E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recent-onset type 1 diabetes mellitus |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045228 |
E.1.2 | Term | Type I diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 |
The primary objective of this study is to assess relative to placebo, the efficacy of teplizumab when administered according to 3 different teplizumab dosing regimens in subjects with recent-onset Type 1 Diabetes Mellitus (within 12 weeks of presentation of first signs and symptoms of disease to a physician). All regimens were administered in addition to standard of care. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to assess the durability of clinical benefit and the safety and tolerability of teplizumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must have met all of the following criteria:
- Diagnosis of diabetes mellitus according to the American Diabetes Association (ADA) criteria.
- Randomization on Study Day 0 within 12 weeks of first visit to any physician for symptoms or signs of diabetes
- Detectable fasting or stimulated C-peptide level (above the lower limit of the reportable range of the assay) at screening
- Diagnosis of T1DM as evidenced by one positive result on testing for any of the following antibodies at screening :
a. Islet-cell autoantibodies 512 (ICA512)/islet antigen-2 (IA-2),
b. Glutamic acid decarboxylase (GAD) autoantibodies, or
c. Insulin autoantibodies (in subjects on insulin for more than 2 weeks, ICA512/IA-2 or GAD must be positive)
- Subjects 8–35 years old; France only: Subjects 18–35 years old
- Body weight ≥ 36 Kg
- BSA ≤2.4 m2 (Interactive Voice Response System [IVRS] will be used to calculate BSA using the Mosteller formula )
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E.4 | Principal exclusion criteria |
Subjects must not have had any of the following criteria:
- Prior administration of a monoclonal antibody—within the 1 year before randomization at Study Day 0
- Participation in any type of therapeutic drug or vaccine clinical trial within the last 12 weeks before randomization at Study Day 0
- Prior murine OKT®3 treatment or other anti-CD3 treatment
- Current therapy with GLP-1 receptor agonists (e.g., exenatide or pramlintide), or any other agents that might stimulate pancreatic beta cell regeneration or insulin secretion
- Current treatment with oral antidiabetic agents
- Evidence of active infection
- History of or positive test for human immunodeficiency virus (HIV)
- History of or positive tests for hepatitis B, C or D
- Evidence of active or latent tuberculosis (TB), which may include a positive purified protein derivative (PPD) skin test result (≥ 10 mm induration); a chest X-ray consistent with TB or household contact with a person with active TB, unless appropriate isoniazid (INH) prophylaxis for tuberculosis (TB) was previously given
- Vaccination with a live virus or organism within the 8 weeks before randomization continuing through Week 52 (Study Day 364) of the study:
a. Influenza vaccinations with a killed virus, including booster vaccinations, within 4 weeks before or after each dosing course.
b. Vaccination with other antigens or killed organisms within 8 weeks before or after each dosing course
- Any infectious mononucleosis-like illness within the 6 months before randomization
- Serologic or clinical evidence of acute infection with Epstein-Barr virus (EBV), including a positive Epstein-Barr virus (EBV) immunoglobulin M (IgM). (Viral load does not have to be positive)
- Serologic evidence of acute infection with cytomegalovirus (CMV), defined as a positive cytomegalovirus (CMV) immunoglobulin G (IgG) and a positive viral load
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E.5 End points |
E.5.1 | Primary end point(s) |
1. The proportion of subjects who have both a total daily insulin dose < 0.5 Units (U)/kilogram (Kg)/day and hemoglobin A1c (HbA1c) level < 6.5% at Study Day 364
2. The mean HbA1c change from baseline to Study Day 364 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary endpoints are assessed according to the protocol |
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E.5.2 | Secondary end point(s) |
The secondary endpoints of the study are:
• The mean fasting C-peptide change from baseline to Study Day 364
• Incidence of total, major, minor and nocturnal hypoglycemia at Study Day 364
• Mean number of daily insulin injections received at Study Day 364 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints are assessed at multiple timepoints according to the protocol |
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
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 |
Immunologic parameters; Patient Reported Outcomes |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
Belgium |
Czech Republic |
Finland |
France |
Germany |
India |
Israel |
Italy |
Mexico |
Netherlands |
Poland |
Romania |
Spain |
Ukraine |
United Kingdom |
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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
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The End of Trial is defined as database lock, following last patient last visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |