Clinical trial NCT06575426: A Study to Investigate Safety and Effectiveness of Porcine Pancreatic Cells (OPF-310) in Patients With Type 1 Diabetes Mellitus
Official title: A Phase I/IIa, Single Site, Open-Label, Ascending Dose Study to Evaluate the Safety and Efficacy of OPF-310 [Encapsulated Porcine Islet Cells for Xenotransplantation] in Subjects With Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Diabetes Mellitus, Type 1
Hypoglycemia
Islet Cell Transplantation
Keywords: Diabetes Mellitus
Diabetes Mellitus, Type1
T1DM
Hypoglycemia
islet cell transplantation
pig islet cell transplantation
Lead sponsor: Otsuka Pharmaceutical Factory, Inc.
Sponsor class: INDUSTRY
First posted: 2024-08-28
Enrollment: 13
Sex: ALL
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A Phase I/IIa, Single site, Open-Label, Ascending Dose Study
Primary purpose: TREATMENT

Brief summary: This study is First In Human study for Encapsulated Porcine Islet Cells for Xenotransplantation (OPF-310). The purpose of this study to assess the safety, tolerability, and efficacy of OPF-310 transplantation and to define the recommended Phase 2 dose (RP2D) in adult subjects with unstable Type 1 Diabetes Mellitus (T1DM) and a level 3 (severe) hypoglycemic episode at least three times within the 1 year prior to enrollment despite treatment with a closed loop system (CLS) for at least 6 months.


Eligibility criteria: Inclusion Criteria:

1. Subject must be aged 35 to 65 years of age inclusive, at the time of signing the informed consent.
2. Subject has an established diagnosis of type 1 diabetes mellitus (T1DM)(in accordance with the American Diabetes Association's criteria), with a minimum duration since diagnosis of 5 years.
3. If one of the following criteria (either a or b) applies:

   1. Subject has unstable T1DM, not achieving adequate control after receiving CLS (CGM:Dexcom G6, insulin pump: Omnipod® 5 or t:slim X2) under care of a qualified diabetes team for at least 6 months prior to enrollment.
   2. Subject has unstable T1DM, not achieving adequate control after receiving CLS (CGM:Dexcom G7, insulin pump: Omnipod® 5, t:slim X2, iLet Bionic Pancreas or The Tandem Mobi System) under care of a qualified diabetes team for at least 6 months prior to enrollment.
4. If one of the following criteria (either a, b or c) applies:

   1. Subject has had a Level 3 (severe) hypoglycemic episode (defined as having cognitive impairment requiring external assistance for recovery) at least three times within the 1 year prior to enrollment recorded in the medical record or patient log.
   2. Subject has had a Level 3 (severe) hypoglycemic episode at least once within the 1 year prior to enrollment and demonstrates a Clarke Score ≥4, assessed by trained study personnel. The SHE(s) and Clarke Score must be recorded in the medical record or patient log.
   3. Subject has had TBR \>1% at glucose levels below 70mg/dL and demonstrates a Clarke Score≥4, assessed by trained study personnel. TBR data used for screening and Clarke score must be recorded in the medical record or patient log.
5. Subject has C-peptide \<0.3 ng/mL following a mixed meal tolerance test or undetectable fasting C-peptide.
6. Hemoglobin A1C (HbA1c) ≥ 7.5 and ≤ 9.0
7. Contraceptive use must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
8. Subject who can agree to cooperate with lifetime follow-up after transplantation.
9. Subject is capable of providing signed informed consent

Exclusion Criteria:

1. Previous history of insulin resistance (defined as an average insulin dose requirement ≥ 0.8 unit/kg/day for 1 week prior to enrollment).
2. Subject has latent autoimmune diabetes in adults (LADA), ketosis-prone (Flatbush) diabetes, or maturity onset diabetes of the young (MODY).
3. CRP ≥ 10 mg/L.
4. Clinically unstable thyroid disease (thyroid stimulating hormone (TSH)\< the lower limit of the normal range of TSH at the site.) Patients with subclinical hyperthyroidism can be rescreened once TSH levels normalize due to treatment or other factors. In addition, patients with transiently abnormal TSH levels may undergo rescreening only once during the screening period.
5. History of malignancies within the past 5 years, excluding basal and squamous cell carcinoma
6. Positive serologies or nucleic acid testing for human immunodeficiency virus (HIV), hepatitis C, and hepatitis B.
7. Active or untreated proliferative diabetic retinopathy. Subjects may be rescreened once they are successfully treated.
8. Serious comorbid conditions that are likely to affect participation in the study, including:

   1. Within the last 12 months, peripheral vascular disease with previous amputation.
   2. History of New York Heart Association (NYHA) class II, III or IV congestive heart failure (CHF) and/or chronic atrial fibrillation.
   3. Chronic obstructive pulmonary disease (COPD) or asthma with previous hospitalization for decompensation; a requirement for mechanical ventilation at any stage; or long- term treatment with oral corticosteroids.
   4. Macroalbuminuria (\> 300 mg albumin/gm creatinine).
   5. Estimated glomerular filtration rate (eGFR) cut-off of \< 30 ml/min for all per Kidney Disease Improving Global Outcomes (KDOQI) and Kidney Disease Outcomes Quality Initiative (KDIGO) consensus.
9. Use of warfarin or other anticoagulant therapy (except aspirin), or prothrombin time and international normalized ratio (PT-INR) \> 1.5
10. Adrenal insufficiency being treated with corticosteroids
11. Previous pan-peritonitis
12. Previous cardiovascular or cerebrovascular disease
13. Patients with hematopoietic stem cell abnormalities (e.g., aplastic anemia, myelodysplastic syndrome)
14. Patients who received a blood transfusion in the previous 90 days, are anticipated to undergo surgery during the 1-year study period that may require transfusion, or have donated blood within the previous 90 days.
15. Previous receipt of an organ, skin allograft, or other tissue transplant from an allogeneic human or animal donor.
16. Treatment with immunosuppressive medication.
17. Previous abdominal surgery, excluding uncomplicated appendectomy, cholecystectomy, exploratory laparoscopy and hernia repair performed prior to 12 weeks prior to enrollment.
18. Treatment with any non-insulin hypoglycemic medication not intended to be used as an adjunct to insulin therapy.
19. Treatment with acetaminophen or hydroxycarbamide.
20. Use of any investigational products within 12 weeks of enrollment (before entering run-in) or 5 half-lives of the investigational product, whichever is greater.
21. Subject has history of allergy to antibiotics (Amphotericin B, Cefazolin, Ciprofloxacin, Gentamicin), which are used during manufacture of OPF-310.
22. Previous history of insulin allergy (including porcine insulin), pork product allergy or alginate/seaweed allergy.
23. Panel reactive antibodies (PRA) \> 80 %.
24. Active drug, substance or alcohol addiction.
25. Body mass index (BMI) \>27 kg/m2.
26. Any other condition that, in the opinion of the Investigator, may interfere with adherence to the study protocol, including dementia, psychiatric disorder, medical condition, or a history of non-adherence to appointments or treatments

Primary outcomes:
measure: Percentage of Subjects Reaching the Efficacy Goal
timeFrame: One year after transplant
Secondary outcomes:
measure: Percentage of subjects with reduction in HbA1c more than 1 %
timeFrame: 12 week, 24 week 52 weeks after transplant
measure: Percentage reduction in nocturnal hypoglycemic event rate
timeFrame: 12 week, 24 week 52 weeks after transplant
measure: Percentage improvement in time below range (<70 mg/dl) by continuous glucose monitoring (CGM)
timeFrame: 12 week, 24 week 52 weeks after transplant
measure: Percentage improvement in time in range (70-180 mg/dl) by CGM
timeFrame: 12 week, 24 week 52 weeks after transplant
measure: Percentage improvement in time above range (>180 mg/dl) by CGM
timeFrame: 12 week, 24 week 52 weeks after transplant
measure: Change in mean amplitude of glycemic excursion (MAGE) by CGM.
timeFrame: 12 week, 24 week 52 weeks after transplant
measure: Percentage reduction in daily average of insulin use
timeFrame: 12 week, 24 week 52 weeks after transplant
measure: Percentage of subjects with an HbA1c < 7.0 % assessed at 52 weeks post-transplant
timeFrame: One year after transplant
measure: Percentage of subjects with an HbA1c ≤ 6.5 % assessed at 52 weeks post-transplant
timeFrame: One year after transplant
measure: Percentage of subjects with positive porcine C-peptide qualitatively assessed by digital ELISA assay
timeFrame: One year after transplant
measure: Values of porcine C-peptide during mixed meal tolerance test (MMTT) and Intravenous Glucose Tolerance Test (IVGTT) at each measuring point
timeFrame: For one year after transplant
measure: Values of human C-peptide during mixed meal tolerance test (MMTT) and Intravenous Glucose Tolerance Test (IVGTT) at each measuring point
timeFrame: For one year after transplant
measure: Values of Glucose during mixed meal tolerance test (MMTT) and Intravenous Glucose Tolerance Test (IVGTT) at each measuring point
timeFrame: For one year after transplant
measure: Psychological impact as assessed by the Diabetes Distress Scale (DDS) at each measuring point.
timeFrame: For one year after transplant
measure: Psychological impact as assessed by the Hypoglycemic Fear Survey (HFS) at each measuring point.
timeFrame: For one year after transplant
measure: Percentage of subjects with improved awareness of hypoglycemia, as defined by a change in Clarke questionnaire score from ≥ 4 to < 4.
timeFrame: For one year after transplant
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois Hospital &Health Scences System
state: Illinois
Study officials:
References: