Safety and Pharmacokinetics of CBX129801 in Patients With Type 1 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to assess safety and tolerability and determine the pharmacokinetics of subcutaneous single and multiple (up to 12) dose administration of CBX129801 (long-acting synthetic C-peptide) in type 1 diabetes patients.

Detailed Description
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This study will be conducted in two parts (Part 1 and Part 2). Part 1 will be conducted in three sequential dose cohorts with dose level escalated for each successive cohort. In Part 2 of the study, a dose regimen determined from the pharmacokinetic data from Part 1 will be administered in up to 40 additional subjects to achieve a target plasma concentration range that represents the most commonly observed physiological C-peptide levels in healthy, non-diabetic individuals.

Official Title
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A Randomized, Blinded, Placebo-Controlled, Multiple Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of CBX129801 (Long-Acting Synthetic C-Peptide) After Subcutaneous Administration in Patients With Type 1 Diabetes Mellitus

Conditions
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Type 1 Diabetes, Diabetes Mellitus, Peripheral Diabetic Neuropathy

Intervention / Treatment
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* Drug: CBX129801
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Give informed consent Aged 18 to 55 years (Part 1), Ages 18 to 65 years (Part 2) Stable type 1 diabetes mellitus (T1DM) for a minimum of 5 years Body mass index of 18-35 kg/m2 Be C-peptide deficient (assessed by fasting concentration level) Normal renal function (assessed by serum creatinine) Be in good general health (besides T1DM) Have abnormal sural nerve conduction velocity observed bilaterally (Part 2 only) Key Exclusion Criteria: Any significant cardiovascular, hematological, renal, hepatic, pulmonary, endocrine (except for diabetes mellitus), central nervous, or gastrointestinal condition or disease Unstable glucose control Have had a islet cell, kidney, and/or pancreas transplant Blood loss or blood donation within 56 days Drug or alcohol abuse (within 2 years) or recreational drug use (within 3 months) History or positive test result for Hepatitis B, C, and/or HIV Treatment with medication for peripheral neuropathy within 30 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CBX129801<br> | Drug: CBX129801<br>* Subcutaneous injection<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the single and multiple dose pharmacokinetics of plasma CBX129801 after subcutaneous (SC) administration of CBX129801 by estimating parameters of Cmax, Tmax, Cmin, AUClast, AUCinf, Tlag, Cav, CL/F, Vz/F, and half life. | Plasma CBX129801 will be used to assess the concentration versus time profiles and PK of CBX129801. | For duration of study / 16 months | 
| To assess the safety and tolerability of CBX129801 when administered SC by adverse events, injection site assessments, clinical laboratory tests, vital signs, physical examinations, and electrocardiograms. |  | For duration of study / 16 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the technique of sensory nerve conduction velocity (SNCV) in the sural nerves in patients with type 1 diabetes mellitus. |  | Predose and 6 and 12 weeks postdose | 
| To assess the immunogenicity of CBX129801 by occurrence of anti-CBX129801 antibody formation. |  | For duration of study / 16 months | 
| To evaluate the technique of motor nerve conduction velocity (MNCV) in the peroneal nerves in patients with type 1 diabetes mellitus. |  | Predose and 6 and 12 weeks postdose | 
| To evaluate the technique of vibration perception threshold (VPT) in patients with type 1 diabetes (Part 2 only) |  | Predose and 12 weeks postdose |