Obesity
Conditions
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.
Interventions
Participants will receive JNJ-64565111 Dose Level 1 SC once -weekly until Week 26.
Participants will receive JNJ-64565111 Dose Level 2 SC once-weekly until Week 26.
Participants will receive JNJ-64565111 Dose Level 3 SC once-weekly until Week 26.
DRUGLiraglutide
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.
DRUGPlacebo
Participants will receive matching placebo SC once-weekly until Week 26.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Body Weight at Week 26 | Baseline, Week 26 | Percent change in body weight in kilograms (kg) from baseline to Week 26 was reported. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Up to Week 30 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Greater Than or Equal to (>=) 5 Percent (%) Body Weight Loss at Week 26 | Week 26 | Number of participants with \>= 5% body weight loss from baseline to Week 26 were reported. |
| Number of Participants With Greater Than or Equal to 10 % Body Weight Loss at Week 26 | Week 26 | Number of participants with \>= 10 % body weight loss from baseline to Week 26 were reported. |
| Change From Baseline in Body Weight at Week 26 | Baseline, Week 26 | Change from baseline in body weight at Week 26 was reported. |
Countries
Belgium, Canada, Poland, Sweden, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 474 participants were randomized out of which 444 participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Double Blind: Placebo Participants self-administered the matching placebo of JNJ-64565111 subcutaneously (SC) once-weekly throughout the 26-week treatment phase or until early discontinuation of study drug. | 60 |
| Double Blind: JNJ-64565111 5.0 mg Participants self-administered 5.0 milligram (mg) JNJ-64565111 SC once weekly throughout the 26-week treatment phase or until early discontinuation of study drug. | 59 |
| Double Blind: JNJ-64565111 7.4 mg Participants self-administered 7.4 mg JNJ-64565111 SC once-weekly throughout the 26-week treatment phase or until early discontinuation of study drug. | 118 |
| Double Blind: JNJ-64565111 10.0 mg Participants self-administered 10.0 mg JNJ-64565111 SC once-weekly throughout the 26-week treatment phase or until early discontinuation of study drug. | 118 |
| Open Label: Liraglutide 3.0 mg Participant self-administered liraglutide at a starting dose of 0.6 mg SC once-daily on Day 1, followed by dose titration up to 1.2, 1.8, 2.4, and 3.0 mg in Weeks 2, 3, 4, and 5 (with 0.6 mg weekly increment up to the full dosage of 3.0 mg by Week 5). Participants then continued the 3.0 mg once-daily dosage until Week 26 or until early drug discontinuation. | 119 |
| Total | 474 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 8 | 5 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 0 | 6 | 4 | 1 |
Baseline characteristics
| Characteristic | Open Label: Liraglutide 3.0 mg | Double Blind: Placebo | Double Blind: JNJ-64565111 5.0 mg | Double Blind: JNJ-64565111 7.4 mg | Double Blind: JNJ-64565111 10.0 mg | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 45.6 years STANDARD_DEVIATION 11.71 | 46.9 years STANDARD_DEVIATION 11.84 | 47.3 years STANDARD_DEVIATION 11.18 | 46.2 years STANDARD_DEVIATION 11.68 | 46.2 years STANDARD_DEVIATION 12.16 | 46.3 years STANDARD_DEVIATION 11.73 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 3 Participants | 5 Participants | 9 Participants | 11 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 105 Participants | 57 Participants | 54 Participants | 108 Participants | 107 Participants | 431 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 8 Participants | 3 Participants | 8 Participants | 8 Participants | 34 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 105 Participants | 51 Participants | 56 Participants | 106 Participants | 103 Participants | 421 Participants |
| Region of Enrollment BELGIUM | 18 Participants | 7 Participants | 5 Participants | 15 Participants | 13 Participants | 58 Participants |
| Region of Enrollment CANADA | 16 Participants | 9 Participants | 8 Participants | 12 Participants | 17 Participants | 62 Participants |
| Region of Enrollment POLAND | 15 Participants | 8 Participants | 6 Participants | 14 Participants | 18 Participants | 61 Participants |
| Region of Enrollment SWEDEN | 14 Participants | 12 Participants | 14 Participants | 22 Participants | 19 Participants | 81 Participants |
| Region of Enrollment UNITED KINGDOM | 17 Participants | 5 Participants | 8 Participants | 17 Participants | 11 Participants | 58 Participants |
| Region of Enrollment UNITED STATES | 39 Participants | 19 Participants | 18 Participants | 38 Participants | 40 Participants | 154 Participants |
| Sex: Female, Male Female | 89 Participants | 48 Participants | 47 Participants | 86 Participants | 86 Participants | 356 Participants |
| Sex: Female, Male Male | 30 Participants | 12 Participants | 12 Participants | 32 Participants | 32 Participants | 118 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 59 | 0 / 118 | 0 / 118 | 1 / 119 |
| other Total, other adverse events | 33 / 60 | 43 / 59 | 106 / 118 | 104 / 118 | 81 / 119 |
| serious Total, serious adverse events | 4 / 60 | 3 / 59 | 2 / 118 | 4 / 118 | 4 / 119 |
Outcome results
Primary
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.
