Clinical trial NCT03973827: Wharton´s Jelly Derived Mesenchymal Stromal Cell Repeated Treatment of Adult Patients Diagnosed with Type I Diabetes
Official title: An Open Label, Parallel Single Centre Trial of Wharton's Jelly Derived Allogeneic Mesenchymal Stromal Cells Repeated Treatment to Preserve Endogenous Insulin Production in Adult Patients Diagnosed with Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Type1diabetes
Keywords: type 1 diabetes
diabetes
MSC's
Mesenchymal
Stem Cells
Stromal
Wharton´s Jelly
Lead sponsor: NextCell Pharma Ab
Sponsor class: INDUSTRY
First posted: 2019-06-04
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Maximum age (years): 41
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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 15 adult male patients, 18-41 years of age (inclusive at both ends) diagnosed (\<3,5 years) with type 1 diabetes mellitus.

Eligibility criteria: 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.

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.
5. Patients with uncontrolled hypertension (≥160/105 mmHg).
6. Patients with active on-going infections.
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).- This criterion is only applicable to patients which receive study drug.

Primary outcomes:
measure: The primary endpoint in this study is; safety parameters include adverse events and hypoglycemia, allergic reactions, ophthalmologic examination, ECG, vital signs, laboratory assessments.
timeFrame: 372 days
measure: 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 when compared to control patients.
timeFrame: 372 days
Secondary outcomes:
measure: Number of patients insulin independent (ADA criteria) at day 372.
timeFrame: 372 days
measure: Number of patients with daily insulin needs <0.25U/kg at day 372.
timeFrame: 372 days
measure: Insulin requirement/kg BW at day 372. HbA1c at day 372.
timeFrame: 372 days
measure: HbA1c at day 372
timeFrame: 372 days
measure: Glucose variability (mean amplitude of glycaemic excursions and glycaemic lability index) duration derived from the continuous glucose monitoring system® at day 372
timeFrame: 372 days
measure: Delta change of levels of fasting C-peptide at day 372 when compared to test before start of treatment
timeFrame: 372 days
measure: Numbers of patients with peak C-peptide >0.20 nmol/l, in response to the MMTT, at day 372.
timeFrame: 372 days
measure: To study changes during one year following treatment in: -Insulin doses -HbA1c -Glucose variability -Diabetes Treatment Satisfaction
timeFrame: 372 days
measure: To study changes in insulin requirements during one year following treatment
timeFrame: 372 days
Other outcomes:
Locations:
city: Huddinge
country: Sweden
facility: Karolinska Trial Alliance, Fas 1 enheten, Karolinska Universitetssjukhuset Huddinge
Study officials:
affiliation: Uppsala University
name: Per-Ola Carlsson, PhD
role: PRINCIPAL_INVESTIGATOR
References: