Transplanting modified pancreatic islet cells to treat type 1 diabetes

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

This study is testing if transplanting specially modified pancreatic cells into the arm can help adults with long-term type 1 diabetes produce insulin again without needing strong medications to prevent rejection.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 2 (estimated)
• Ages: 30 Years to 45 Years
• Sex: All
• Sponsor: Uppsala University Hospital (Academic / other)
• Locations: 1 site (Uppsala)
• Trial ID: NCT06239636 on ClinicalTrials.gov

What this trial studies

This study investigates the safety of transplanting genetically modified Langerhans islet cells into the forearm muscle of adults with longstanding type 1 diabetes. The aim is to determine if these cells can help restore insulin production without the need for immunosuppressive medications. Participants will undergo frequent follow-up visits for a year, including medical examinations, blood tests, and MRI scans to monitor safety and insulin-producing cell function. The study involves a single group of participants receiving the treatment, allowing for a focused assessment of outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults diagnosed with type 1 diabetes for at least five years, who are actively managing their condition.

Not a fit: Patients who do not have a diagnosis of type 1 diabetes or those who have not been managing their diabetes intensively may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option for type 1 diabetes that reduces reliance on insulin therapy.

How similar studies have performed: While similar approaches have been explored, this specific method of using genetically modified islet cells is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Signed informed consent for participation in the study
2. 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.
3. 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.
4. C-peptide negative (C-peptide \< 0.01 nmol/l) in response to a mixed meal tolerance test (MMTT)
5. Positive for antibodies to either GAD or IA2 at screening
6. 30-45 years of age at time of enrollment
7. HbA1c ≥70 mmol/mol
8. Exogenous insulin needs \< 1 IU/kg
9. Body weight \<80 kg
10. Female subjects of child-bearing potential must agree to using adequate contraception until one year after the administration of UP421, as outlined in

https://www.hma.eu/fileadmin/dateien/Human\_Medicines/01-About\_HMA/Working\_Groups/CTFG/2014\_09\_HMA\_CTFG\_Contraception.pdf

A woman is considered of childbearing potential if she is not surgically sterile or isles than 1 year since last menstrual period.

Adequate contraception is as follows:

1. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal)
2. progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable)
3. intrauterine device (IUD)
4. intrauterine hormone-releasing system (IUS)
5. bilateral tubal occlusion f) vasectomised partner g) sexual abstinence Male subjects must not intend to procreate until one year after the administration of UP241.

   Males must be willing to use effective measures of contraception (condoms) during the whole trial period.

   Exclusion Criteria:

   Any previous organ transplantation;

   2\. Any systemic immunosuppressive medication for any other disease;

   3\. Any history of malignancy;

   4\. Use of any investigational agent(s) within 4 weeks of enrollment;

   5\. Use of any anti-diabetic medication, other than insulin, within 4 weeks of enrollment;

   6\. Active infections including Tuberculosis, HIV, HBV and HCV;

   7\. Liver function test value for AST, ALT, GGT or ALP exceeding the respective reference interval for the clinical assay at Uppsala university hospital;

   8\. Serological evidence of infection with HTLVI or HTLVII;

   9\. Pregnancy, nursing, intention for pregnancy;

   10\. Chronic kidney disease grade 3 or worse (GFR\<60 ml/min as estimated by creatine measurement) ;

   11\. Medical history of cardiac disease, or symptoms at screening consistent with cardiac disease;

   12\. HLA immunization;

   13\. MIC A/B immunization;

   14\. Known autoimmune disease other than type I diabetes (e.g. Hashimoto disease);

   15\. Administration of live attenuated vaccines \<6 months before transplant;

   16\. Islet antibodies where GADA \>2000 IE/ml or IA2A \>4000 IE/ml, or positive for ZnT8 auto-antibodies;

   17\. Untreated proliferative diabetic retinopathy;

   18\. Major ongoing psychiatric illness which the Principal Investigator judges increases the risk of noncompliance or does not allow safe participation in the study;

   19\. Ongoing substance abuse, drug or alcohol; or recent history of treatment noncompliance;

   20\. Known hypersensitivity to ciprofloxacin, gentamicin, or amphotericin (since these are used in the manufacturing process of UP421);

   21\. Any other condition that in the opinion of the Principal Investigator does not allow safe participation in the study.

Where this trial is running

Uppsala

• Uppsala University Hospital — Uppsala, Sweden (Recruiting)

Study contacts

• Principal investigator: Per-Ola Carlsson, MD, PhD — Uppsala University Hospital
• Study coordinator: Per-Ola Carlsson, MD, PhD

Conditions Type1diabetes