The Safety and Efficiency of a Single Dose of CARC-101C in Patients With Autoimmune Type 1 Diabetes Mellitus

Official title

An Open, Dose-escalation Clinical Study to Evaluation of the Safety and Efficiency of a Single Dose of CARC-101C in Patients With Autoimmune Type 1 Diabetes Mellitus

Overview

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

• Drug CARC-101C
  Subjects enrolled in the project will received a one-dose injection of CARC-101C

Primary outcome measures

• Incidence and severity of adverse events within 3 weeks after administration (NCI CTCAE V5.0). [Time frame: 21 days]

Secondary outcome measures (12)

• Changes of AUC(Area Under Curve) compared with baseline fasting and MMTT-stimulated C-peptide at 4, 12, 24, 36, 52 and 76 weeks. [Time frame: 4, 12, 24, 36, 52 and 76 weeks]
• 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. [Time frame: 4, 12, 24, 36, 52 and 76 weeks]
• Percentage of subjects with HbA1c < 7% at 12, 24, 36, 52 and 76 weeks. [Time frame: 12, 24, 36, 52 and 76 weeks]
• Diachronic change of HbA1c from baseline at 12, 24, 36, 52 and 76 weeks. [Time frame: 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. [Time frame: 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. [Time frame: 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. [Time frame: 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. [Time frame: 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; [Time frame: 12, 24, 36, 52 and 76 weeks]
• Maximum concentration observed (Cmax) of CARC-101C at Day1，Day2，Day5，Day7，Day21，Week4，Week12; [Time frame: Day1，Day2，Day5，Day7，Day21，Week4，Week12]
• Time at which the maximum concentration (Tmax ) of CARC-101C at Day1，Day2，Day5，Day7，Day21，Week4，Week12; [Time frame: Day1，Day2，Day5，Day7，Day21，Week4，Week12]
• AUC up to the last measurable concentratio（AUC (0-t)）: of CARC-101C at Day1，Day2，Day5，Day7，Day21，Week4，Week12; [Time frame: Day1，Day2，Day5，Day7，Day21，Week4，Week12]

Eligibility criteria

Inclusion criteria

• Patients are eligible to be included in this study only if all of the following criteria apply:

• Males and females aged between ≥18 and ≤40 years old at the time of screening.
• 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:

• Must be tested Insulin a(utoantibody)IAA-positive at the time of diagnosis.
• Must not have undergone any form of insulin therapy before diagnosis.
• Currently undergoing insulin therapy and possesses HbA1c levels between ≥7.0% and ≤12%.
• Possess a body mass index (BMI) between at the time of screening ≥18.0 kg/m2 and ≤ 35.0 kg/m2.
• 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).
• 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).
• 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:

• Males and females aged between ≥18 and ≤40 years old at the time of screening.
• 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:

• Must be tested IAA-positive at the time of diagnosis.
• Must not have undergone any form of insulin therapy before diagnosis.
• Currently undergoing insulin therapy and possesses HbA1c levels between ≥7.0% and ≤12%.
• Possess a body mass index (BMI) between at the time of screening ≥18.0 kg/m2 and ≤ 35.0 kg/m2.
• 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).
• 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).
• Must be capable of providing written, signed, and dated informed consent and willing to comply with research requirements in the study.

Exclusion criteria

Patients are not eligible to be included in this study if any of the following criteria apply:

• Average daily total insulin use was >1.0IU/kg(international unit) per day or <15IU per day 7 days before screening.
• Any of the following abnormalities were detected in the laboratory during screening:

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 of ULN
• Total bilirubin >1.5 of ULN
• Hemoglobin <120g/L or > 165g/L (male), or < 110g/L or > 160g/L (female).
• Serum creatinine >1.5 of ULN(Upper limits of normal).
• HIV-Ab or HBsAg or HCV-Ab(Hepatitis C virus) or treponema pallidum positive at screening
• Have a serious/uncontrolled autoimmune disease in addition to T1D at the time of screening.
• Have diabetic retinopathy stage 3 or above in addition requiring laser or surgical procedures 3 months prior to screening.
• Possess pre-existing diseases affecting erythrocyte production and stability, including glucose-6-phosphate dehydrogenase (G6PD) deficiency, autoimmune hemolytic anemia, paroxysmal sleep hemoglobinuria, hereditary spherocytosis, hemoglobinopathy, pyruvate kinase deficiency etc.
• History of acute or chronic pancreatitis.
• History of hereditary bleeding tendency or coagulation dysfunction, or have a history of thrombosis, hemolysis or bleeding.
• Diagnosed with DKA(Diabetic Ketoacidosis) or hyperosmotic hyperglycemia syndrome 1 month before screening.
• Used immunosuppressants 3 months prior to screening.
• Used systemic glucocorticoid therapy 2 weeks prior to screening or during the study period (except for inhaled and topical glucocorticoid therapies).
• Participated in any drug or medical device clinical research within 3 months before screening.
• Previously received cell therapy.
• Previously reported malignant tumors (whether cured or not).
• Systemic infection, severe trauma or other states of stress confirmed by laboratory tests or clinical manifestations at the time of screening.
• Pregnant or lactating women.
• Have other conditions that the investigator considers inappropriate to participate in this clinical study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Prevention

Study locations

China · 1 center

• Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University — Nanjing

Identifiers

NCT: NCT06546436 · KMX-CARC-101C-IIT01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