telemetry for Cohort 1
timeFrame: From Baseline (Day -1) through end of dosing ( Day 63)
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of MEDI0382 for Cohort 1
timeFrame: Predose (-5 minutes) and 1, 2, 4, 6, 8, 12, and 24 hours postdose on Days 7, 14, 21, 28, 35, 42, and 49 for MEDI0382 Doses 1 to 7, respectively
measure: Cmax of MEDI0382 Dose 1 on Day 1 for Cohort 1
timeFrame: Predose (-5 minutes) and 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1
measure: Area Under the Concentration-time Curve at the end of the Dosing interval (AUCτ) of MEDI0382 for Cohort 1
timeFrame: Predose (-5 minutes) and 1, 2, 4, 6, 8, 12, and 24 hours postdose on Days 7, 14, 21, 28, 35, 42, and 49 for MEDI0382 Doses 1 to 7, respectively
measure: AUCτ of MEDI0382 Dose 1 on Day 1 for Cohort 1
timeFrame: Predose (-5 minutes) and 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1
measure: Time to Maximum Observed Plasma Concentration (Tmax) of MEDI0382 for Cohort 1
timeFrame: Predose (-5 minutes) and 1, 2, 4, 6, 8, 12, and 24 hours postdose on Days 7, 14, 21, 28, 35, 42, and 49 for MEDI0382 Doses 1 to 7, respectively
measure: Tmax of MEDI0382 Dose 1 on Day 1 for Cohort 1
timeFrame: Predose (-5 minutes) and 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1
measure: Plasma Concentration of MEDI0382 for Cohorts 2 and 3
timeFrame: Cohort 2: predose and 6 hours postdose on Days 1, 15, 29, 43, and 57 for MEDI0382 Doses 1, 2, 3, 5, and 7, respectively; Cohort 3: predose and 6 hours postdose on Days 1, 29, 57, and 85 for MEDI0382 Doses 1, 8, 4, and 7, respectively
measure: Plasma Concentration of MEDI0382 Dose 7 on Day 71 for Cohort 2 and MEDI0382 Dose 7 on Day 113 for Cohort 3
timeFrame: Cohort 2: predose and 6 hours postdose on Day 71 for MEDI0382 Dose 7; Cohort 3: predose and 6 hours postdose on Day 113 for MEDI0382 Dose 7
measure: Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI0382 in all Cohorts
timeFrame: Predose on Baseline (Day -1) and follow-up visit (28 days after the last dose) for each cohort; predose on Days 28 and 50 for Cohort 1, on Days 7, 28, 71, 98 for Cohort 2, and on Days 7, 28, 71, 126 for Cohort 3
Other outcomes:
Locations:
city: Daytona Beach
country: United States
facility: Research Site
state: Florida
city: Dallas
country: United States
facility: Research Site
state: Texas
Study officials:
References: