Trial Outcomes & Findings for Safety, Pharmacokinetics and Efficacy of Bimagrumab in Overweight and Obese Patients With Type 2 Diabetes (NCT NCT03005288)

Last Updated: 2021-01-05

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

78 participants

Primary outcome timeframe

Baseline, Week 48

Results posted on

2021-01-05

Participant Flow

The study was completed as planned.

Participants were randomized to the study at 1:1 ratio to receive BYM338 10 mg/kg or placebo.

Participant milestones

Participant milestones
Measure	BYM338 10 mg/kg intravenous infusion every four weeks	Placebo intravenous infusion every four weeks
Overall Study STARTED	39	39
Overall Study Safety Analysis Set	37	38
Overall Study Pharmacokinetics (PK) Analysis Set	36	0
Overall Study Pharmacodynamics (PD) Analysis Set	36	36
Overall Study COMPLETED	27	31
Overall Study NOT COMPLETED	12	8

Reasons for withdrawal

Reasons for withdrawal
Measure	BYM338 10 mg/kg intravenous infusion every four weeks	Placebo intravenous infusion every four weeks
Overall Study Withdrawal by Subject	7	5
Overall Study Lost to Follow-up	0	1
Overall Study Adverse Event	5	0
Overall Study Protocol deviation	0	1
Overall Study Physician Decision	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BYM338 10 mg/kg n=37 Participants intravenous infusion every four weeks	Placebo n=38 Participants intravenous infusion every four weeks	Total n=75 Participants Total of all reporting groups
Age, Continuous	60.7 Years STANDARD_DEVIATION 7.50 • n=5 Participants	60.2 Years STANDARD_DEVIATION 8.02 • n=7 Participants	60.4 Years STANDARD_DEVIATION 7.72 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	12 Participants n=7 Participants	35 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	26 Participants n=7 Participants	40 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black Or African American	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	30 Participants n=5 Participants	27 Participants n=7 Participants	57 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic Or Latino	27 Participants n=5 Participants	25 Participants n=7 Participants	52 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic Or Latino	9 Participants n=5 Participants	12 Participants n=7 Participants	21 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 48

Population: Pharmacodynamic (PD) analysis set

Outcome measures

Outcome measures
Measure	BYM338 10 mg/kg n=36 Participants intravenous infusion every four weeks	Placebo n=36 Participants intravenous infusion every four weeks
Change From Baseline in Total Body Fat Mass by Dual Energy X-ray Absorptiometry (DXA) at Week 48	-7.49 kg Interval -8.33 to -6.64	-0.18 kg Interval -0.99 to 0.63

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Pharmacodynamic analysis set

Outcome measures

Outcome measures
Measure	BYM338 10 mg/kg n=36 Participants intravenous infusion every four weeks	Placebo n=36 Participants intravenous infusion every four weeks
Change From Baseline in Total Body Fat Mass by Dual Energy X-ray Absorptiometry (DXA) at Week 24	-5.37 kg Interval -5.96 to -4.78	-0.18 kg Interval -0.75 to 0.39

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 48

Population: Pharmacodynamic analysis set

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.

Outcome measures

Outcome measures
Measure	BYM338 10 mg/kg n=36 Participants intravenous infusion every four weeks	Placebo n=36 Participants intravenous infusion every four weeks
Change From Baseline in HbA1c at Week 24 and 48 week 48	-0.76 percentage change Interval -1.05 to -0.48	0.04 percentage change Interval -0.23 to 0.31
Change From Baseline in HbA1c at Week 24 and 48 week 24	-0.85 percentage change Interval -1.06 to -0.64	0.28 percentage change Interval 0.08 to 0.48

SECONDARY outcome

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

Population: Pharmacokinetics (PK) analysis set - PK samples were only obtained and evaluated for subjects treated with BYM338

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).

Outcome measures

Outcome measures
Measure	BYM338 10 mg/kg n=36 Participants intravenous infusion every four weeks	Placebo intravenous infusion every four weeks
The Trough Observed Analyte Concentration (Ctrough) of Repeat Doses of BYM338 10 mg/kg on Day 84, 168, 252, 308 and 336 Day 84	25.3 μg/mL Standard Deviation 6.20	—
The Trough Observed Analyte Concentration (Ctrough) of Repeat Doses of BYM338 10 mg/kg on Day 84, 168, 252, 308 and 336 Day 168	27.5 μg/mL Standard Deviation 8.37	—
The Trough Observed Analyte Concentration (Ctrough) of Repeat Doses of BYM338 10 mg/kg on Day 84, 168, 252, 308 and 336 Day 252	31.0 μg/mL Standard Deviation 11.2	—
The Trough Observed Analyte Concentration (Ctrough) of Repeat Doses of BYM338 10 mg/kg on Day 84, 168, 252, 308 and 336 Day 308	29.9 μg/mL Standard Deviation 11.0	—
The Trough Observed Analyte Concentration (Ctrough) of Repeat Doses of BYM338 10 mg/kg on Day 84, 168, 252, 308 and 336 Day 336	27.8 μg/mL Standard Deviation 10.9	—

SECONDARY outcome

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

Population: Pharmacokinetics (PK) analysis set - PK samples were only obtained and evaluated for subjects treated with BYM338

Cmax is the observed maximum plasma concentration following administration (μg/mL).

