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A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Efficacy of VX-880 in Subjects Who Have Type 1 Diabetes Mellitus With Impaired Hypoglycemic Awareness and Severe Hypoglycemia

Phase 1
Conditions
Type 1 Diabetes Mellitus with Impaired Hypoglycemic Awareness and Severe Hypoglycemia
MedDRA version: 20.0Level: PTClassification code 10012601Term: Diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders
MedDRA version: 21.1Level: LLTClassification code 10081605Term: Severe hypoglycemiaSystem Organ Class: 10027433 - Metabolism and nutrition disorders
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
Registration Number
EUCTR2022-002292-11-IT
Lead Sponsor
VERTEX PHARMACEUTICALS INCORPORATED
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
17
Inclusion Criteria

1. Clinical history and laboratory evidence of T1D
2. At least 2 episodes of severe hypoglycemia (confirmed by independent adjudication for subjects in Parts B and C) in the 12 months prior to signing of informed consent at Screening.
3. Reduced awareness of hypoglycemia at Screening
4. Consistent use of continuous glucose monitor (CGM) for at least 3 months before Screening
5. Compatible blood group (A or AB)
Please refer to Section 8.1 of the Protocol for additional inclusion criteria
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 16
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion Criteria

1. Prior islet cell transplant, organ transplant, or cell therapy
2. Advanced complications associated with diabetes including untreated proliferative retinopathy, skin ulcers, or amputations attributable to diabetes.
3. Subjects who have any 1 of the following criteria:
o Insulin requirements: >0.8 U/(kg*day), >55 U/day, or <10 U/day;
o HbA1c: <6.0% or >9.5%
4. Clinically significant active infection or chronic infection such as hepatitis B, hepatitis C, human immunodeficiency virus (HIV), and/or tuberculosis (TB); or invasive aspergillus, histoplasmosis, or coccidioidomycosis infection within 1 year prior to signing of informed consent at Screening.
5. Negative screen for Epstein-Barr virus (EBV) by immunoglobulin G (IgG) determination

Please refer to Section 8.2 of the Protocol for additional exclusion criteria

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: Evaluate the efficacy of VX-880 infusion in subjects who have T1D with impaired hypoglycemic awareness and severe hypoglycemia;Secondary Objective: - Evaluate the efficacy of VX-880 infusion on insulin independence<br>- Evaluate VX-880 islet cell function over time<br>- Evaluate the safety and tolerability of VX-880 infusion in subjects who have T1D with impaired hypoglycemic awareness and severe hypoglycemia;Primary end point(s): Part A<br>• Safety and tolerability assessments<br>Part B<br>• Safety and tolerability assessments<br>• Number of subjects with peak C-peptide =100 pmol/L during mixed meal tolerance test (MMTT)<br>Part C<br>• Proportion of subjects free of severe hypoglycemic events (SHEs) from Day 90 through Day 365 (inclusive) and with either a glycosylated hemoglobin (HbA1c) <7.0% or a =1% reduction in HbA1c from baseline (at one time point) between Day 180 and Day 365 after VX-880 infusion;Timepoint(s) of evaluation of this end point: Please refer to the protocol
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): • Proportion of subjects who are insulin independent (at one timepoint) between Day 180 and Day 365 after VX-880 infusion<br>• Proportion of subjects with peak C-peptide =100 pmol/L during MMTT over time.<br>• Safety and tolerability assessments;Timepoint(s) of evaluation of this end point: Please refer to the protocol
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