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

NCT ID: NCT03406585

Last Updated: 2023-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-28
• Study Completion Date: 2020-09-04

Brief Summary

To investigate the safety and tolerance after allogeneic infusion of WJMSCs intravenously in adult patients diagnosed with type 1 diabetes.

Detailed Description

This is a combined phase I and phase II study, where the first part is an open, dose escalating study consisting of 9 male patients, 18-40 years of age. The second part is a randomized, double-blinded, placebo-controlled, phase I/II study in parallel design comparing allogeneic WJMSC treatment to placebo in adult patients diagnosed with type 1 diabetes. Besides safety, preservation of endogenous insulin production (measured as C-peptide concentrations) together with metabolic control, diabetes treatment satisfaction and immunological profile will be assessed.

A total number of 24 patients will be enrolled in the study and followed for one year after WJMSC/placebo treatment. Patients 18-40 years of age, both male and female, diagnosed for type 1 diabetes will be eligible. Providing informed consent and fulfillment of inclusion criteria and no exclusion criteria, they will within two years of diagnosis be randomized.

Conditions

Type1 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Allogeneic transplantation with WJMSCs

Single infusion of 200 million cells per patient.

Group Type: EXPERIMENTAL

ProTrans: Allogeneic transplantation with WJMSCs

Intervention Type: DRUG

The drug is a cell suspension with allogeneic mesenchymal stromal cells derived from umbilical cord tissue.

Sham transplantation (placebo)

Single infusion with albumin and dmso in sodium chloride (identical concentrations as active treatment)

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: DRUG

Placebo treatment

Interventions

ProTrans: Allogeneic transplantation with WJMSCs

The drug is a cell suspension with allogeneic mesenchymal stromal cells derived from umbilical cord tissue.

Intervention Type: DRUG

Placebos

Placebo treatment

Intervention Type: DRUG

Other Intervention Names

Protrans; Placebo

Eligibility Criteria

Inclusion Criteria

1. Written informed consent for participation of the study, given before undergoing any study-specific procedures

2. Clinical history compatible with type 1 diabetes diagnosed less than 2 years before enrolment

3. In the first part of the study patients 1-9 only male patients between 18-40 years of age will be included. In the second part of the study, patients 10-24, both male and female patients 18 to 40 years of age (inclusive at both ends) will be included.

4. Mentally stable and, in the opinion of the investigator, able to comply with the procedures of the study protocol

5. Fasting plasma C-peptide concentration >0.12 nmol/L.

6. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, if they are using effective methods of contraception during the study. Acceptable birth control methods are those with a failure rate of less than 1% per year when used consistently and correctly. Such methods include (in "Recommendations related to contraception and pregnancy testing in clinical trials", supplied from www.hma.eu/):

1. Combined (estrogen and progestogen containing hormonal contraception associated with inhibition of ovulation.

• oral
• intravaginal
• transdermal

2. progestogen-only hormonal contracption associated with inhibition of ovulation

• oral
• injectable
• implantable

3. intrauterine device (IUD)

4. intrauterine hormone-releasing system (IUS)

5. bilateral tubal occlusion

6. total abstinence or vasectomized partner.

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. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.

12. Patients with known, or previous, malignancy.

13. Taking oral anti-diabetic therapies or any other concomitant medication which may interfere with glucose regulation other than insulin.

14. Patients with GFR <80 ml/min/1.73 m2 body surface.

15. Patients with proliferative retinopathy.

16. Patient with any condition or any circumstance that in the opinion of the investigator would make it unsafe to undergo treatment with MSC.

17. Known hypersensitivity against any excipients, i.e. dimethyl sulfoxide (DMSO).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

NextCell Pharma Ab

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Per-Ola Carlsson, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

NextCell Pharma

Locations

Karolinska Trial Alliance, Fas 1 enheten, Karolinska Universitetssjukhuset Huddinge

Stockholm, , Sweden

Countries

Sweden

References

Carlsson PO, Espes D, Sisay S, Davies LC, Smith CIE, Svahn MG. Umbilical cord-derived mesenchymal stromal cells preserve endogenous insulin production in type 1 diabetes: a Phase I/II randomised double-blind placebo-controlled trial. Diabetologia. 2023 Aug;66(8):1431-1441. doi: 10.1007/s00125-023-05934-3. Epub 2023 May 24.

Reference Type: DERIVED

PMID: 37221247 (View on PubMed)

Other Identifiers

2017-002766-50

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ProTrans-T1D

Identifier Type: -

Identifier Source: org_study_id