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Type1diabetesEarly Phase 1NCT06239636

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

A Early Phase 1 study testing UP421 in people with Type1diabetes, run by Per-Ola Carlsson at 1 site in Sweden.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The current study tests the hypothesis whether genetically modified Langerhans islet cells containing insulin-producing cells from a deceased organ donor can 1. be transplanted safely and 2. Read more about this study

Who is it for?
Ages 30 to 45 years
Conditions the study is for
Type1diabetes
What is being tested?
UP421
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteSweden
Study dates
8 Mar 2024to Jun 2025
Phase
Early Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 to 45 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Signed informed consent for participation in the study
  • Diagnosis of type 1 diabetes mellitus (T1D);
  • for ≥ 5 years and
  • diagnosed before the age of 18 years and
  • 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.
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  • 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
  • 30-45 years of age at time of enrollment
  • HbA1c ≥70 mmol/mol
  • Exogenous insulin needs < 1 IU/kg
  • Body weight <80 kg
  • 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/HumanMedicines/01-AboutHMA/WorkingGroups/CTFG/201409HMACTFGContraception.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:
  • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal)
  • progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable)
  • intrauterine device (IUD)
  • intrauterine hormone-releasing system (IUS)
  • 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.

Who cannot join

  • 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;
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  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Per-Ola Carlsson, MD, PhD contact

+46 18 4710000 ext. 4425

per-ola.carlsson@mcb.uu.se

Sweden1 site, 1 recruiting

  • Uppsala University Hospital

    Uppsala, 75185

    Per-Ola Carlsson, MD, PhD, +4618471 ext. 4425, per-ola.carlsson@mcb.uu.se

    Recruiting

Other trials in Sweden

About this study

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

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

The study is an open, one-armed study where adult subjects with longstanding type 1 diabetes will receive transplantation of Langerhans islet cells (25 000 000-80 000 000) into forearm muscle. Both subjects receive active treatment. Safety is monitored with frquent follow-up visits over a year, including medical examinations, blood tests and MRI scans. Insluin producing cell function is monitored with blood samples and continuous glucose measurement.

Main objective is to to investigate the safety of an intramuscular transplantation of genetically modified allogeneic human islets (study product UP421) in adult subjects diagnosed with type 1 diabetes.

Secondary objectives are to study changes in beta-cell function, metabolic control and immunological response to pancreatic islets during the first year following treatment.

Conditions
Type1diabetes
Being tested
UP421

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • UP421Biological

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

Study groups in NCT06239636
Study groupRoleWhat they receive
UP421 transplantationExperimentalIntramuscular transplantation of study product UP421
Receives: Biological: UP421

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 12 months

Secondary outcomes (10)

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

    Assessed at 0 (before tx), 2, 4, 8, 12, 18, 26 and 52 weeks post-transplantation

    Measured: 12 months

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

    Assessed at 4, 8, 12, 18, 26 and 52 weeks post-transplantation

    Measured: 12 months

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

    Assessed at 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 and 52 weeks post-transplantation

    Measured: 12 months

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

    Assessed at 4, 8, 12, 26 and 52 weeks post-transplantation

    Measured: 12 months

  5. Survival of implanted cells as assessed by Magnetic resonance imaging

    Assessed within 48 h after transplantation and 2, 4, 6, 8, 12, 26 and 52 weeks post-transplantation

    Measured: 12 months

  6. C-peptide AUC in response to a mixed meal tolerance test

    Assessed at 4, 8, 12, 18, 26 and 52 weeks post-transplantation

    Measured: 12 months

  7. Delta changes in insulin requirement/kg BW

    Assessed at 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 and 52 weeks transplantation when compared to before transplantation

    Measured: 12 months

  8. Delta changes in HbA1c

    Assessed at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 26 and 52 weeks post-transplantation when compared to before transplantation

    Measured: 12 months

  9. Delta changes in glucose variability derived from a continuous glucose monitoring system

    Assessed at 4, 8, 12, 18, 26 and 52 weeks post-transplantation when compared to before transplantation

    Measured: 12 months

  10. Score in diabetes treatment satisfaction questionnaire

    Assesssed at 4, 8, 12, 18, 26 and 52 weeks post-transplantation when compared to before transplantation

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Feb 2024
  2. Study start8 Mar 2024
  3. Primary completionMay 2025 (estimated)
  4. Study completionJun 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06239636
Sponsor's protocol ID
UP421-ET1D
Other IDs
2023-507988-19-00, 2023
Status last verified
Dec 2024
First submitted
22 Jan 2024
Last updated
11 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 40757665

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing UP421 in people with Type1diabetes, run by Per-Ola Carlsson at 1 site in Sweden.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 11 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Per-Ola Carlsson, MD, PhD (+46 18 4710000 ext. 4425, per-ola.carlsson@mcb.uu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety as assessed by number of treatment related adverse events accoridng to CTCAE v 5.0 (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06239636, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2024; AzTrials last refreshed its copy on 8 Nov 2026.

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