Phase 1/1b study to evaluate the safety of OZTx-410 in individuals with type 1 diabetes eligible for pancreatic islet transplantation

JRCT ID: jRCT2053240146

Registered date:03/10/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Type 1 Diabetes
• Date of first enrollment: 01/01/2025
• Target sample size: 3
• Study type: Interventional

Intervention(s)

The CGM device will be worn from the time of obtaining consent for participation in the clinical trial until the end of the observation period.
OZTx-410 will be implanted subcutaneously under general anesthesia.

Outcome(s)

• Primary Outcome: Types, severity, seriousness, and frequency of adverse events (AEs) that occurred within one year after OZTx-410 transplantation.
• Secondary Outcome: Safety evaluation (types, severity, seriousness, and frequency of AEs that occurred within 5 years after OZTx-410 transplantation, and presence or absence of abnormal findings on chest and abdominal CT, chest X-ray, and abdominal ultrasound) and preliminary efficacy evaluation.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 65age old
• Gender: Both

Include criteria

At the time of the first registration:
1. Subjects diagnosed with type 1 diabetes more than 5 years before signing the informed consent form.
2. Male and female subjects between the ages of 20 and 65 at the time of signing the informed consent form.
3. Subjects who signed the informed consent form prior to undergoing any procedure or treatment related to this clinical trial.
4. Subjects whose insulin dependency has persisted for more than 5 years at the time of signing the informed consent form.
5. Subjects who have been undergoing intensive insulin therapy for diabetes for at least 1 year at the time of signing the informed consent form.
6. Subjects who have experienced at least one severe hypoglycemic episode or had blood glucose levels below 54 mg/dL within the 12 months prior to signing the informed consent form.

At the time of the second registration:
1. Subjects whose endogenous insulin secretion has been depleted.

Exclude criteria

At the time of the first registration:
1. Subjects with a body weight of 80 kg or more, or a body mass index (BMI) of 30 kg/m^2 or more.
2. Subjects whose average hemoglobin A1c (HbA1c) level from at least the two most recent measurements within the 12 months prior to signing the informed consent form is 10.0% or higher.
3. Subjects with systolic blood pressure (SBP) exceeding 160 mmHg or diastolic blood pressure (DBP) exceeding 100 mmHg.
4. Subjects who have contracted invasive aspergillosis within 1 year prior to signing the informed consent form.
5. Subjects with severe concomitant heart disease.
6. Subjects receiving chronic systemic steroid therapy at the time of signing the informed consent form.
7. Subjects who have been administered antidiabetic drugs other than insulin within 4 weeks prior to the first registration.
8. Subjects with a history of islet transplantation, organ transplantation, or cell transplantation.
9. Subjects using immunosuppressive drugs at the time of signing the informed consent form.
10. Subjects with a history of hypersensitivity to ingredients used in the manufacturing process of the investigational product.
11. Subjects with known hypersensitivity or contraindications to the non-cellular components or excipients of the investigational product.
12. Subjects who have been administered an investigational product, investigational device, or investigational drug (including those used in clinical research and post-marketing clinical trials) within 4 weeks prior to signing the informed consent form, or within 4 weeks (or 5 times the half-life of the drug, whichever is shorter) of the investigational drug.
13. Subjects who received a live vaccine within 2 weeks prior to signing the informed consent form.
14. Female subjects who are breastfeeding or planning to conceive during the trial period.
15. Female subjects of childbearing potential who do not agree to undergo or are unwilling to undergo pregnancy testing during the trial period.
16. Subjects who do not agree to use effective contraception, as defined by the trial protocol, from the time of consent until the final observation date (or discontinuation date) or for 6 weeks after discontinuing oral mycophenolate mofetil, whichever is longer.
17. Subjects deemed inappropriate for participation in the trial by the principal investigator or sub-investigator.

At the time of the second registration:
1. Subjects with a body weight of 80 kg or more, or a BMI of 30 kg/m^2 or more.
2. Subjects whose average weekly insulin requirement is 0.8 U/kg/day or 55 U/day or more.
3. Subjects with untreated or unstable pre-proliferative or proliferative diabetic retinopathy.
4. Subjects with systolic blood pressure (SBP) exceeding 160 mmHg or diastolic blood pressure (DBP) exceeding 100 mmHg.
5. Subjects with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73m^2 or lower, or with urinary protein levels of 1 g/g Cr or higher.
6. Subjects with active infections.
7. Subjects whose Epstein-Barr virus (EBV) VCA-IgG antibody test result is negative.
8. Subjects who have dental caries identified during the screening dental examination and will not have completed treatment by the time of the second registration.
9. Subjects with malignant tumors.
10. Subjects with alcohol or drug dependence.
11. Subjects who meet one or more of the following criteria: Hemoglobin level below 10.0 g/dL, Lymphocyte count below 700/uL, Neutrophil count below 1,500/uL, Platelet count below 100,000/uL.
12. Subjects with blood coagulation disorders.
13. Subjects with severe liver dysfunction.
14. Subjects with lipid metabolism disorders resistant to medical treatment.
15. Subjects with severe comorbid heart disease.
16. Subjects with symptomatic gallstone disease.
17. Subjects with acute or chronic pancreatitis.
18. Subjects with symptomatic peptic ulcer disease.
19. Subjects with severe frequent diarrhea, vomiting, or gastrointestinal disorders that may potentially interfere with the absorption of oral medications.
20. Subjects with active diabetic foot ulcers or gangrene.
21. Subjects with a positive intradermal collagen test result.
22. Female subjects who are pregnant.
23. Subjects deemed unsuitable for participation in the study by the principal investigator or sub-investigator.

Related Information

• Primary Sponsor: Yabe Daisuke
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development,Orizuru Therapeutics, Inc.