Clinical Study on the Safety and Efficacy of Immunophenotyped Pancreatic Endocrine Organoid Bank in Treating Patients With T3c Diabetes

NCT06991829 | Active Not Recruiting Early Phase 1 DMC

• 1 other identifier: ZSPAC-10
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

Islet cells are isolated from resected pancreatic tissue obtained from patients undergoing surgery, followed by ex vivo expansion and culture. Subsequent procedures include HLA typing, functional assessment of organoid-like structures, and biobanking. After matching for HLA, the cells are administered into patients with type 3c diabetes mellitus (T3cDM) via ultrasound-guided percutaneous transhepatic portal vein catheterization. A 52-week follow-up is conducted to evaluate the safety of the cell therapy and its clinical efficacy in glycemic control.

Conditions

Diabetes Mellitus

Keywords

type 3c diabetes mellitus; pancreatic endocrine organoids; Islet Transplantation; HLA-immunotyped

Outcome Measures

Primary Outcomes (3)

• Proportion of Participants with ≥50% Reduction in Daily Insulin Dose at Week 52 Post-Transplantation Compared to Baseline

  The percentage of participants whose daily insulin requirement is reduced by at least 50% at 52 weeks after organoid transplantation, compared to their baseline insulin dose.

  From enrollment to the end of treatment at 52 weeks post-transplantation

• Proportion of Participants with HbA1c < 7.0% at Week 52 Post-Transplantation

  The percentage of participants achieving HbA1c levels \<7.0% at 52 weeks post-transplantation, indicating improved long-term glycemic control.

  From enrollment to the end of treatment at 52 weeks post-transplantation

• Number of Participants with No Episodes of Severe Hypoglycemia Between Weeks 12 and 52 Post-Transplantation

  The number of participants who report zero episodes of severe hypoglycemia during the 12 to 52 weeks post-transplantation period.

  From Week 12 to Week 52 post-transplantation

Secondary Outcomes (9)

• Proportion of Participants with HbA1c < 7.0% at Weeks 12, 26, and 52 Post-Transplantation

  Weeks 12, 26, and 52 post-transplantation

• Proportion of Participants with ≥50% Reduction in Daily Insulin Dose at Weeks 12, 26, and 52 Post-Transplantation

  Weeks 12, 26, and 52 post-transplantation

• Proportion of Participants Achieving Insulin Independence at Weeks 26 and 52 Post-Transplantation

  Weeks 26 and 52 post-transplantation

• Proportion of Participants with Stimulated C-Peptide Peak > 0.3 ng/mL Following a Mixed Meal Tolerance Test at Weeks 12, 26, and 52

  Weeks 12, 26, and 52 post-transplantation

• Time-in-Range (TIR) at Weeks 12, 26, and 52 Post-Transplantation

  Weeks 12, 26, and 52 post-transplantation

Study Arms (1)

HLA-matched pancreatic endocrine organoids transplantation

EXPERIMENTAL

Islet cells are isolated from resected pancreatic tissue obtained from patients undergoing surgery, followed by ex vivo expansion and culture. Subsequent procedures include HLA typing, functional assessment of organoid-like structures, and biobanking. After matching for HLA, the cells are administered into patients with type 3c diabetes mellitus (T3cDM) via ultrasound-guided percutaneous transhepatic portal vein catheterization. A 52-week follow-up is conducted to evaluate the safety of the cell therapy and its clinical efficacy in glycemic control.

Procedure: HLA-matched pancreatic endocrine organoids transplantation

Interventions

HLA-matched pancreatic endocrine organoids transplantation PROCEDURE

Islet cells are isolated from resected pancreatic tissue obtained from patients undergoing surgery, followed by ex vivo expansion and culture. Subsequent procedures include HLA typing, functional assessment of organoid-like structures, and biobanking. After matching for HLA, the cells are administered into patients with type 3c diabetes mellitus (T3cDM) via ultrasound-guided percutaneous transhepatic portal vein catheterization. A 52-week follow-up is conducted to evaluate the safety of the cell therapy and its clinical efficacy in glycemic control.

HLA-matched pancreatic endocrine organoids transplantation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥18 and ≤70 years at the time of informed consent, regardless of sex; History of total pancreatectomy with baseline C-peptide levels below the lower limit of normal;
• Post-pancreatectomy hyperglycemia consistent with diagnostic criteria for T3cDM;
• Stimulated C-peptide level \< 0.3 ng/mL at 120 minutes following a mixed meal;
• HbA1c≥7.5% or TIR \< 70% despite intensified insulin therapy;
• Male participants who are sexually active and not surgically sterilized or whose partners are of childbearing potential must agree to use effective contraception and refrain from sperm donation throughout the study and for at least 6 months thereafter; female participants of childbearing potential must agree to use effective contraception for the duration of the study and for at least 6 months thereafter.
• Voluntary written informed consent and willingness to comply with the study protocol and visit schedule.

You may not qualify if:

• Known hemoglobinopathies or moderate-to-severe anemia interfering with HbA1c interpretation;
• Positive HBsAg or HBcAb with HBV DNA ≥10⁴ copies/mL or ≥2000 IU/mL; Patients with positive HBsAg and HBV DNA \<2000 IU/mL must be on antiviral therapy throughout the study. Patients with positive HBcAb and HBV DNA \<2000 IU/mL must undergo regular HBV DNA monitoring;
• Positive HCV antibody with HCV RNA≥10³IU/mL;
• Positive HIV antibody testing;
• Active syphilis infection (those with resolved infection may be included);
• Existence or suspicion of other uncontrollable or untreatable fungal, bacterial, viral or other infections;
• Uncontrolled hypertension (SBP \>160 mmHg and/or DBP \>100 mmHg despite stable antihypertensive treatment for ≥4 weeks);
• History of coagulopathy or long-term anticoagulation therapy (e.g., warfarin) or INR \>1.5 (low-dose aspirin permitted);
• Impaired liver function: AST or ALT \>3× ULN Total bilirubin \>2× ULN;
• Impaired renal function with Creatinine clearance \<45 mL/min (Cockcroft-Gault formula);
• History of end-stage heart or lung disease, or cirrhosis;
• Presence or history of any type of cancer, excluding papillary thyroid cancer cured for more than 1 year;
• Severe mental/psychological disorders, or severe cognitive impairment
• Pregnant or lactating women;
• Other situations or abnormal findings judged by the investigator as unsuitable for participating in the trial.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead
• Shanghai Newislet Therapeutics Co., Ltd.: collaborator

Study Sites (1)

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Conditions

Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

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

Model Details: A single-arm clinical trial is designed to evaluate whether transplantation of HLA-matched pancreatic endocrine organoids can effectively lower blood glucose levels in patients with diabetes following pancreatectomy. The trial employs Simon's Two-Stage Optimal Design to determine sample size, with parameters: P0 = 0.10 (null hypothesis), P1 = 0.30 (alternative hypothesis), α = 0.05, and β = 0.20. Given the lack of definitive treatments and the first-in-human nature of this intervention, 10 patients will be enrolled in the first stage. If ≥2 achieve treatment success, the trial proceeds to stage two; otherwise, it stops. In stage two, 19 more patients will be enrolled (total n=29). If ≥6 patients achieve treatment success, the therapy is considered effective; if \<6, it is considered ineffective.

Study Record Dates

• First Submitted: April 15, 2025
• First Posted: May 28, 2025
• Study Start: April 3, 2025
• Primary Completion (Estimated): April 3, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: May 28, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Throughout the entire clinical trial period
• Access Criteria: Qualified researchers who provide a methodologically sound proposal will be able to access the individual participant data (IPD) and related documents such as the study protocol and statistical analysis plan. Access will be granted through a secure data sharing platform upon request and approval by the study sponsor or a designated data access committee. All shared data will be de-identified to protect participant confidentiality.

Locations

CN (1)