Time frame: Up to Week 30
Population: Safety analysis set included all randomized participants who had received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double Blind: Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 43 Participants |
| Double Blind: JNJ-64565111 5.0 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 53 Participants |
| Double Blind: JNJ-64565111 7.4 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 110 Participants |
| Double Blind: JNJ-64565111 10.0 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 110 Participants |
| Open Label: Liraglutide 3.0 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 96 Participants |
Primary
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.
Time frame: Baseline, Week 26
Population: Modified intent-to-treat (mITT) population included all ITT participants who had taken at least 1 dose of study drug and had at least 1 post-baseline body weight measurement; for liraglutide, only those who titrated to 3.0 mg were included in mITT population. N (number of participants analyzed) = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Double Blind: Placebo | Percent Change From Baseline in Body Weight at Week 26 | -1.76 Percent Change | Standard Error 0.73 |
| Double Blind: JNJ-64565111 5.0 mg | Percent Change From Baseline in Body Weight at Week 26 | -8.51 Percent Change | Standard Error 0.76 |
| Double Blind: JNJ-64565111 7.4 mg | Percent Change From Baseline in Body Weight at Week 26 | -9.83 Percent Change | Standard Error 0.56 |
| Double Blind: JNJ-64565111 10.0 mg | Percent Change From Baseline in Body Weight at Week 26 | -11.80 Percent Change | Standard Error 0.58 |
| Open Label: Liraglutide 3.0 mg | Percent Change From Baseline in Body Weight at Week 26 | -7.54 Percent Change | Standard Error 0.54 |
p-value: <0.00195% CI: [-9.31, -4.19]Dunnett's method
p-value: <0.00195% CI: [-10.31, -5.84]Dunnett's method
p-value: <0.00195% CI: [-12.31, -7.78]Dunnett's method
p-value: <0.00195% CI: [-7.99, -3.57]Dunnett's method
Secondary
Change From Baseline in Body Weight at Week 26
Change from baseline in body weight at Week 26 was reported.
Time frame: Baseline, Week 26
Population: mITT population included all ITT participants who had taken at least 1 dose of study drug and had at least 1 post-baseline body weight measurement; for liraglutide, only those who titrated to 3.0 mg were included in mITT population. N (number of participants analyzed) = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Double Blind: Placebo | Change From Baseline in Body Weight at Week 26 | -2.05 kg | Standard Error 0.827 |
| Double Blind: JNJ-64565111 5.0 mg | Change From Baseline in Body Weight at Week 26 | -9.58 kg | Standard Error 0.861 |
| Double Blind: JNJ-64565111 7.4 mg | Change From Baseline in Body Weight at Week 26 | -11.07 kg | Standard Error 0.633 |
| Double Blind: JNJ-64565111 10.0 mg | Change From Baseline in Body Weight at Week 26 | -13.23 kg | Standard Error 0.656 |
| Open Label: Liraglutide 3.0 mg | Change From Baseline in Body Weight at Week 26 | -8.32 kg | Standard Error 0.61 |
Secondary
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.
Time frame: Week 26
Population: mITT population included all ITT participants who had taken at least 1 dose of study drug and had at least 1 post-baseline body weight measurement; for liraglutide, only those who titrated to 3.0 mg were included in mITT population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double Blind: Placebo | Number of Participants With Greater Than or Equal to 10 % Body Weight Loss at Week 26 | 2 Participants |
| Double Blind: JNJ-64565111 5.0 mg | Number of Participants With Greater Than or Equal to 10 % Body Weight Loss at Week 26 | 23 Participants |
| Double Blind: JNJ-64565111 7.4 mg | Number of Participants With Greater Than or Equal to 10 % Body Weight Loss at Week 26 | 43 Participants |
| Double Blind: JNJ-64565111 10.0 mg | Number of Participants With Greater Than or Equal to 10 % Body Weight Loss at Week 26 | 46 Participants |
| Open Label: Liraglutide 3.0 mg | Number of Participants With Greater Than or Equal to 10 % Body Weight Loss at Week 26 | 27 Participants |
Secondary
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.
Time frame: Week 26
Population: mITT population included all ITT participants who had taken at least 1 dose of study drug and had at least 1 post-baseline body weight measurement; for liraglutide, only those who titrated to 3.0 mg were included in mITT population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double Blind: Placebo | Number of Participants With Greater Than or Equal to (>=) 5 Percent (%) Body Weight Loss at Week 26 | 8 Participants |
| Double Blind: JNJ-64565111 5.0 mg | Number of Participants With Greater Than or Equal to (>=) 5 Percent (%) Body Weight Loss at Week 26 | 34 Participants |
| Double Blind: JNJ-64565111 7.4 mg | Number of Participants With Greater Than or Equal to (>=) 5 Percent (%) Body Weight Loss at Week 26 | 70 Participants |
| Double Blind: JNJ-64565111 10.0 mg | Number of Participants With Greater Than or Equal to (>=) 5 Percent (%) Body Weight Loss at Week 26 | 62 Participants |
| Open Label: Liraglutide 3.0 mg | Number of Participants With Greater Than or Equal to (>=) 5 Percent (%) Body Weight Loss at Week 26 | 56 Participants |