E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 1 diabetes in children and adolescents |
|
E.1.1.1 | Medical condition in easily understood language |
Type 1 diabetes in children and adolescents |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
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 |
• Evaluate the safety and influence of treatment with GAD-Alum (Diamyd) plus Vitamin D plus Ibuprofen on preservation of residual insulin secretion in recently-diagnosed Type 1 diabetes.
• Evaluate how the abovementioned treatments influencers the immune system of the patients and interact with any viral infections.
• Evaluate the safety and influence of treatment with double dose of GAD-Alum (Diamyd) plus Vitamin D on the immune system and on preservation of residual insulin secretion in recently-diagnosed Type 1 diabetes
|
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Informed consent given by patients and guardians/parents
• Type 1 diabetes according to the ADA classification with < 4 months diabetes duration
• Age 10.00 -17.99 years at Diagnosis of Type 1 diabetes
• Fasting C-peptide >0.12 nmol/ml
• Pos GADA but < 50 000 random units
|
|
E.4 | Principal exclusion criteria |
• Previous or current treatment with immunosuppressant therapy (although topical or inhaled steroids are accepted)
• Continuous treatment with any inflammatory drug ( sporadic treatment eg because of headache or in connection with fever a few days will be accepted)
• Treatment with any oral or injected anti-diabetic medications other than insulin
• Treatment with any vitamins, marketed or not, or unwilling to abstain from such medication during the trial.
• A history of anaemia or significantly abnormal haematology results at screening
• A history of epilepsy, head trauma or cerebro-vascular accident, or clinical features of continuous motor unit activity in proximal muscles
• Clinically significant history of acute reaction to vaccines or other drugs in the past
• Treatment with any vaccine within 4 months prior to planned first study drug dose or planned treatment with vaccine up to 4 months after the last injection with study drug, including influenza vaccine
• Participation in other clinical trials with a new chemical entity within the previous 3 months
• Inability or unwillingness to comply with the provisions of this protocol
• A history of alcohol or drug abuse
• A significant illness other than diabetes within 2 weeks prior to first dosing
• Known human immunodeficiency virus (HIV) or hepatitis
• Females who are lactating or pregnant (for females who have started menstruating the possibility of pregnancy must be excluded by urine βHCG on-site within 24 hours prior to the GAD-alum treatment)
• Males or females not willing to use adequate contraception, if sexually active, until 1 year after the last GAD-alum treatment
• Presence of associated serious disease or condition, including active skin infections that preclude subcutaneous injection, which in the opinion of the investigator makes the patient non-eligible for the study.
• Deemed by the investigator not being able to follow instructions and/or follow the study protocol
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Th2-deviation of cellmediated immune response seen as increased ratio of IL-5,10,13 in comparison with IFNgamma, TNFalfa, and IL-1beta, IL17, and increase of T-regulatory cells. At baseline and subsequent visits.
• Inflammatory markers such as IL-1,IL-2, IL-1beta, IL-17
• Change in C-peptide (90 minute value and AUCmean 0-120 min) during an MMTT from baseline to month 6, 15 resp to month 30.
• Fasting C-peptide, change between baseline and month 6, 15 resp 30.
• Proportion of patients with a stimulated maximum C-peptide level above 0.2 nmol/L at baseline and month 6, 15 resp 30.
• Hemoglobin A1c (HbA1c), change between baseline and subsequent visits
• Exogenous insulin dose per kg body weight and 24 hours, change between baseline and subsequent visits
The safety assessment includes occurrence of adverse events (AEs), laboratory measurements, brief physical examination including neurological assessments |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After completion of the first part of the Intervention study period , the treatment code will be revealed already after 6 months to the statistician and the sponsor, for statistical analysis of the efficacy variables and safety data. (The results will be used for design of the main DIABGAD trial.) Both patients and the physicians treating the patients will be kept blinded for individual treatment code for the entire study period (30 months). |
|
E.5.2 | Secondary end point(s) |
This is a pilot trial, and we do not separate primary and seconday endpoints. Please see above. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
After completion of the first part of the Intervention study period , the treatment code will be revealed already after 6 months to the statistician and the sponsor, for statistical analysis of the efficacy variables and safety data. (The results will be used for design of the main DIABGAD trial.) Both patients and the physicians treating the patients will be kept blinded for individual treatment code for the entire study period (30 months). |
|
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 | No |
E.6.7 | Pharmacodynamic | No |
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 | No |
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 | 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 | 10 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
|
The end of the clinicdal study is the last visit of the last patient, but then the study is not ended fully until we have anlyzed the data , both clinical and laboratory. |
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | |