First-in-human Safety Study of Hypoimmune Pancreatic Islet Transplantation in Adult Subjects With Type 1 Diabetes

NCT06239636 | Recruiting Early Phase 1 DMC

• 2 other identifiers: UP421-ET1D2023-507988-19-00
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The current study tests the hypothesis whether genetically modified Langerhans islet cells containing insulin-producing cells from a deceased organ donor can

1. 1.be transplanted safely and
2. 2.help to regain insulin production in individuals with type 1 diabetes without need in simultaneous treatment with immunosuppressive medicines.

Conditions

Type1diabetes

Outcome Measures

Primary Outcomes (1)

• Safety as assessed by number of treatment related adverse events accoridng to CTCAE v 5.0

  Number of treatment related adverse events as assessed by CTCAE v5.0

  12 months

Secondary Outcomes (10)

• Immune evasion of implanted cells, as evaluated in systemic peripheral blood.

  12 months

• Presence of peak C-peptide >0.01 nmol/l in response to a mixed meal tolerance test

  12 months

• Presence of non-fasting C-peptide concentrations >0.01 nmol/l.

  12 months

• Presence of peak C-peptide >0.20 nmol/l in response to a mixed meal tolerance test

  12 months

• Survival of implanted cells as assessed by Magnetic resonance imaging

  12 months

Study Arms (1)

UP421 transplantation

EXPERIMENTAL

Intramuscular transplantation of study product UP421

Biological: UP421

Interventions

UP421 BIOLOGICAL

Intramuscular transplantation with the ATMP UP421 composed of genetically modified human pancreatic islet cells

UP421 transplantation

Eligibility Criteria

• Age: 30 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent for participation in the study
• Diagnosis of type 1 diabetes mellitus (T1D);
• i) for ≥ 5 years and
• ii) diagnosed before the age of 18 years and
• iii) at least one or more HbA1c documented in the subject's medical journal or Swedish National Diabetes Registry during the last five-year period must be
• ≥70 mmol/mol.
• The subject must be involved in intensive diabetes management defined as self-monitoring of subcutaneous glucose level by continuous glucose monitoring or by
• intermittent scanning glucose monitoring no less than a mean of three times per day averaged over each week and by the administration of three or more insulin
• injections per day or insulin pump therapy. This management must be under the direction of an M.D specialized in endocrinology and diabetology with support of
• a diabetes nurse at a specialist clinic for Endocrinology and Diabetology or Internal Medicine during the 12 months prior to study enrolment.
• C-peptide negative (C-peptide \< 0.01 nmol/l) in response to a mixed meal tolerance test (MMTT)
• Positive for antibodies to either GAD or IA2 at screening
• years of age at time of enrollment
• HbA1c ≥70 mmol/mol
• Exogenous insulin needs \< 1 IU/kg

You may not qualify if:

• Any previous organ transplantation;
• \. Any systemic immunosuppressive medication for any other disease;
• \. Any history of malignancy;
• \. Use of any investigational agent(s) within 4 weeks of enrollment;
• \. Use of any anti-diabetic medication, other than insulin, within 4 weeks of enrollment;
• \. Active infections including Tuberculosis, HIV, HBV and HCV;
• \. Liver function test value for AST, ALT, GGT or ALP exceeding the respective reference interval for the clinical assay at Uppsala university hospital;
• \. Serological evidence of infection with HTLVI or HTLVII;
• \. Pregnancy, nursing, intention for pregnancy;
• \. Chronic kidney disease grade 3 or worse (GFR\<60 ml/min as estimated by creatine measurement) ;
• \. Medical history of cardiac disease, or symptoms at screening consistent with cardiac disease;
• \. HLA immunization;
• \. MIC A/B immunization;
• \. Known autoimmune disease other than type I diabetes (e.g. Hashimoto disease);
• \. Administration of live attenuated vaccines \<6 months before transplant;

Sponsors & Collaborators

• Per-Ola Carlsson: lead
• Sana Biotechnology: collaborator

Study Sites (1)

Uppsala University Hospital

Uppsala, 75185, Sweden

RECRUITING

Related Publications (1)

• Carlsson PO, Hu X, Scholz H, Ingvast S, Lundgren T, Scholz T, Eriksson O, Liss P, Yu D, Deuse T, Korsgren O, Schrepfer S. Survival of Transplanted Allogeneic Beta Cells with No Immunosuppression. N Engl J Med. 2025 Sep 4;393(9):887-894. doi: 10.1056/NEJMoa2503822. Epub 2025 Aug 4.

  PMID: 40757665 DERIVED

Study Officials

• Per-Ola Carlsson, MD, PhD

  Uppsala University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Per-Ola Carlsson, MD, PhD

CONTACT

+46 18 4710000; per-ola.carlsson@mcb.uu.se

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Senior consultant

Study Record Dates

• First Submitted: January 22, 2024
• First Posted: February 2, 2024
• Study Start: March 8, 2024
• Primary Completion: May 1, 2025
• Study Completion: June 1, 2025
• Last Updated: December 11, 2024

Record last verified: 2024-12

Locations

SE (1)