Safety and Efficacy of CELZ-201 in Patients With Recent Onset Type 1 Diabetes (CREATE-1)

Clinical Trial to Evaluate the Safety and Efficacy of CELZ-201 in Patients With Recent Onset Type 1 Diabetes (CREATE-1)

The brief purpose of this research study is to learn about the safety and efficacy of intra-arterial administration of CELZ-201 in patients with newly diagnosed Type 1 Diabetes Mellitus (T1D).

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 1; Type 1 Diabetes
• Intervention / Treatment: Biological: CELZ-201 Administration; Other: Control Group

Detailed Description

The proposed study is a Phase I/IIa randomized, controlled clinical trial to evaluate CELZ-201 therapy as an intervention for the treatment of recent onset Type 1 Diabetes. The objective is to determine the safety and efficacy of CELZ-201 administration, based on the timing and dose of CELZ-201 treatment. Subjects who meet eligibility criteria will be randomized to treatment or control groups, in a 2:1 ratio. Subjects in the Group I (Treatment Group, n=12) will receive standard of care for type 1 diabetes and CELZ-201 within 1 month from enrollment (within 180 days of diagnosis). Subjects in Group II (Control Arm, n=6) and will receive enhanced standard of care for type 1 diabetes.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Creative Medical Technology; Phone Number: (702) 588-1890; Email: clinicaltrials@creativemedicaltechnology.com

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • Diabetes Research Institute, University of Miami Miller School of Medicine
      • Principal Investigator: Camillo Ricordi, MD
      • Sub-Investigator: Rodolfo Alejandro, MD
      • Contact: Camillo Ricordi, MD; Phone Number: 305-243-5321

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject must be able to understand and provide signed informed consent.
2. Males and females, 18-35 years of age.
3. Diagnosis of T1D within 180 days, with stimulated C-peptide peak level >0.6 ng/mL as assessed by 4-hour MMTT at the time of Visit 0 (screening).
4. Diagnosed with T1D, according to ADA standard criteria, and confirmed by positivity to at least two islet autoantibodies, GAD65, IA-2, or ZnT8.
5. Mentally stable and able to comply with the procedures of the study protocol
6. Subjects must be willing to comply with "standard-of-care" diabetes management.
7. Subjects with eGFR >80 ml/min/1.73m2
8. Female subjects of childbearing potential must have a negative pregnancy test upon study entry.
9. Female (and male) subjects with reproductive potential must agree to use two FDA approved methods of birth control for the entire duration of the study. Potential subjects of childbearing potential should agree to use effective contraception for the entire 2-year period.
10. Adequate venous access to support study required blood draws.

Exclusion Criteria:

