A Study to Evaluate the Safety and Efficacy of JNJ-64565111 in Non-diabetic Severely Obese Participants

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the effects of JNJ-64565111 compared with placebo after 26 weeks of treatment on the percent change in body weight from baseline and to assess the safety and tolerability, in non-diabetic severely obese participants.

Official Title
-----------------
A Randomized, Double-blind Placebo-controlled and Open-label Active-controlled, Parallel-group, Multicenter, Dose-ranging Study to Evaluate the Safety and Efficacy of JNJ-64565111 in Non-diabetic Severely Obese Subjects

Conditions
-----------------
Obesity

Intervention / Treatment
-----------------
* Drug: JNJ-64565111 Dose Level 1
* Drug: JNJ-64565111 Dose Level 2
* Drug: JNJ-64565111 Dose Level 3
* Drug: Liraglutide
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Body mass index (BMI) greater than or equal to (>=) 35 to less than or equal to (<=) 50 kilogram per square meter (kg/m^2) at the screening visit Stable weight (that is, change of <= 5 percent [%] within 12 weeks before screening based on medical history) Women must be either: (a) Postmenopausal, or (b) Permanently sterilized or otherwise be incapable of pregnancy, or (c) Heterosexually active and practicing a highly effective method of birth control, or (d) Not heterosexually active Woman of childbearing potential have a negative pregnancy test at screening Willing and able to adhere to specific the prohibitions and restrictions Exclusion Criteria: History of obesity with a known secondary cause (for example, Cushing's disease/syndrome) History of Type 1 diabetes mellitus, Type 2 diabetes mellitus (T2DM), diabetic ketoacidosis (DKA), pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy Has a Hemoglobin A1c (HbA1c) of >= 6.5% or fasting plasma glucose (FPG) >= 126 milligrams per deciliter (mg/dL) (>= 7.0 millimoles per liter [mmol/L]) at screening Screening calcitonin of >= 50 picograms per milliliter (pg/mL) personal history or family history of medullary thyroid cancer, or of multiple endocrine neoplasia syndrome type 2 (MEN 2), regardless of time prior to screening History of glucagonoma

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Double-Blind: JNJ-64565111 Dose Level 1<br>Participants will receive a JNJ-64565111 Dose Level 1 subcutaneously (SC) once-weekly for 26-week treatment phase. | Drug: JNJ-64565111 Dose Level 1<br>* Participants will receive JNJ-64565111 Dose Level 1 SC once -weekly until Week 26.<br>|
| Experimental: Double-Blind: JNJ-64565111 Dose Level 2<br>Participants will receive a JNJ-64565111 Dose Level 2 SC once-weekly for 26-week treatment phase. | Drug: JNJ-64565111 Dose Level 2<br>* Participants will receive JNJ-64565111 Dose Level 2 SC once-weekly until Week 26.<br>|
| Experimental: Double-Blind: JNJ-64565111 Dose Level 3<br>Participants will receive a JNJ-64565111 Dose Level 3 SC once-weekly for 26-week treatment phase. | Drug: JNJ-64565111 Dose Level 3<br>* Participants will receive JNJ-64565111 Dose Level 3 SC once-weekly until Week 26.<br>|
| Placebo Comparator: Double-Blind: Placebo<br>Participants will receive placebo matching to JNJ-64565111 SC once-weekly for 26-week treatment phase. | Drug: Placebo<br>* Participants will receive matching placebo SC once-weekly until Week 26.<br>|
| Active Comparator: Open-Label: 3.0 milligram (mg) Liraglutide<br>Participant will receive once-daily doses of 0.6, 1.2, 1.8, 2.4, or 3.0 mg. The participants will receive liraglutide at a starting dose of 0.6 mg SC once-daily on Day 1. Participants will be instructed to increase the dose of liraglutide by 0.6 mg dose increment every 7 days, up to the full dosage of 3.0 mg by Week 5. Participants will then continue on the 3.0 mg once-daily dosage until Week 26. | Drug: Liraglutide<br>* Participants will receive liraglutide at a starting dose of 0.6 mg then dose will be ramped up by 0.6 mg daily until reaching 3.0 mg. Participants will then continue on the 3.0 mg once-daily dosage until Week 26.<br>* Other names: Saxenda;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Body Weight at Week 26 | Percent change in body weight in kilograms (kg) from baseline to Week 26 was reported. | Baseline, Week 26 | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. A TEAE was defined as an AE with an onset after the initiation study drug and before the last study drug date of the double-blind (26-week) treatment phase for plus 28 days for liraglutide participants, and plus 35 days for JNJ-64565111 and placebo participants. | Up to Week 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Greater Than or Equal to (>=) 5 Percent (%) Body Weight Loss at Week 26 | Number of participants with >= 5% body weight loss from baseline to Week 26 were reported. | Week 26 | 
| Number of Participants With Greater Than or Equal to 10 % Body Weight Loss at Week 26 | Number of participants with >= 10 % body weight loss from baseline to Week 26 were reported. | Week 26 | 
| Change From Baseline in Body Weight at Week 26 | Change from baseline in body weight at Week 26 was reported. | Baseline, Week 26 |