Outcome measures

Outcome measures
Measure	BYM338 10 mg/kg n=36 Participants intravenous infusion every four weeks	Placebo intravenous infusion every four weeks
Maximum Observed Serum Concentration(Cmax) Derived on Day 1, 168 and 308 Day 1	283 μg/mL Standard Deviation 32.0	—
Maximum Observed Serum Concentration(Cmax) Derived on Day 1, 168 and 308 Day 168	292 μg/mL Standard Deviation 45.3	—
Maximum Observed Serum Concentration(Cmax) Derived on Day 1, 168 and 308 Day 308	271 μg/mL Standard Deviation 31.1	—

SECONDARY outcome

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

Population: Pharmacokinetics (PK) analysis set - PK samples were only obtained and evaluated for subjects treated with BYM338

Tmax is the time to reach peak or maximum concentration (h) after the drug administration.

Outcome measures

Outcome measures
Measure	BYM338 10 mg/kg n=36 Participants intravenous infusion every four weeks	Placebo intravenous infusion every four weeks
Time to Reach the Maximum Concentration After Drug Administration (Tmax) Derived on Day 168 and 308 Day 1	0.750 hr Interval 0.683 to 0.917	—
Time to Reach the Maximum Concentration After Drug Administration (Tmax) Derived on Day 168 and 308 Day 168	0.750 hr Interval 0.75 to 1.05	—
Time to Reach the Maximum Concentration After Drug Administration (Tmax) Derived on Day 168 and 308 Day 308	0.750 hr Interval 0.75 to 1.38	—

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 48

Population: Pharmacodynamic analysis set

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)

Outcome measures

Outcome measures
Measure	BYM338 10 mg/kg n=36 Participants intravenous infusion every four weeks	Placebo n=36 Participants intravenous infusion every four weeks
Change From Baseline in Body Mass Index (BMI) week 24	-1.50 Kg/m^2 Interval -1.77 to -1.23	-0.17 Kg/m^2 Interval -0.43 to 0.1
Change From Baseline in Body Mass Index (BMI) week 48	-2.19 Kg/m^2 Interval -2.6 to -1.78	-0.28 Kg/m^2 Interval -0.67 to 0.11

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 48

Population: Pharmacodynamic analysis set

Body weight was measured to the nearest 0.1 kilogram (kg) in indoor clothing without shoes. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	BYM338 10 mg/kg n=36 Participants intravenous infusion every four weeks	Placebo n=36 Participants intravenous infusion every four weeks
Change From Baseline in Weight week 24	-3.99 Kg Interval -4.79 to -3.19	-0.57 Kg Interval -1.34 to 0.21
Change From Baseline in Weight week 48	-5.90 Kg Interval -7.08 to -4.71	-0.79 Kg Interval -1.92 to 0.33

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 48

Population: Pharmacodynamic analysis set

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.

Outcome measures

Outcome measures
Measure	BYM338 10 mg/kg n=36 Participants intravenous infusion every four weeks	Placebo n=36 Participants intravenous infusion every four weeks
Change From Baseline in Lean Body Mass (LBM) Measured by DXA week 24	1.72 Kg Interval 1.25 to 2.19	0.23 Kg Interval -0.23 to 0.68
Change From Baseline in Lean Body Mass (LBM) Measured by DXA week 48	1.70 Kg Interval 1.14 to 2.26	-0.44 Kg Interval -0.97 to 0.09

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 52

Population: Pharmacodynamic analysis set

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.

Outcome measures

Outcome measures
Measure	BYM338 10 mg/kg n=36 Participants intravenous infusion every four weeks	Placebo n=36 Participants intravenous infusion every four weeks
Change From Baseline in Waist Circumference week 24	-5.04 cm Interval -5.87 to -4.2	-0.95 cm Interval -1.75 to -0.14
Change From Baseline in Waist Circumference week 52	-9.00 cm Interval -10.3 to -7.68	0.45 cm Interval -0.79 to 1.69

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 52

Population: Pharmacodynamic analysis set

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.

Outcome measures

Outcome measures
Measure	BYM338 10 mg/kg n=36 Participants intravenous infusion every four weeks	Placebo n=36 Participants intravenous infusion every four weeks
Change From Baseline in Waist to Hip Ratio week 24	-0.02 ratio Interval -0.03 to -0.01	-0.01 ratio Interval -0.01 to 0.0
Change From Baseline in Waist to Hip Ratio week 52	-0.05 ratio Interval -0.06 to -0.04	0.01 ratio Interval 0.0 to 0.02

SECONDARY outcome

Timeframe: Baseline. Week 12, Week 36

Population: Pharmacodynamic analysis set

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 \[https://www.dtu.ox.ac.uk/homacalculator/\].