1. Inability or unwillingness of a subject to give written informed consent or comply with study protocol.
2. BMI>28 kg/m.
3. HbA1c > 9%
4. Subjects with poorly controlled hypertension as defined by systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg.
5. Subjects with any history of cardiac disease, including but not limited to myocardial infarction, uncompensated heart failure, fluid overload, as well as any clinically significant abnormality identified on prior cardiac stress test, angiogram evaluation, or echocardiogram.
6. Subjects with liver disease, portal hypertension, any coagulopathy (including history of Factor V deficiency) or long-term anti-coagulant therapy (except low-dose aspirin). Other hepatic conditions including hepatic anatomic abnormalities or variants that would place the individual at increased risk in the judgment of the investigator are also considered exclusionary.
7. Symptomatic cholecystolithiasis; acute or chronic pancreatitis; or current symptomatic peptic ulcer disease.
8. Subjects with uncontrolled thyroid disease: thyroid stimulating hormone <0.3 mU/L or >5 mU/L; free T4 <5.0 ug/dL or >11.0 ug/dL.
9. Any of the following laboratory findings: hemoglobin <11.5 g/dL (females) or <13.2 g/dL (males); leukocytes <3,000/μL; neutrophils <1,500/μL; lymphocytes <800/μL; platelets <100,000/μL; elevation in AST and ALT >2 x ULN (upper limit of normal); LDL cholesterol >160; Triglycerides >3 x ULN; total bilirubin >1.5 x ULN.
10. Screening laboratory evidence consistent with significant chronic active infection (i.e.., hepatitis B and C, tuberculosis, and HIV), and IGRA Tuberculosis (Tb) test during screening
11. Ongoing acute infections, e.g., acute respiratory tract, urinary tract, or gastrointestinal tract infections.
12. Subjects with eating disorders.
13. Ongoing or anticipated use of diabetes medications other than insulin.
14. Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within 7 days of screening.
15. Recent recipient of any licensed or investigational live attenuated vaccine(s) within 6 weeks of randomization.
16. Patients who have participated in previous clinical studies, other than observational studies, will be excluded.
17. Concomitant therapy with immunosuppressive drugs, immunomodulators, or cytotoxic agents, or previous therapy less than 3 months from randomization.
18. History or diagnosis of malignancy with the exception of a history of localized basal or squamous cell carcinoma.
19. Any history of gastroparesis or other severe gastrointestinal disease.
20. Presence of an allograft.
21. Diagnosed or self-reported drug or alcohol abuse.
22. An individual who has a medical, psychological or social condition that, in the opinion of the Principal Investigator, would interfere with safe and proper completion of the trial.
23. Pregnancy or ongoing breastfeeding for women; unwillingness or inability of both females and males of childbearing age to use a reliable and effective form of contraception, for the entire 2-year duration of the study.
24. Inability to perform any of the assessments required for endpoint analysis.
25. Known history of serious allergic reactions, including anaphylaxis to CELZ-201 or its preparation components. Specifically, patients with a prior history of heparin induced thrombocytopenia or any other adverse reaction to heparin, will be excluded.
26. The investigator believes that participating in the trial is not in the best interest of the patient, or the investigator considers patient unsuitable for enrollment (such as unpredictable risks or subject compliance issues).
27. Positive for coronavirus disease (COVID)-19 by PCR or evidence of active infection per local institutional standards.
28. Allergy to iodine contrast or anesthesia
29. For female subjects: Pregnant, nursing, or planning to become pregnant during the course of entire duration of the study (approximately little over two years) or unwillingness to comply with contraceptive requirements.
30. For male subjects: Male subjects with a female partner who is planning to become pregnant with the male subject during the entire course of the study or unwillingness to comply with contraceptive requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CELZ-201 Treatment Group; Participants in this group will receive a single dose of CELZ-201, in addition to standard of care of care for Type 1 Diabetes treatment.	Biological: CELZ-201 Administration; Participants in this group will receive a single dose of CELZ-201, in addition to standard of care for Type 1 Diabetes treatment. Perinatal tissue derived cells will be administered at a dose of 1x10^6 cells/kg via an intra-arterial infusion into the dorsal pancreatic artery.
Placebo Comparator: Control Group; Participants in this group will receive standard of care for Type 1 Diabetes only.	Other: Control Group; Enhanced standard of care for Type 1 Diabetes treatment only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events	The primary outcome to be assessed is tolerability and safety of the CELZ-201 therapy. The incidence of adverse events (grade 2 or above as per CTCAE version 5.0) in both groups at 6 months.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events	Incidence of adverse events (grade 2 or above as per CTCAE version 5.0) in both groups at 12 months.	12 months
Number of Participants with Adverse Events	Incidence of adverse events (grade 2 or above as per CTCAE version 5.0) in both groups at 24 months.	24 months
Glycosylated HbA1C	Changes in glycosylated HbA1c (%)	12 months
Insulin Requirement	Changes in exogenous insulin requirement	12 months
Islet Autoantibody Levels	Changes in islet autoantibody levels GAD65 (U/mL), IA2 (U/mL), and ZnT8 (U/mL)	12 months
Alloreactive Antibody Levels	Changes in alloreactive antibody levels (U/mL)	12 months
C-peptide during a 4-hour MMTT	Changes in fasting, peak stimulated and AUC C-peptide (ng/mL) during a 4-hour MMTT	12 months

Collaborators and Investigators

• Sponsor: Creative Medical Technology Holdings Inc
• Investigators: Principal Investigator: Camillo Ricordi, MD, University of Miami, Diabetes Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2023
• Primary Completion (Estimated): January 31, 2025
• Study Completion (Estimated): January 31, 2026

Study Registration Dates

• First Submitted: November 7, 2022
• First Submitted That Met QC Criteria: November 15, 2022
• First Posted (Actual): November 25, 2022

Study Record Updates

• Last Update Posted (Actual): July 14, 2023
• Last Update Submitted That Met QC Criteria: July 12, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Type 1 Diabetes; Recent Onset Type 1 Diabetes; Adult Onset Type 1 Diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: CELZ-201-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No