Obesity
Conditions
Keywords
Type 2 diabetes mellitus, weight loss
Brief summary
This was a multi-center, randomized, placebo-controlled, participant-and-investigator-blinded, sponsor open-label study in obese participants with or without Type 2 Diabetes Mellitus.
Detailed description
The study comprised a screening/baseline period of up to 35 days (5 weeks), a 14-week treatment period in which participants were administered MBL949 or placebo at 8 biweekly intervals starting on Day 1 and a 10-week follow-up period. Participants were to be enrolled to: * MBL949 Arm 1, MBL949 Arm 2 and placebo in a 1:1:1 ratio * MBL949 Arm 3, MBL949 Arm 4 and placebo in a 1:1:1 ratio * If MBL949 Arm 1 was tolerated, MBL949 Arm 5 was enrolled with a 2:1 ratio (MBL:placebo) within each stratum.
Interventions
DRUGMBL949
subcutaneous injections administered for 14 weeks
DRUGPlacebo
Placebo Comparator to MLB949
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Body mass index: ≥ 32 kg/m2, weight ≥ 77 kg, stable body weight i.e., less than 1.5 kg self-reported change within 90 days * Diagnosed T2DM as documented by medical history and confirmed by Investigator and with diagnosed duration \< 10 yrs, HbA1c ≤ 9%, and fasting C-peptide ≥ 0.2 ng/ml * If treated for T2DM, treatment must be limited to diet and exercise and treatment with one of the following anti-diabetic agents (stable for 90 days prior to randomization): * Metformin * SGLT2i inhibitors (if prescribed as the first line, ie. single agent) * DDP4 inhibitors * Acarbose
Exclusion criteria
* Vitals at screening: * systolic blood pressure less than 95 mm Hg or greater than 155 mm Hg * diastolic blood pressure less than 60 mg Hg or greater than 95 mm Hg * pulse rate less than 56 or greater than 110 bpm * History of bariatric surgery, Roux-en-Y Gastric Bypass, Sleeve Gastrectomy, gastric banding, and any other intrabdominal procedures designed for weight loss at screening * History of myocardial infarction with 2 years of screening * Diet attempts within 90 days before screening * Participation in organized weight reduction program within 6 months of screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and Severity of Adverse Events | Baseline to Day 169 | Number of participants with adverse events reported after the first dose of study medication or events present prior to treatment but increase in severity |
| Change-from-baseline in Weight | Week 16 | Baseline weight is defined as the last weight measurement before dosing in kilograms |
Countries
United States
Participant flow
Recruitment details
A total of 4 research centers in United States participated in the study.
Pre-assignment details
Participants underwent a screening visit between Day -35 and Day -15 to determine their eligibility for the study. On Day 1, participants went to the clinic after an overnight fast of at least 10 hours to complete the Day 1 assessments prior to dosing.
