E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
|
E.1.1.1 | Medical condition in easily understood language |
Diabetes Mellitus, Type 2 |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the treatment effect of bimagrumab on total body fat mass |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate the treatment effect of bimagrumab on total body fat mass after 6 months of treatment
- To evaluate the treatment effect of bimagrumab on glycemic control and parameters of insulin sensitivity
- To evaluate the safety and tolerability of bimagrumab in overweight and obese subjects with type 2 diabetes
- To evaluate the pharmacokinetics of repeat doses of bimagrumab in overweight and obese subjects with type 2 diabetes
- To evaluate the immunogenic response to repeat dosing of bimagrumab in overweight and obese subjects with type 2 diabetes
- To evaluate the treatment effect of bimagrumab on anthropometric body measurements and on lean body mass |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Type 2 diabetes with HbA1c between 7% and 10% at screening with stable treatment for 3 months prior to randomization
- Body Mass Index of 28 to 40 kg/m2 at screening
- Body weight between 65 and 140 kg at screening |
|
E.4 | Principal 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 ofr 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)
- uncontrolled thyroid disease. Stable euthyroid patients on stable thyroid replacement therapy for at least 3 months of
screening are allowed
- 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] |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change in total body fat mass measured by DXA at week 48 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Mean change from baseline in HbA1c [Week 24 and Week 48]. Plasma samples are taken. A model will be used to describe HbA1c over time and the change in HbA1c at Week 24 and Week 48 will be estimated from that model.
- Pharmacokinetics of bimagrumab: PK samples - pre (Ctrough) and post dose during treatment and follow -up periods. Tmax and Cmax Day 1,
Day 168, and Day 308 will be derived.
- Change in body weight, BMI, waist circumference, waist-to-hip ratio and lean body mass as measured by DXA [Baseline, Week 24, Week 48]. Change on anthropometric body measurements and lean body mass from baseline at Week 24 and Week 48.
- Anti drug antibodies pre-dose, during treatment and at the end of study.
- Change in total body fat mass as measured by DXA [Week 24].
- Mean Change from baseline in insulin resistance [Week 24 and Week 48]. Plasma samples are taken and insulin resistance is measured via the homeostatic model assessment using a computer to model insulin sensitivity. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
As defined in section E.5.2 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 2 |