Outcome measures

Outcome measures
Measure	BYM338 10 mg/kg n=36 Participants intravenous infusion every four weeks	Placebo n=36 Participants intravenous infusion every four weeks
Change From Baseline in Insulin Resistance (HOMA2-IR) week 12	0.10 Insulin Resistance (IR) Score Interval -0.17 to 0.37	0.76 Insulin Resistance (IR) Score Interval 0.5 to 1.02
Change From Baseline in Insulin Resistance (HOMA2-IR) week 36	-0.09 Insulin Resistance (IR) Score Interval -0.44 to 0.25	0.57 Insulin Resistance (IR) Score Interval 0.24 to 0.9

SECONDARY outcome

Timeframe: 392 days

Population: Safety analysis set

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.

Outcome measures

Outcome measures
Measure	BYM338 10 mg/kg n=37 Participants intravenous infusion every four weeks	Placebo n=38 Participants intravenous infusion every four weeks
Immunogenicity Assessed by the Number of Participants Developing Anti-BYM338 Antibodies During the Trial Confirmed with positive immunogenicity	2 Participants	4 Participants

Adverse Events

BYM338 10 mg/kg

Serious events: 3 serious events

Other events: 31 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	BYM338 10 mg/kg n=37 participants at risk intravenous infusion every four weeks	Placebo n=38 participants at risk intravenous infusion every four weeks
Cardiac disorders Acute coronary syndrome	0.00% 0/37 • Adverse events were collected throughout the study for 56 weeks which includes the treatment period of 48 weeks and the follow-up period of 8 weeks.	2.6% 1/38 • Adverse events were collected throughout the study for 56 weeks which includes the treatment period of 48 weeks and the follow-up period of 8 weeks.
Cardiac disorders Acute myocardial infarction	0.00% 0/37 • Adverse events were collected throughout the study for 56 weeks which includes the treatment period of 48 weeks and the follow-up period of 8 weeks.	2.6% 1/38 • Adverse events were collected throughout the study for 56 weeks which includes the treatment period of 48 weeks and the follow-up period of 8 weeks.
Gastrointestinal disorders Abdominal pain upper	2.7% 1/37 • Adverse events were collected throughout the study for 56 weeks which includes the treatment period of 48 weeks and the follow-up period of 8 weeks.	0.00% 0/38 • Adverse events were collected throughout the study for 56 weeks which includes the treatment period of 48 weeks and the follow-up period of 8 weeks.
Gastrointestinal disorders Impaired gastric emptying	0.00% 0/37 • Adverse events were collected throughout the study for 56 weeks which includes the treatment period of 48 weeks and the follow-up period of 8 weeks.	2.6% 1/38 • Adverse events were collected throughout the study for 56 weeks which includes the treatment period of 48 weeks and the follow-up period of 8 weeks.
Gastrointestinal disorders Pancreatitis	2.7% 1/37 • Adverse events were collected throughout the study for 56 weeks which includes the treatment period of 48 weeks and the follow-up period of 8 weeks.	0.00% 0/38 • Adverse events were collected throughout the study for 56 weeks which includes the treatment period of 48 weeks and the follow-up period of 8 weeks.
Infections and infestations Cellulitis	0.00% 0/37 • Adverse events were collected throughout the study for 56 weeks which includes the treatment period of 48 weeks and the follow-up period of 8 weeks.	2.6% 1/38 • Adverse events were collected throughout the study for 56 weeks which includes the treatment period of 48 weeks and the follow-up period of 8 weeks.
Infections and infestations Pneumonia	2.7% 1/37 • Adverse events were collected throughout the study for 56 weeks which includes the treatment period of 48 weeks and the follow-up period of 8 weeks.	0.00% 0/38 • Adverse events were collected throughout the study for 56 weeks which includes the treatment period of 48 weeks and the follow-up period of 8 weeks.
Injury, poisoning and procedural complications Thermal burn	0.00% 0/37 • Adverse events were collected throughout the study for 56 weeks which includes the treatment period of 48 weeks and the follow-up period of 8 weeks.	2.6% 1/38 • Adverse events were collected throughout the study for 56 weeks which includes the treatment period of 48 weeks and the follow-up period of 8 weeks.
Investigations Lipase increased	2.7% 1/37 • Adverse events were collected throughout the study for 56 weeks which includes the treatment period of 48 weeks and the follow-up period of 8 weeks.	0.00% 0/38 • Adverse events were collected throughout the study for 56 weeks which includes the treatment period of 48 weeks and the follow-up period of 8 weeks.

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER