This Phase 3, multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy, safety, and tolerability of SAB-142, a fully human anti-thymocyte globulin (h-ATG), in participants aged 5 to 40 years with Stage 3 type 1 diabetes (T1D). The study will enroll participants with recent-onset T1D (\>100 days to \<1 year from diagnosis) and established-onset T1D (≥1 year to ≤2 years from diagnosis) who retain residual beta-cell function as demonstrated by stimulated C-peptide levels \>0.2 nmol/L. Participants will be randomized in a 2:1 ratio to receive SAB-142 or placebo in addition to standard diabetes care. The primary objective is to determine whether SAB-142 preserves beta-cell function over 12 months as measured by stimulated C-peptide response during a mixed meal tolerance test (MMTT). External data from the SAB-142-201 SAFEGUARD study will be incorporated to include participants with new-onset T1D (\<100 days from diagnosis) in the primary efficacy analysis.
Type 1 diabetes is an autoimmune disease characterized by progressive destruction of pancreatic beta cells. SAB-142 is a purified fully human multi-specific anti-thymocyte globulin designed to modulate autoimmune responses while potentially avoiding some of the immunogenicity and adverse effects associated with rabbit-derived anti-thymocyte globulin preparations. This study will evaluate whether SAB-142 preserves endogenous insulin production and improves clinical outcomes in participants with Stage 3 T1D who have residual beta-cell function. The study consists of three disease-duration cohorts: Cohort 1: New-onset T1D (\<100 days from diagnosis; external data from SAB-142-201 SAFEGUARD) Cohort 2: Recent-onset T1D (\>100 days to \<365 days from diagnosis) Cohort 3: Established-onset T1D (365 to 730 days from diagnosis) Approximately 72 participants will be enrolled into Cohorts 2 and 3 and randomized 2:1 to SAB-142 or placebo. An additional 36 age-matched participants from SAB-142-201 SAFEGUARD will comprise Cohort 1, resulting in a combined efficacy dataset of approximately 108 participants. Participants will receive an induction treatment period at baseline and a maintenance treatment period at Month 6. Follow-up continues through Month 12.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
108
University of California San Francisco Benioff Children's Hospital
San Francisco, California, United States
Barbara Davis Center for Diabetes
Aurora, Colorado, United States
University of Florida
Gainesville, Florida, United States
IUH - Riley Hospital for Children - Riley Outpatient Center - Pediatric Diabetes & Endocrinology
Indianapolis, Indiana, United States
Area under the concentration-time curve (AUC) of C-peptide after a 2 hour mixed meal tolerance test (MMTT)
This is a measure of endogenous insulin production and β cell function (change from baseline in C-peptide ln \[AUC+1\].
Time frame: Dose administration to 12 Months
AUC of C-peptide after a 2-hour MMTT in a priori in vitro identified "responders" and "non-responders"
This is achange from baseline in C--peptide ln \[AUC+1\] at 12 months) in a priori in vitro identified "responders" and "non-responders" to SAB-142 and compared to placebo.
Time frame: Baseline, Months 3, 6, 9 and 12
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0
Incidence of treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), and serious adverse events (SAEs).
Time frame: Dose administration to 12 Months
To evaluate the pharmacokinetics (PK) of SAB-142
Evaluate SAB-142 serum concentrations over the infusion
Time frame: Days 1 and 2 of each treatment period (pre- and post-dose/end of infusion [EOI]), plus Week 1 for TP1 (for participants that attend the optional in-clinic visit), Week 4, and Months 3, and 7.
To evaluate the immunogenicity of SAB-142
Incidence and titres of anti-SAB-142 antibodies in serum including neutralising antibodies (nAbs) if indicated.
Time frame: Baseline, Week 1 (for participants that attend the optional in-clinic visit), Week 4, Months 3, 6, 7, 9, and 12.
Immunophenotyping following SAB-142 administration will be performed on PBMC using flowcytometry
Changes in immune cell populations following SAB-142 administration will be performed on PBMC using flowcytometry. All data will be reported as a percentage of lymphocytes and compared to baseline analysis. Populations to be tested: * CD3+CD4+ Tcells * CD3+CD8+ Tcells * CD19+ Bcells
Time frame: Baseline (Day 1, pre-dose), Week 4, Months 3, 6, 7, 9 and 12.
Haemoglobin A1c (HbA1c) levels
Hba1c is a key clinical parameter for looking at improvement in type 1 diabetes .Expressed in % and mmol/molmanagement
Time frame: Baseline, Months 3, 6, 9 and 12
Time in Range (TIR)
Expressed as a daily average of the percentage of time in a 24-hour day a participant's CGM reading is \>70 but ≤180 mg/dL (\>3.9 to ≤10.0 mmol/L), assessed by CGM
Time frame: Baseline, Months 3, 6, 9 and 12
Improvement in Time in Tight Range (TITR)
Expressed as a daily average of the percentage of time in a 24hour day a participant's glucose is \>70 but ≤140 mg/dL (\>3.9 to ≤7.8 mmol/L), assessed using continuous glucose monitoring (CGM)
Time frame: Baseline, Months 3, 6, 9 and 12
Improvement in Time Below Range on a Continuous Glucose Monitor
Time Below Range on a continuous glucose monitor is a key clinical indicator for improvement in type 1 diabetes management
Time frame: Baseline, Months 3, 6, 9 and 12
Improvement in Time Above Range on a Continuous Glucose Monitor
Time Above Range on a continuous glucose monitor is a key clinical indicator for improvement in type 1 diabetes management
Time frame: Baseline, Months 3, 6, 9 and 12
Number of clinically important hypoglycemic episodes
Defined as the total number of Level 2 and 3 hypoglycaemic events and/or episodes of cognitive impairment requiring external assistance for recovery (participant's diary and CGM-based).
Time frame: Baseline, Months 3, 6, 9 and 12
Exogenous Insulin use
Defined as a daily average in units per kilogram per day (U/kg/day) (total daily insulin based on participant's diary at predefined study periods).
Time frame: Baseline, Months 3, 6, 9 and 12
Proportion of participants with partial clinical remission
Defined as an insulin requirement of \<0.25 units per kg of body weight per day and HbA1c \<6.5% (47 mmol/mol).
Time frame: Baseline, Months 3, 6, 9 and 12
Proportion of participants with partial remission
Defined as insulin-dose adjusted A1c (IDAA1c) + \[4 × insulin dose (units per kilogram per 24 h) ≤9
Time frame: Baseline, Months 3, 6, 9 and 12
Total BETA-2 score
A score comprised of fasting plasma glucose (mmol/L), HbA1c (%), daily insulin (U/kg), and fasting C-peptide (nmol/L)
Time frame: Baseline, Months 3, 6, 9 and 12
Insulin dose-adjusted A1c (IDAA1C)
Time frame: Baseline, Months 3, 6, 9 and 12
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