VV-14300: VV-14300 will be administered via ultrasound-guided intramuscular injections.
VV-14299: VV-14299 will be co-administered with VV-14300 via ultrasound-guided intramuscular injections.
Study summary
This study is testing VV-14299 and VV-14300 or VV-14300 alone in adults with long-standing type 1 diabetes (T1D) whose blood sugar is not well controlled despite using an automated insulin delivery (AID) system. VV-14299 and VV-14300 are investigational gene therapies that are injected into muscle and are designed to work together to help remove excess sugar from the blood.
Eligibility
Sex
ALL
Min age
18 Years
Max age
65 Years
Healthy volunteers
No
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.
Primary outcome measure(s)
Incidence and severity of adverse events, abnormal clinical laboratory values, abnormal physical exams, and abnormal vital signs — 52 Weeks Safety of VV-14299 and/or VV-14300
Change from Baseline in blood glucose as measured by continuous glucose monitoring (CGM) — 16 Weeks Efficacy of VV-14299 and/or VV-14300 (Part 1)
Change from Baseline in blood glucose as measured by hemoglobin A1c (HBA1c) level — 16 Weeks Efficacy of VV-14299 and/or VV-14300 (Part 1)
Change from Baseline in blood glucose as measured by fructosamine level — 16 Weeks Efficacy of VV-14299 and/or VV-14300 (Part 1)
Change from Baseline in blood glucose as measured by mixed meal tolerance test (MMTT) — 16 Weeks Efficacy of VV-14299 and/or VV-14300 (Part 1)
Mean change from Baseline in HbA1c levels — 26 Weeks Efficacy of VV-14299 and/or VV-14300 (Part 2)
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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