This is a randomized, placebo-controlled, parallel group, multicenter, double-blind Phase 2a, 2-arm study. The goal of this Phase 2a study is to assess safety and efficacy of brivekimig in comparison to placebo to preserve β-cell function in participants with recently diagnosed Stage 3 type 1 diabetes (T1D) on insulin therapy. The study design comprises 2 parts: in Part A adult participants (18 to 35 years of age at screening) and in Part B adolescent and young adult participants (age range 12 to 21 years) will be randomized into brivekimig and placebo groups. Approximately 84 participants will be included with randomization ratio 3:1 (active:placebo). The study includes a screening period (3 to 5 weeks), a double-blind treatment period of 52 weeks and a safety follow-up of 26 weeks.
The total study duration will be up to 83 weeks including Screening and Safety follow-up period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
84
Pharmaceutical form: Solution Route of administration: Subcutaneous injection
Pharmaceutical form: Solution Route of administration: Subcutaneous injection
Atlanta Diabetes Associates- Site Number : 8400006
Atlanta, Georgia, United States
IACT Health - Columbus - Talbotton Road- Site Number : 8400012
Columbus, Georgia, United States
Profound Research - MHP - TriAtria- Site Number : 8400015
Farmington Hills, Michigan, United States
Tekton Research - McKinney- Site Number : 8400017
McKinney, Texas, United States
Advanced Research Institute - Odgen- Site Number : 8400007
Ogden, Utah, United States
Investigational Site Number : 0320001
Buenos Aires, Argentina
Investigational Site Number : 0320002
Buenos Aires, Argentina
Investigational Site Number : 0320005
Buenos Aires, Argentina
Investigational Site Number : 0320004
Buenos Aires, Argentina
Investigational Site Number : 0320003
Salta, Argentina
...and 14 more locations
Change from baseline to Week 26 in mean 2-hour mixed meal tolerance test (MMTT) stimulated C-peptide concentration
Mixed meal tolerance test MMTT stimulated C-peptide concentration is to be calculated from area under the concentration-time curve (AUC)
Time frame: From Baseline to Week 26
Change from baseline to Week 52 in mean 2-hour MMTT stimulated Cpeptide concentration
MMTT stimulated C-peptide concentration is to be calculated from area under the concentration-time curve (AUC)
Time frame: From Baseline to Week 52
Participant remaining C-peptide positive at Week 26 and Week 52
Incidence (yes/no) outcome Defined as mean 2-hour MMTT stimulated C-peptide concentration ≥0.2 nmol/L
Time frame: Week 26 and Week 52
Time in range (TIR) (70-180 mg/dL) at Week 26 and Week 52
Assessed by Continuous glucose monitoring (CGM). A CGM system is a device that records interstitial glucose levels continuously throughout the day and night via a subcutaneous sensor.
Time frame: Week 26 and Week 52
Change from baseline to Week 26 and Week 52 in insulin dose
Expressed in IU/kg/day
Time frame: From Baseline to Week 26 and Week 52
Change from baseline to Week 26 and Week 52 in glycated hemoglobin A1c (HbA1c) level
Time frame: From Baseline to Week 26 and Week 52
Participant having HbA1c ≤6.5% and ≤0.25 IU/kg/day of exogenous insulin required at Week 26 and Week 52
Incidence (yes/no) outcome
Time frame: Week 26 and Week 52
Incidence of treatment emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs) and TEAEs leading to treatment discontinuation
Time frame: Up to End of Study (approx. 83 Weeks)
Incidence (yes/no) of hypoglycemic events (level 2 or 3 according to American Diabetes Association)
Incidence (yes/no) outcome
Time frame: Up to End of Study (approx. 83 Weeks)
Incidence (yes/no) of hyperglycemic episodes (level 2 according to American Diabetes Association)
Incidence (yes/no) outcome
Time frame: Up to End of Study (approx. 83 Weeks)
Incidence (yes/no) of diabetic ketoacidosis (DKA) events
Incidence (yes/no) outcome
Time frame: Up to End of Study (approx. 83 Weeks)
Incidence (yes/no) of clinically significant changes in vital signs, electrocardiogram (ECG), and/or laboratory evaluation
Incidence (yes/no) outcome
Time frame: Up to End of Study (approx. 83 Weeks)
Brivekimig serum concentrations over time
Time frame: Up to End of Study (approx. 83 Weeks)
Incidence of anti-drug antibodies (ADAs) over time
Time frame: Up to End of Study (approx. 83 Weeks)
Change from baseline to Week 26 and Week 52 in Problem Areas in Diabetes (PAID) total score (all participants)
The Problem Areas in Diabetes (PAID) is a diabetes specific instrument measuring diabetes distress. There is an adult version (18+) and a pediatric version for children 8-17 years of age. The PAID contains 20 items that describe negative emotions related to diabetes (eg, depression, anger, frustration). Item scores are summed to generate a total score. Scores range from 0 to 100, where higher total scores correspond to higher emotional distress due to diabetes
Time frame: From Baseline to Week 26 and Week 52
Change from baseline to Week 26 and Week 52 in PAID immediate and theoretical domain scores (caregivers of all participants 12 to 17 y.o.)
Caregiver version of PAID for parents with children 8-18 years of age consists of 18 items that measure caregiver burden. Two scores are calculated: Immediate Burden and Theoretical Burden. Scores range from 0 to 100, where higher scores correspond to greater caregiver burden.
Time frame: From Baseline to Week 26 and Week 52
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