Clinical trial NCT03005288: Safety, Pharmacokinetics and Efficacy of Bimagrumab in Overweight and Obese Patients With Type 2 Diabetes
Official title: A Randomized, Subject- and Investigator-blinded, Placebo Controlled Study to Assess the Safety, Pharmacokinetics and Efficacy of Intravenous Bimagrumab in Overweight and Obese Patients With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Keywords: type 2 diabetes
obesity
DXA
MRI
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-12-29
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study assessed the safety, pharmacokinetics and efficacy of bimagrumab when administered in overweight and obese patients with type 2 diabetes

Detailed description: A non-confirmatory, randomized, subject and investigator blinded, placebo controlled, parallel-arm study, investigating a 48-week treatment period with i.v. bimagrumab 10 mg/kg in overweight and obese subjects with type 2 diabetes.

Participants were randomized and assigned to one of the following 2 treatment arms in a ratio of 1:1:

Arm 1: Bimagrumab 10 mg/kg up to maximum 1200 mg, every 4 weeks (12 doses) until week 44.

Arm 2: Placebo, every 4 weeks (12 doses) until week 44.

The study consisted of a screening baseline period of 3 weeks, treatment period of 48 weeks and then a follow-up period of 8 weeks.

Treatment period visits were scheduled every 4 weeks until week 44. Administration of bimagrumab or placebo was done via an i.v. infusion over 30 minutes followed by flushing for 15 minutes. Subjects were asked to return to the Investigator site for dosing approximately every 4 weeks during the treatment period. During those visits, subjects were evaluated for safety, tolerability, PK and efficacy. The treatment period ended approximately 4 weeks after the last dose administration.

Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes with HbA1c between 6.5% and 10% at screening with stable treatment for 3 months prior to randomization
* On one of the following anti-diabetes regimens with stable treatment for approximately 3 months prior to randomization: 1) metformin monotherapy; 2) DPP4 inhibitor agent monotherapy; 3) combination therapy of metformin and DPP4 inhibitor agent; 4) no anti-diabetes therapy.
* Body Mass Index of 28 to 40 kg/m2 at screening
* Body weight between 65 and 140 kg at screening

Exclusion Criteria:

* Women of child-bearing potential unless they are using highly effective methods of contraception
* Diabetes other than Type 2 such as Type 1 diabetes, surgically induced diabetes, "brittle" type 2 diabetes as per investigator judgement, history of severe hypoglycemic episodes in the year preceding screening or hypoglycemic unawareness
* History of clinically significant arrythmias, heart failure, unstable angina, myocardial infarction or stroke, coronary artery bypass graft surgery, or percutaneous coronary intervention, deep vein thrombosis/pulmonary embolism, valve disorders or defects, pulmonary hypertension within 6 months of screening or 1 year for drug-eluting stents
* Tachycardia
* Use of anti-obesity medications, nutritional supplements or over the counter products for weight loss within 3 months of screening
* Use of medications known to induce weight gain such as some anti-convulsant and psychotropic medications within 3 months of screening
* Any chronic active infection (e.g., HIV, Hepatitis B or C, tuberculosis, etc) or has received anti-HCV treatments within the previous 6 months.
* Uncontrolled thyroid disease. Stable euthyroid patients on stable thyroid replacement therapy for at least 3 months of screening are allowed.
* Abnormal liver function tests such as SGOT, SGPT, alkaline phosphatase, or serum bilirubin, or abnormal lipase and/or amylase.
* Known history or presence of severe active acute or chronic liver disease (e.g., cirrhosis).
* Uncontrolled depression
* Use of skeletal muscle anabolic agents in any form for 3 months prior to screening
* Chronic kidney disease \[estimated glomerular filtration rate (GFR) \< 30 mL/min\];

Primary outcomes:
measure: Change From Baseline in Total Body Fat Mass by Dual Energy X-ray Absorptiometry (DXA) at Week 48
timeFrame: Baseline, Week 48
Secondary outcomes:
measure: Change From Baseline in Total Body Fat Mass by Dual Energy X-ray Absorptiometry (DXA) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in HbA1c at Week 24 and 48
timeFrame: Baseline, Week 24, Week 48
measure: The Trough Observed Analyte Concentration (Ctrough) of Repeat Doses of BYM338 10 mg/kg on Day 84, 168, 252, 308 and 336
timeFrame: Day 84, 252, 336 at pre-dose only. Day 168, 308 at pre-dose and 45 mins post-dose
measure: Maximum Observed Serum Concentration(Cmax) Derived on Day 1, 168 and 308
timeFrame: Day 1, 168, 308 at pre-dose and 45 mins post-dose
measure: Time to Reach the Maximum Concentration After Drug Administration (Tmax) Derived on Day 168 and 308
timeFrame: Day 1, 168, 308 at pre-dose and 45 mins post-dose
measure: Change From Baseline in Body Mass Index (BMI)
timeFrame: Baseline, Week 24, Week 48
measure: Change From Baseline in Weight
timeFrame: Baseline, Week 24, Week 48
measure: Change From Baseline in Lean Body Mass (LBM) Measured by DXA
timeFrame: Baseline, Week 24, Week 48
measure: Change From Baseline in Waist Circumference
timeFrame: Baseline, Week 24, Week 52
measure: Change From Baseline in Waist to Hip Ratio
timeFrame: Baseline, Week 24, Week 52
measure: Change From Baseline in Insulin Resistance (HOMA2-IR)
timeFrame: Baseline. Week 12, Week 36
measure: Immunogenicity Assessed by the Number of Participants Developing Anti-BYM338 Antibodies During the Trial
timeFrame: 392 days
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Novartis Investigative Site
state: California
city: Miami Lakes
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Orlando
country: United States
facility: Novartis Investigative Site
state: Florida
city: Baton Rouge
country: United States
facility: Novartis Investigative Site
state: Louisiana
city: Berlin
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Eatontown
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Merthyr Tydfil
country: United Kingdom
facility: Novartis Investigative Site
state: Mid Glamorgan
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Heymsfield SB, Coleman LA, Miller R, Rooks DS, Laurent D, Petricoul O, Praestgaard J, Swan T, Wade T, Perry RG, Goodpaster BH, Roubenoff R. Effect of Bimagrumab vs Placebo on Body Fat Mass Among Adults With Type 2 Diabetes and Obesity: A Phase 2 Randomized Clinical Trial. JAMA Netw Open. 2021 Jan 4;4(1):e2033457. doi: 10.1001/jamanetworkopen.2020.33457.