Wharton´s Jelly Derived Mesenchymal Stromal Cell Repeated Treatment of Adult Patients Diagnosed With Type I Diabetes

Study Overview
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Brief Summary
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An open label, parallel single centre trial of Wharton's Jelly derived allogenic mesenchymal stromal cells repeated treatment to preserve endogenous insulin production in adult patients diagnosed with type 1 diabetes

Detailed Description
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This is a phase (I)/II study, and the purpose of this study is to determine whether, in adult patients diagnosed for type 1 diabetes, a repeated allogeneic infusion of WJMSCs is safe and to study changes in beta-cell function, metabolic control and Diabetes Treatment Satisfaction. The study population will consist of 18 adult male patients, 18-41 years of age (inclusive at both ends) diagnosed (<3,5 years) with type 1 diabetes mellitus.

Official Title
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An Open Label, Parallel Single Center Trial of Wharton's Jelly Derived Allogeneic Mesenchymal Stromal Cells Repeatedly Treated to Preserve Endogenous Insulin Production in Adult Patients Diagnosed With Type 1 Diabetes

Conditions
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Type1diabetes

Intervention / Treatment
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* Drug: ProTrans
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A new written informed consent for participation of the study is required to be given before undergoing any study-specific procedures. Only patients that have previously been dosed by the IMP according to protocol Protrans-1 are eligible for a second dose of Protrans. 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. Clinical history compatible with type 1 diabetes diagnosed less than 3 years before enrolment. This also includes control patients not receiving IMP. Only male patients between 18-41 years of age will be included. Mentally stable and, in the opinion of the investigator, able to comply with the procedures of the study protocol. Exclusion Criteria: Inability to provide informed consent Patients with body mass index (BMI) > 30, or weight >100 kg Patients with weight <50 kg Patients with unstable cardiovascular status incl. NYHA class III/IV or symptoms of angina pectoris. Patients with uncontrolled hypertension (≥160/105 mmHg). Patients with active on-going infections. 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. 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. Patients with any immune suppressive treatment Patients with known demyelinating disease or with symptoms or physical examination findings consistent with possible demyelinating disease. Patients with known, or previous, malignancy. Taking oral anti-diabetic therapies or any other concomitant medication which may interfere with glucose regulation other than insulin Patients with GFR <80 ml/min/1.73 m2 body surface Patients with proliferative retinopathy Patient with any condition or any circumstance that in the opinion of the investigator would make it unsafe to undergo treatment with MSC. Known hypersensitivity against any excipients, i.e. dimethyl sulfoxide (DMSO).- This criterion is only applicable to patients which receive study drug.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 41 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose<br>3 patients receiving low dose | Drug: ProTrans<br>* Single infusion of 25, 100 or 200 million cells per patient.<br>* Other names: Allogeneic transplantation with WJMSCs;|
| Experimental: Medium dose<br>3 patients receiving medium dose | Drug: ProTrans<br>* Single infusion of 25, 100 or 200 million cells per patient.<br>* Other names: Allogeneic transplantation with WJMSCs;|
| Experimental: High dose<br>3 patients receiving high dose | Drug: ProTrans<br>* Single infusion of 25, 100 or 200 million cells per patient.<br>* Other names: Allogeneic transplantation with WJMSCs;|
| Sham Comparator: Control<br>6 patients | Drug: Placebo<br>* Placebo Comparator: Sham transplantation (placebo) Single infusion with albumin and dmso in sodium chloride (identical concentrations as active treatment)<br>* Other names: Placebo treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary safety endpoint in this study is; safety parameters include adverse events, hypoglycemia and allergic reactions | To investigate the safety and tolerance after a repeated allogeneic infusion of Whartons Jelly Mesenchymal Stromal Cells (WJMSCs) intravenously in adult patients diagnosed with type 1 diabetes after one year following the repeated treatment. | 372 days | 
| Delta-change of C-peptide AreaUnder 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. | To study changes in insulin requirements during one year following treatment . | 372 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients insulin independent (ADA criteria) at day 372. | To study changes in insulin requirements during one year following treatment . | 372 days | 
| Number of patients with daily insulin needs <0.25U/kg at day 372. | To study changes in insulin requirements during one year following treatment . | 372 days | 
| HbA1c at day 372 | To study changes in HbA1c during one year following treatment. | 372 days | 
| Glucose variability (mean amplitude of glycaemic excursions and glycaemic lability index) duration derived from the continuous glucose monitoring system® at day 372 | To study changes in glucose levels during one year following treatment. | 372 days | 
| Delta change of levels of fasting C-peptide at day 372 when compared to test before start of treatment | To study changes in fasting C-peptide levels during one year following treatment. | 372 days | 
| Numbers of patients with peak C-peptide >0.20 nmol/l, in response to the MMTT, at day 372. | To study changes in C-peptide levels during one year following treatment. | 372 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 1 diabetes, diabetes, MSC's, Mesenchymal, Stem Cells, Stromal, Wharton´s Jelly