Participants by arm
| Arm | Count |
|---|---|
| MBL949 Arm 1 MBL949 one 3 mg dose followed by two doses of 6 mg followed by five doses of 4.5 mg | 14 |
| MBL949 Arm 2 MBL949 two 3 mg doses followed by six doses of 4.5 mg | 22 |
| MBL949 Arm 3 MBL949 one 12 mg dose followed by seven doses of 4.5 mg | 16 |
| MBL949 Arm 4 MBL949 one 1.5 mg dose followed by seven doses of 2.2 mg | 15 |
| MBL949 Arm 5 MBL949 one 3 mg dose followed by two doses of 6 mg followed by five doses of 7.5 mg | 15 |
| Placebo Placebo to MBL949 | 44 |
| Total | 126 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 4 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 | 4 | 0 | 5 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Study terminated by sponsor | 0 | 6 | 0 | 0 | 0 | 5 |
| Overall Study | Subject decision | 0 | 4 | 0 | 2 | 5 | 2 |
Baseline characteristics
| Characteristic | MBL949 Arm 1 | MBL949 Arm 2 | MBL949 Arm 3 | MBL949 Arm 4 | MBL949 Arm 5 | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 47.4 years STANDARD_DEVIATION 9.53 | 45.8 years STANDARD_DEVIATION 7.77 | 44.8 years STANDARD_DEVIATION 11.23 | 45.8 years STANDARD_DEVIATION 8.98 | 41.6 years STANDARD_DEVIATION 10.68 | 44.0 years STANDARD_DEVIATION 10.09 | 44.7 years STANDARD_DEVIATION 9.7 |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 4 Participants | 2 Participants | 6 Participants | 3 Participants | 11 Participants | 29 Participants |
| Race/Ethnicity, Customized White | 11 Participants | 18 Participants | 14 Participants | 9 Participants | 12 Participants | 33 Participants | 97 Participants |
| Sex: Female, Male Female | 8 Participants | 17 Participants | 13 Participants | 12 Participants | 13 Participants | 38 Participants | 101 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 3 Participants | 3 Participants | 2 Participants | 6 Participants | 25 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 22 | 0 / 16 | 0 / 15 | 0 / 15 | 0 / 82 | 0 / 44 | 0 / 126 |
| other Total, other adverse events | 11 / 14 | 20 / 22 | 15 / 16 | 10 / 15 | 14 / 15 | 70 / 82 | 26 / 44 | 96 / 126 |
| serious Total, serious adverse events | 0 / 14 | 0 / 22 | 0 / 16 | 0 / 15 | 0 / 15 | 0 / 82 | 0 / 44 | 0 / 126 |
Outcome results
Primary
Change-from-baseline in Weight
Baseline weight is defined as the last weight measurement before dosing in kilograms
Time frame: Week 16
Population: PD analysis set: included all subjects who received any study drug, had Pharmacodynamics (PD) data, and had no protocol deviations with relevant impact on PD data. Only participants with weight data at Baseline and Week 16 were included in the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MBL949 Arm 1 | Change-from-baseline in Weight | -2.6 kg |
| MBL949 Arm 2 | Change-from-baseline in Weight | -2.0 kg |
| MBL949 Arm 3 | Change-from-baseline in Weight | -2.0 kg |
| MBL949 Arm 4 | Change-from-baseline in Weight | -0.1 kg |
| MBL949 Arm 5 | Change-from-baseline in Weight | 0.3 kg |
| Pooled MBL949 | Change-from-baseline in Weight | -1.4 kg |
| Placebo | Change-from-baseline in Weight | -0.7 kg |
Comparison: Comparison of adjusted meansp-value: 0.018280% CI: [-2.9, -0.9]MMRM analysis
p-value: 0.120580% CI: [-2.4, -0.2]MMRM analysis
p-value: 0.093180% CI: [-2.2, -0.3]MMRM analysis
p-value: 0.499480% CI: [-0.5, 1.7]MMRM analysis
p-value: 0.229580% CI: [-0.1, 2.1]MMRM analysis
p-value: 0.211480% CI: [-1.3, 0]MMRM analysis
Primary
Frequency and Severity of Adverse Events
Number of participants with adverse events reported after the first dose of study medication or events present prior to treatment but increase in severity
Time frame: Baseline to Day 169
Population: Safety Set: included all subjects that received any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MBL949 Arm 1 | Frequency and Severity of Adverse Events | Serious AEs | 0 Participants |
| MBL949 Arm 1 | Frequency and Severity of Adverse Events | AEs of mild intensity | 10 Participants |
