Safety, Pharmacokinetics and Efficacy of Bimagrumab in Overweight and Obese Patients With Type 2 Diabetes

NCT03005288 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CBYM338X2211
• Study Type: interventional
• Target: 78
• Locations: 2 countries
• Sites: 9

Brief Summary

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

Conditions

Diabetes Mellitus, Type 2

Keywords

type 2 diabetes; obesity; DXA; MRI

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Total Body Fat Mass by Dual Energy X-ray Absorptiometry (DXA) at Week 48

  Dual energy X-ray absorptiometry (DXA) was used to assess changes in body composition, including total fat and lean body mass (FM and LBM) and appendicular skeletal fat and muscle mass (aFM and aLBM). DXA instruments had a source that generated x-rays split into two energies which measured bone mineral mass and soft tissue from which fat and fat-free mass (or lean body mass) were estimated.

  Baseline, Week 48

Secondary Outcomes (12)

• Change From Baseline in Total Body Fat Mass by Dual Energy X-ray Absorptiometry (DXA) at Week 24

  Baseline, Week 24

• Change From Baseline in HbA1c at Week 24 and 48

  Baseline, Week 24, Week 48

• The Trough Observed Analyte Concentration (Ctrough) of Repeat Doses of BYM338 10 mg/kg on Day 84, 168, 252, 308 and 336

  Day 84, 252, 336 at pre-dose only. Day 168, 308 at pre-dose and 45 mins post-dose

• Maximum Observed Serum Concentration(Cmax) Derived on Day 1, 168 and 308

  Day 1, 168, 308 at pre-dose and 45 mins post-dose

• Time to Reach the Maximum Concentration After Drug Administration (Tmax) Derived on Day 168 and 308

  Day 1, 168, 308 at pre-dose and 45 mins post-dose

Study Arms (2)

BYM338 10 mg/kg

EXPERIMENTAL

Bimagrumab (BYM338) 10 mg/kg up to maximum 1200 mg, every 4 weeks until week 44 (12 doses)

Drug: BYM338 10 mg/kg

Placebo

PLACEBO COMPARATOR

Placebo, every 4 weeks until week 44 (12 doses)

Other: Placebo

Interventions

BYM338 10 mg/kg DRUG

intravenous infusion every four weeks

Also known as: Bimagrumab

BYM338 10 mg/kg

Placebo OTHER

intravenous infusion every four weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 \[estimated glomerular filtration rate (GFR) \< 30 mL/min\];

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (9)

Novartis Investigative Site

Anaheim, California, 92801, United States

Location

Novartis Investigative Site

Miami, Florida, 33126, United States

Location

Novartis Investigative Site

Miami, Florida, 33143, United States

Location

Novartis Investigative Site

Miami Lakes, Florida, 33014, United States

Location

Novartis Investigative Site

Orlando, Florida, 32804, United States

Location

Novartis Investigative Site

Baton Rouge, Louisiana, 70808, United States

Location

Novartis Investigative Site

Berlin, New Jersey, 08009, United States

Location

Novartis Investigative Site

Eatontown, New Jersey, 07724, United States

Location

Novartis Investigative Site

Merthyr Tydfil, Mid Glamorgan, CF484DR, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33439265 DERIVED

Related Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity

Interventions

bimagrumab

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2016
• First Posted: December 29, 2016
• Study Start: February 1, 2017
• Primary Completion: March 21, 2019
• Study Completion: May 8, 2019
• Last Updated: January 5, 2021
• Results First Posted: June 4, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share

Locations

GB (1); US (8)