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

• ClinicalTrials.gov Identifier: NCT03973827
• Recruitment Status: Active, not recruiting
• First Posted: June 4, 2019
• Last Update Posted: April 3, 2023
• Sponsor: NextCell Pharma Ab
• Information provided by (Responsible Party): NextCell Pharma Ab

Tracking Information

• First Submitted Date: May 16, 2019
• First Posted Date: June 4, 2019
• Last Update Posted Date: April 3, 2023
• Actual Study Start Date: May 17, 2019
• Actual Primary Completion Date: December 10, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 30, 2023)

• The primary safety endpoint in this study is; safety parameters include adverse events, hypoglycemia and allergic reactions [ Time Frame: 372 days ]
  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.
• 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. [ Time Frame: 372 days ]
  To study changes in insulin requirements during one year following treatment .

Original Primary Outcome Measures (submitted: June 3, 2019)

• The primary safety endpoint in this study is; safety parameters include adverse events, hypoglycemia and allergic reactions [ Time Frame: 372 days ]
  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.
• 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 startof treatment. [ Time Frame: 372 days ]

Current Secondary Outcome Measures (submitted: March 30, 2023)

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

Original Secondary Outcome Measures (submitted: June 3, 2019)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Wharton´s Jelly Derived Mesenchymal Stromal Cell Repeated Treatment of Adult Patients Diagnosed With Type I Diabetes
• Official Title: 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
• 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 18 adult male patients, 18-41 years of age (inclusive at both ends) diagnosed (<3,5 years) with type 1 diabetes mellitus.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Type1diabetes

Intervention

• Drug: ProTrans
  Single infusion of 25, 100 or 200 million cells per patient.
  Other Name: Allogeneic transplantation with WJMSCs
• Drug: Placebo
  Placebo Comparator: Sham transplantation (placebo) Single infusion with albumin and dmso in sodium chloride (identical concentrations as active treatment)
  Other Name: Placebo treatment

Study Arms

• Experimental: Low dose
  3 patients receiving low dose
  Intervention: Drug: ProTrans
• Experimental: Medium dose
  3 patients receiving medium dose
  Intervention: Drug: ProTrans
• Experimental: High dose
  3 patients receiving high dose
  Intervention: Drug: ProTrans
• Sham Comparator: Control
  6 patients
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 17, 2021): 15
• Original Estimated Enrollment (submitted: June 3, 2019): 18
• Estimated Study Completion Date: October 30, 2024
• Actual Primary Completion Date: December 10, 2020 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 41 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Sweden

Administrative Information

• NCT Number: NCT03973827
• Other Study ID Numbers: ProTrans-Repeat; 2018-004158-11 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: NextCell Pharma Ab
• Original Responsible Party: Same as current
• Current Study Sponsor: NextCell Pharma Ab
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Per-Ola Carlsson, PhD; Uppsala University

• PRS Account: NextCell Pharma Ab
• Verification Date: March 2023