E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 1 diabetes |
Typ 1 diabetes |
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E.1.1.1 | Medical condition in easily understood language |
Type 1 diabetes |
Typ 1 diabetes |
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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 | LLT |
E.1.2 | Classification code | 10012594 |
E.1.2 | Term | Diabetes |
E.1.2 | System Organ Class | 100000004861 |
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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 |
Primary Objective
To investigate the safety and tolerance after a repeated allogeneic infusion of WJMSCs intravenously in adult patients diagnosed with type 1 diabetes after one year following the repeated treatment.
Safety Objective
To investigate the safety and tolerance after a repeated allogeneic infusion of WJMSCs intravenously in adult patients diagnosed with type 1 diabetes after 5 year following the repeated treatment. |
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives
Study changes in beta-cell function, metabolic control and Diabetes Treatment Satisfaction during one year following the repeated treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. A new written informed consent for participation of the study is required to be given before undergoing any study-specific procedures.
2. Only patients that have previously been dosed by the IMP according to protocol Protrans-1 are eligible for a second dose of Protrans.
3. No identified IMP related on-going adverse event, neither history of any adverse event that is evaluated potentially to be related to the previous IMP dosing in Protrans I.
4. Clinical history compatible with type 1 diabetes diagnosed less than 3 years before enrolment. This also includes control patients not receiving IMP.
5. Only male patients between 18-41 years of age will be included.
6. Mentally stable and, in the opinion of the investigator, able to comply with the procedures of the study protocol.
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E.4 | Principal exclusion criteria |
1. Inability to provide informed consent
2. Patients with body mass index (BMI) > 30, or weight >100 kg
3. Patients with weight <50 kg
4. Patients with unstable cardiovascular status incl. NYHA class III/IV or symptoms of angina pectoris.
1. Inability to provide informed consent
2. Patients with body mass index (BMI) > 30, or weight >100 kg
3. Patients with weight <50 kg
4. Patients with unstable cardiovascular status incl. NYHA class III/IV or symptoms of angina pectoris.
5. Patients with uncontrolled hypertension (≥160/105 mmHg).
6. Patients with active infections unless treatment is not judged necessary by the investigators
7. Patients with latent or previous as well as on-going therapy against tuberculosis, or exposed to tuberculosis or has travelled in areas with high risk of tuberculosis or mycosis within the last 3 months.
8. Patients with serological evidence of infection with HIV, Treponema pallidum, hepatitis B antigen (patients with serology consistent with previous vaccination and a history of vaccination are acceptable) or hepatitis C.
9. Patients with any immune suppressive treatment
10. Patients with known demyelinating disease or with symptoms or physical examination findings consistent with possible demyelinating disease.
11. Patients with known, or previous, malignancy.
12. Taking oral anti-diabetic therapies or any other concomitant medication which may interfere with glucose regulation other than insulin
13. Patients with GFR <80 ml/min/1.73 m2 body surface
14. Patients with proliferative retinopathy
15. Patient with any condition or any circumstance that in the opinion of the investigator would make it unsafe to undergo treatment with MSC.
16. Known hypersensitivity against any excipients, i.e. dimethyl sulfoxide (DMSO). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint
The primary endpoint in this study is; safety parameters include adverse events and hypoglycemia, allergic
reactions, ophthalmologic examination, ECG, vital signs, laboratory assessments at day 372.
Safety Endpoint
The safety endpoint of this study is the safety and tolerance after a repeated allogeneic infusion of WJMSCs
intravenously in adult patients diagnosed with type 1 diabetes after 5 year. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary Endpoint:
At day 372
Safety Endpoint
During the whole trial 5 years. |
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E.5.2 | Secondary end point(s) |
Secondary Endpoint:
Delta-change of C-peptide Area Under the Curve (AUC) (0-120 min) for Mixed Meal Tolerance Test (MMTT)
at day 372 following WJMSC infusion when compared to test performed before start of treatment when
compared to control patients.
• Number of patients insulin independent (ADA criteria) at day 372.
• Number of patients with daily insulin needs <0.25U/kg at day 372.
• Insulin requirement/kg BW at day 372.
• HbA1c at day 372.
• Glucose variability (mean amplitude of glycaemic excursions and glycaemic lability index) and
hypo/hyper glycaemia duration derived from the continuous glucose monitoring system® at day
372.
• Delta change of levels of fasting C-peptide at day 372 when compared to test before start of
treatment.
• Numbers of patients with peak C-peptide >0.20 nmol/l, in response to the MMTT, at day 372.
• To study changes during one year following treatment in:
-Insulin doses
-HbA1c
-Glucose variability
-Diabetes Treatment Satisfaction |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints:
Day 372 following WJMSC
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
P1 pts 1-3: 25x10e6 cells,pts 4-6:100 x10e6 cells,pts 7-9:200, control group 6 patients= non treated |
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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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 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
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |