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

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ClinicalTrials.gov Identifier: NCT03005288
Recruitment Status : Completed
First Posted : December 29, 2016
Results First Posted : June 4, 2020
Last Update Posted : January 5, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: BYM338 10 mg/kg Other: Placebo Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 78 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : February 1, 2017
Actual Primary Completion Date : March 21, 2019
Actual Study Completion Date : May 8, 2019

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: BYM338 10 mg/kg
Bimagrumab (BYM338) 10 mg/kg up to maximum 1200 mg, every 4 weeks until week 44 (12 doses)
 Drug: BYM338 10 mg/kg
intravenous infusion every four weeks
Other Name: Bimagrumab
Placebo Comparator: Placebo
Placebo, every 4 weeks until week 44 (12 doses)
 Other: Placebo
intravenous infusion every four weeks


Outcome Measures
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Primary Outcome Measures :
  1. Change From Baseline in Total Body Fat Mass by Dual Energy X-ray Absorptiometry (DXA) at Week 48 [ Time Frame: Baseline, 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.


Secondary Outcome Measures :
  1. Change From Baseline in Total Body Fat Mass by Dual Energy X-ray Absorptiometry (DXA) at Week 24 [ Time Frame: Baseline, Week 24 ]
    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.

  2. Change From Baseline in HbA1c at Week 24 and 48 [ Time Frame: Baseline, Week 24, Week 48 ]
    HbA1c reflects average glucose concentrations over the past 3 months and therefore provides a useful index of the glycemic control of bimagrumab over that time period. It is a standard endpoint used to assess the glycemic efficacy of any anti-diabetic medication. HbA1c is a key glycemic parameter which correlates with reduction of risk of diabetic complications.

  3. The Trough Observed Analyte Concentration (Ctrough) of Repeat Doses of BYM338 10 mg/kg on Day 84, 168, 252, 308 and 336 [ Time Frame: Day 84, 252, 336 at pre-dose only. Day 168, 308 at pre-dose and 45 mins post-dose ]
    The trough observed analyte concentration (Ctrough) is the concentration that is just prior to the beginning of, or at the end of, a dosing interval (μg/mL).

  4. Maximum Observed Serum Concentration(Cmax) Derived on Day 1, 168 and 308 [ Time Frame: Day 1, 168, 308 at pre-dose and 45 mins post-dose ]
    Cmax is the observed maximum plasma concentration following administration (μg/mL).

  5. Time to Reach the Maximum Concentration After Drug Administration (Tmax) Derived on Day 168 and 308 [ Time Frame: Day 1, 168, 308 at pre-dose and 45 mins post-dose ]
    Tmax is the time to reach peak or maximum concentration (h) after the drug administration.

  6. Change From Baseline in Body Mass Index (BMI) [ Time Frame: Baseline, Week 24, Week 48 ]
    Body Mass Index (BMI) was determined by height and weight measurements at week 24 and 48. A negative change from baseline indicates improvement. BMI was calculated as (Body weight (kg)/ [Height (m)]^2)

  7. Change From Baseline in Weight [ Time Frame: Baseline, Week 24, Week 48 ]
    Body weight was measured to the nearest 0.1 kilogram (kg) in indoor clothing without shoes. A negative change from baseline indicates improvement.

  8. Change From Baseline in Lean Body Mass (LBM) Measured by DXA [ Time Frame: Baseline, Week 24, Week 48 ]

    Lean body mass (LBM) is a part of body composition defined as the difference between total body weight and body fat weight. This means that it counts the mass of all organs except body fat, including bones, muscles, blood, skin, and everything else.

    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.


  9. Change From Baseline in Waist Circumference [ Time Frame: Baseline, Week 24, Week 52 ]
    Waist circumference is the length in cm of the circumference to the nearest 0.1 cm at the level of the umbilicus with the subject in the upright position. A negative change indicates improvement.

  10. Change From Baseline in Waist to Hip Ratio [ Time Frame: Baseline, Week 24, Week 52 ]
    Hip circumference was measured at the greatest protrusion of the buttocks. Combined with waist circumference, the waist-to-hip ratio was derived during data analysis.

  11. Change From Baseline in Insulin Resistance (HOMA2-IR) [ Time Frame: Baseline. Week 12, Week 36 ]
    Blood samples were collected to analyze insulin resistance. The homeostasis model assessment computational method was used to estimate insulin resistance (HOMA2-IR) from fasting plasma glucose and insulin. The HOMA2-IR is the reciprocal of insulin sensitivity (%S), as a percentage of a normal reference population (normal young adult). Higher numbers indicate higher insulin resistance. No established cutoffs are indicating impaired resistance. HOMA2-IR was calculated using an online calculator [https://www.dtu.ox.ac.uk/homacalculator/].

  12. Immunogenicity Assessed by the Number of Participants Developing Anti-BYM338 Antibodies During the Trial [ Time Frame: 392 days ]
    Describes the number of participants tested positive for anti-BYM338 antibodies after the start of bimagrumab (BYM338) treatment. A validated bridging enzyme-linked immunosorbent assay (ELISA) was used for the confirmation of the presence of anti-BYM338 antibodies in human serum.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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];
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03005288


Locations
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United States, California
Novartis Investigative Site
Anaheim, California, United States, 92801
United States, Florida
Novartis Investigative Site
Miami Lakes, Florida, United States, 33014
Novartis Investigative Site
Miami, Florida, United States, 33126
Novartis Investigative Site
Miami, Florida, United States, 33143
Novartis Investigative Site
Orlando, Florida, United States, 32804
United States, Louisiana
Novartis Investigative Site
Baton Rouge, Louisiana, United States, 70808
United States, New Jersey
Novartis Investigative Site
Berlin, New Jersey, United States, 08009
Novartis Investigative Site
Eatontown, New Jersey, United States, 07724
United Kingdom
Novartis Investigative Site
Merthyr Tydfil, Mid Glamorgan, United Kingdom, CF484DR
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] January 17, 2019
Statistical Analysis Plan  [PDF] March 18, 2019

More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03005288    
Other Study ID Numbers: CBYM338X2211
First Posted: December 29, 2016    Key Record Dates
Results First Posted: June 4, 2020
Last Update Posted: January 5, 2021
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
type 2 diabetes
obesity
DXA
MRI
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Overweight
Glucose Metabolism Disorders
Metabolic Diseases
 Endocrine System Diseases
Overnutrition
Nutrition Disorders
Body Weight