| MBL949 Arm 1 | Frequency and Severity of Adverse Events | AEs of severe intensity | 0 Participants |
| MBL949 Arm 1 | Frequency and Severity of Adverse Events | Total AEs | 11 Participants |
| MBL949 Arm 1 | Frequency and Severity of Adverse Events | AEs of moderate intensity | 4 Participants |
| MBL949 Arm 1 | Frequency and Severity of Adverse Events | Study drug-related AEs | 9 Participants |
| MBL949 Arm 2 | Frequency and Severity of Adverse Events | Total AEs | 20 Participants |
| MBL949 Arm 2 | Frequency and Severity of Adverse Events | AEs of severe intensity | 2 Participants |
| MBL949 Arm 2 | Frequency and Severity of Adverse Events | Serious AEs | 0 Participants |
| MBL949 Arm 2 | Frequency and Severity of Adverse Events | AEs of mild intensity | 19 Participants |
| MBL949 Arm 2 | Frequency and Severity of Adverse Events | Study drug-related AEs | 18 Participants |
| MBL949 Arm 2 | Frequency and Severity of Adverse Events | AEs of moderate intensity | 8 Participants |
| MBL949 Arm 3 | Frequency and Severity of Adverse Events | Study drug-related AEs | 15 Participants |
| MBL949 Arm 3 | Frequency and Severity of Adverse Events | AEs of moderate intensity | 7 Participants |
| MBL949 Arm 3 | Frequency and Severity of Adverse Events | Serious AEs | 0 Participants |
| MBL949 Arm 3 | Frequency and Severity of Adverse Events | AEs of severe intensity | 0 Participants |
| MBL949 Arm 3 | Frequency and Severity of Adverse Events | Total AEs | 15 Participants |
| MBL949 Arm 3 | Frequency and Severity of Adverse Events | AEs of mild intensity | 15 Participants |
| MBL949 Arm 4 | Frequency and Severity of Adverse Events | Study drug-related AEs | 8 Participants |
| MBL949 Arm 4 | Frequency and Severity of Adverse Events | Total AEs | 10 Participants |
| MBL949 Arm 4 | Frequency and Severity of Adverse Events | AEs of mild intensity | 10 Participants |
| MBL949 Arm 4 | Frequency and Severity of Adverse Events | AEs of moderate intensity | 3 Participants |
| MBL949 Arm 4 | Frequency and Severity of Adverse Events | AEs of severe intensity | 1 Participants |
| MBL949 Arm 4 | Frequency and Severity of Adverse Events | Serious AEs | 0 Participants |
| MBL949 Arm 5 | Frequency and Severity of Adverse Events | AEs of severe intensity | 0 Participants |
| MBL949 Arm 5 | Frequency and Severity of Adverse Events | AEs of mild intensity | 14 Participants |
| MBL949 Arm 5 | Frequency and Severity of Adverse Events | Study drug-related AEs | 12 Participants |
| MBL949 Arm 5 | Frequency and Severity of Adverse Events | Serious AEs | 0 Participants |
| MBL949 Arm 5 | Frequency and Severity of Adverse Events | AEs of moderate intensity | 8 Participants |
| MBL949 Arm 5 | Frequency and Severity of Adverse Events | Total AEs | 14 Participants |
| Pooled MBL949 | Frequency and Severity of Adverse Events | AEs of moderate intensity | 30 Participants |
| Pooled MBL949 | Frequency and Severity of Adverse Events | AEs of severe intensity | 3 Participants |
| Pooled MBL949 | Frequency and Severity of Adverse Events | AEs of mild intensity | 68 Participants |
| Pooled MBL949 | Frequency and Severity of Adverse Events | Study drug-related AEs | 62 Participants |
| Pooled MBL949 | Frequency and Severity of Adverse Events | Total AEs | 70 Participants |
| Pooled MBL949 | Frequency and Severity of Adverse Events | Serious AEs | 0 Participants |
| Placebo | Frequency and Severity of Adverse Events | AEs of moderate intensity | 7 Participants |
| Placebo | Frequency and Severity of Adverse Events | AEs of mild intensity | 29 Participants |
| Placebo | Frequency and Severity of Adverse Events | Serious AEs | 0 Participants |
| Placebo | Frequency and Severity of Adverse Events | AEs of severe intensity | 2 Participants |
| Placebo | Frequency and Severity of Adverse Events | Study drug-related AEs | 19 Participants |
| Placebo | Frequency and Severity of Adverse Events | Total AEs | 30 Participants |