A Phase 2b, Randomised, Double-Blind, Placebo-Controlled, Parallel-Arm Dose Finding Study Evaluating the Efficacy and Safety of SAB-142 for Delaying the Progression of Type 1 Diabetes (T1D) in Patients with Stage 3 New Onset of Type 1 Diabetes (NOT1D)

The primary objectives of this study are to evaluate the safety and tolerability of two dosing regimens of SAB-142, a human polyclonal immunoglobulin G against thymocytes, in patients recently diagnosed with Stage 3 type 1 diabetes, and to determine whether the investigational treatment can delay the decline of pancreatic beta-cell function during the study period. These objectives are clinically relevant as preserving residual insulin-producing capacity in newly diagnosed type 1 diabetes patients may improve glycemic control, reduce the risk of acute and chronic complications, and potentially alter disease progression.

No secondary objectives have been specified for this trial.

This clinical trial enrolled a total of **124 participants** recently diagnosed with **Stage 3 type 1 diabetes**. The study population included both **male and female** participants, encompassing **adolescents** and **adults** up to **40 years of age**. Participants were selected based on a recent diagnosis of Stage 3 type 1 diabetes and were required to test positive for at least one **antibody** associated with type 1 diabetes. The trial included a **vulnerable population**. Key inclusion criteria required participants to be current with vaccinations as mandated by local or national health authorities. Female participants were required to meet specific conditions to prevent pregnancy during the study, including pre-menarchal status, post-menopausal status, surgical sterilization, or use of reliable contraception. Participants were prohibited from engaging in other experimental treatments during the trial period.

This is a Phase 2b, randomized, double-blind, placebo-controlled, parallel-arm dose finding study designed to evaluate the efficacy and safety of SAB-142 in delaying the progression of Type 1 Diabetes in patients with Stage 3 new onset of the disease. The investigational medicinal product SAB-142 is a solution for infusion containing human polyclonal immunoglobulin G against thymocyte, administered via intravenous administration. The control group receives sodium chloride solution for infusion as placebo, administered via intravenous use. The maximum treatment period for both the test product and placebo is 6 months. The study is expected to commence recruitment in March 2026 and is estimated to conclude in March 2029, representing an overall trial duration of approximately three years.

The primary objectives of this trial are twofold: to assess the safety and tolerability of two study treatment regimens in individuals recently diagnosed with Stage 3 Type 1 Diabetes, and to determine whether the investigational treatment can decelerate the decline of insulin-producing cells in the pancreas throughout the study period. The primary endpoints include the recording and review of any adverse events or side effects occurring during the study, as well as the evaluation of pancreatic function measures related to insulin production. Secondary endpoints focus on monitoring blood glucose control, including data obtained from continuous glucose monitoring devices.

Eligible participants must be up to 40 years of age and recently diagnosed with Stage 3 Type 1 Diabetes. Additional inclusion criteria require participants to be current with vaccinations mandated by local or national health authorities, to have a positive test result for at least one diabetes-associated antibody, and to agree not to participate in other experimental treatments during the study period. Female participants must meet specific conditions to prevent pregnancy during the trial, such as being premenarchal, postmenopausal, having undergone certain surgical procedures, or utilizing reliable contraceptive methods. The expected duration of participant involvement extends throughout the treatment period and subsequent follow-up visits until study completion.

The study design incorporates a systematic sequence of visits to ensure comprehensive monitoring and data collection. Participants undergo a screening visit to confirm eligibility based on the established inclusion criteria. Following enrollment, participants attend scheduled follow-up visits throughout the treatment phase and observation period to assess treatment response, monitor safety parameters, and collect efficacy data. The end-of-study visit marks the conclusion of participant involvement and includes final assessments of all primary and secondary outcome measures. Early termination from the study may occur under specific circumstances as defined in the protocol, which may include withdrawal of consent, development of exclusion criteria, safety concerns, or other protocol-specified conditions requiring discontinuation.

The experimental treatment in this study is **SAB-142**, which contains **human polyclonal immunoglobulin G against thymocyte** as the active substance. This substance is classified as a structurally diverse substance derived from blood. SAB-142 is supplied as a **solution for infusion** and is administered via **intravenous administration**. The dosage is expressed in **milligrams per kilogram** (mg/kg) body weight. The maximum treatment period is **6 months**.

The comparator treatment used in this study is **sodium chloride**, which serves as a **placebo**. Sodium chloride is a chemical substance formulated as a **solution for infusion** and administered via **intravenous use**. The maximum daily dose is **500 millilitres** (ml), with a maximum total dose of **1000 millilitres** (ml). The maximum treatment period for the placebo is **6 days**.

Efficacy will be assessed through the evaluation of pancreas function measures related to **insulin production**. Additionally, **blood sugar control** will be monitored as a secondary parameter, with data collected from **continuous glucose monitoring devices**. These assessments are designed to determine whether the study treatment can help slow the decline of insulin-producing cells in the pancreas over the course of the study.