Phase 2 study for people with Type 1 Diabetes

Reproduced exactly, unedited. Written for researchers rather than for patients.

Inclusion Criteria:

• Able to provide signed informed consent.
• 18 to 65 years of age (inclusive) at Screening.
• Body mass index (BMI) of 20.0 to <30.0 kg/m².
• Clinical diagnosis of Type 1 Diabetes (T1D) for at least 5 years prior to Screening, currently managed with an Automated Insulin Delivery (AID) system for at least 3 months prior to Screening.
• Suboptimal glycemic control (C-peptide <0.20 ng/mL [0.667 nmol/L] during a mixed meal tolerance test; HbA1c >7% and <10%); and on a stable insulin regimen at Screening.
• Adequate kidney function (estimated glomerular filtration rate [eGFR] >60 mL/min/1.73m²) at Screening.
• Females of child-bearing potential must have a negative pregnancy test at Screening and prior to dosing; participants must agree to use highly effective contraception during and for at least 12 months after study intervention administration
• Agree to refrain from donating blood, plasma, platelets, eggs, or sperm during the 12-month Post-Treatment Follow-up Period.
• Willing and able to complete all study visits, procedures, and required use study-provided monitoring devices for the duration of the study.

Exclusion Criteria:

• Type 2 diabetes or other condition requiring exogenous insulin that is not due to autoimmunity, or when insulin delivery is not managed through an AID system.
• Diabetic complications (e.g., severe/proliferative retinopathy or neuropathy) or a clinically significant medical, cognitive, or psychiatric condition that, in the Investigator's opinion, poses additional risk or would make consistent study follow-up unlikely.
• Pregnant or breastfeeding.
• History of malignancy requiring chemotherapy and/or radiation within the 12 months prior to Screening, except for successfully treated non-melanoma skin cancers (e.g., basal cell, squamous cell carcinomas), cervical intraepithelial neoplasia, and localized prostate cancer.
• Clinically significant cardiovascular or cerebrovascular disease, uncontrolled blood pressure, family history of Long QT syndrome, or clinically significant ECG abnormality.
• Significant history of alcohol or drug abuse, or positive alcohol breath test or urine drug screen at the Screening or Run-in visit.
• Plans to implement new strenuous physical activity (e.g., significantly increased running pace/duration, high-intensity interval training, heavy weightlifting, vigorous cycling) during the study.
• Impaired awareness of hypoglycemia.
• Documented anti-AAV1 neutralizing antibody titer above the protocol-specified threshold at Screening.
• Active hepatitis B or C infection, positive HIV serology, or any latent or active infection that would interfere with study procedures or be exacerbated by study medications.
• Clinically significant abnormal Screening laboratory or other diagnostic findings (including hepatic, hematologic, thyroid, muscle-enzyme, or tuberculosis screening) rendering the participant unsuitable for the study.
• Current or recent use of medications that could interfere with glucose metabolism or confound study assessments (e.g., glucocorticoids, systemic beta-blockers, growth hormone, or other antidiabetic medications [e.g., glucagon-like peptide 1 (GLP-1) receptor agonists and/or sodium-glucose cotransport 2 (SGLT2) inhibitors]).
• Vaccination within 30 days prior to dosing or planned vaccination within 8 weeks post-dosing.
• Screening laboratory findings indicating undue risk of a tocilizumab-related adverse event.
• History of bariatric surgery within the 12 months prior to Screening.
• History of trauma to, or other findings affecting the suitability of, the muscles intended for study intervention administration.
• Participation in another investigational drug or biologic trial within 6 months prior to Screening, or participation in any previous gene therapy trial.