Autoimmune Type 1 Diabetes Mellitus(T1DM)
Conditions
Brief summary
This study investigated the safety, efficiency, pharmacokinetics and pharmacokinetics of CARC-101C in patients with autoimmune type 1 diabetes. A single dose, dose escalation, open study design was used.
Interventions
DRUGCARC-101C
Subjects enrolled in the project will received a one-dose injection of CARC-101C
Sponsors
Carcell Biopharma Ltd.
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Patients are eligible to be included in this study only if all of the following criteria apply: 1. Males and females aged between ≥18 and ≤40 years old at the time of screening. 2. Diagnosed with Autoimmune type 1 diabetes(T1D) within 3 to 6 months before screening, based on the 2021 version of the Chinese Guidelines for Diagnosis and Treatment of Type 1 Diabetes, with positive pancreatic autoantibodies: 1. Must be tested Insulin a(utoantibody)IAA-positive at the time of diagnosis. 2. Must not have undergone any form of insulin therapy before diagnosis. 3. Currently undergoing insulin therapy and possesses HbA1c levels between ≥7.0% and ≤12%. 4. Possess a body mass index (BMI) between at the time of screening ≥18.0 kg/m2 and ≤ 35.0 kg/m2. 5. Fasting C-peptide ≥0.10 nmol/L (0.30 ng/ml) or post-MMTT peak C-peptide ≥0.2 pmol/mL (0.6 ng/mL). 6. Males and females of childbearing potential must agree to use highly effective contraception, from providing informed consent till withdrawal or 3 months post-medication (whichever occurs later). 7. Must be capable of providing written, signed, and dated informed consent and willing to comply with research requirements in the study.
Exclusion criteria
* Inclusion Criteria Patients are eligible to be included in this study only if all of the following criteria apply: 1. Males and females aged between ≥18 and ≤40 years old at the time of screening. 2. Diagnosed with T1D within 3 to 6 months before screening, based on the 2021 version of the Chinese Guidelines for Diagnosis and Treatment of Type 1 Diabetes, with positive pancreatic autoantibodies: 1. Must be tested IAA-positive at the time of diagnosis. 2. Must not have undergone any form of insulin therapy before diagnosis. 3. Currently undergoing insulin therapy and possesses HbA1c levels between ≥7.0% and ≤12%. 4. Possess a body mass index (BMI) between at the time of screening ≥18.0 kg/m2 and ≤ 35.0 kg/m2. 5. Fasting C-peptide ≥0.10 nmol/L (0.30 ng/ml) or post-MMTT peak C-peptide ≥0.2 pmol/mL (0.6 ng/mL). 6. Males and females of childbearing potential must agree to use highly effective contraception, from providing informed consent till withdrawal or 3 months post-medication (whichever occurs later). 7. Must be capable of providing written, signed, and dated informed consent and willing to comply with research requirements in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of adverse events within 3 weeks after administration (NCI CTCAE V5.0). | 21 days |
Secondary
| Measure | Time frame |
|---|---|
| Changes of C-peptide compared with baseline in fasting and 2h after MMTT(Mixed-meal tolerance test)-stimulated at 4, 12, 24, 36, 52 and 76 weeks. | 4, 12, 24, 36, 52 and 76 weeks |
| Percentage of subjects with HbA1c < 7% at 12, 24, 36, 52 and 76 weeks. | 12, 24, 36, 52 and 76 weeks |
| Diachronic change of HbA1c from baseline at 12, 24, 36, 52 and 76 weeks. | 12, 24, 36, 52 and 76 weeks |
| Percentage of subjects whose weekly mean insulin requirement decreased by 50% or more at 4, 12, 24, 36, 52 and 76 weeks. | 4, 12, 24, 36, 52 and 76 weeks |
| Diachronic change in weekly mean insulin requirement from baseline at 4, 12, 24, 36, 52 and 76 weeks. | 4, 12, 24, 36, 52 and 76 weeks |
| Homeostatic model assessment of β-cell function (HOMA-β) from baseline at 4, 12, 24, 36, 52 and 76 weeks. | 4, 12, 24, 36, 52 and 76 weeks |
| Time in Range (TIR, time of glucose readings at 3.9 to 10.0 mmol/L) changes from baseline in indicators associated with continuous glucose monitoring at 12, 24, 36, 52 and 76 weeks. | 12, 24, 36, 52 and 76 weeks |
| Percentage of subjects with TIR >70% from baseline by continuous glucose monitors compared with baseline at 12, 24, 36, 52 and 76 weeks; | 12, 24, 36, 52 and 76 weeks |
| Maximum concentration observed (Cmax) of CARC-101C at Day1，Day2，Day5，Day7，Day21，Week4，Week12; | Day1，Day2，Day5，Day7，Day21，Week4，Week12 |
| Changes of AUC(Area Under Curve) compared with baseline fasting and MMTT-stimulated C-peptide at 4, 12, 24, 36, 52 and 76 weeks. | 4, 12, 24, 36, 52 and 76 weeks |
| AUC up to the last measurable concentratio（AUC (0-t)）: of CARC-101C at Day1，Day2，Day5，Day7，Day21，Week4，Week12; | Day1，Day2，Day5，Day7，Day21，Week4，Week12 |
| AUC curve to infinite time（AUC (0--∞)） of CARC-101C at Day1，Day2，Day5，Day7，Day21，Week4，Week12; | Day1，Day2，Day5，Day7，Day21，Week4，Week12 |
| Terminal phase rate constant(λz) of CARC-101C at Day1，Day2，Day5，Day7，Day21，Week4，Week12; | Day1，Day2，Day5，Day7，Day21，Week4，Week12 |
| Terminal phase half-life (t1/2) of CARC-101C at Day1，Day2，Day5，Day7，Day21，Week4，Week12; | Day1，Day2，Day5，Day7，Day21，Week4，Week12 |
| Changes of the T cell subpopulation compared with baseline at 3, 4, 12, 24, 36, 52 and 76 weeks; | 3, 4, 12, 24, 36, 52 and 76 weeks |
| Changes of the presence of pathogenicity related T cells compared with baseline at 3, 4, 12, 24, 36, 52 and 76 weeks; | 3, 4, 12, 24, 36, 52 and 76 weeks |
| Incidence and severity of adverse events within 76 weeks after administration according to version 5.0 of NCI CTCAE. | 76 weeks |
| Changes of Insulin Autoimmune Antibodies(IAA）compared with baseline at 4, 12, 24, 36, 52 and 76 weeks; | 4, 12, 24, 36, 52 and 76 weeks |
| Changes in cytokine levels. | 76 weeks |
| Time at which the maximum concentration (Tmax ) of CARC-101C at Day1，Day2，Day5，Day7，Day21，Week4，Week12; | Day1，Day2，Day5，Day7，Day21，Week4，Week12 |
Countries
China
Outcome results
None listed