Adults (aged 18 to 65 years, inclusive) with T1D
Body mass index (BMI) of 18 to 30 kg/m2 and body weight ≥45 kg
Clinical history and laboratory evidence of T1D, including:
Onset of T1D at <40 years of age
Insulin dependence for ≥5 years at time of signing ICF
Peak stimulated C-peptide level <50 pmol/L (<0.15 ng/mL) or equivalent during MMTT
Historical or current presence of at least one T1D autoantibody including glutamic acid decarboxylase 65 (GAD65), islet antigen 2 (IA2), or zinc transporter 8 (ZnT8) with appropriate documentation In the absence of at least 1 of these T1D autoantibodies, the diagnosis of T1D must be confirmed by the study site’s endocrinologist. If features of another form of diabetes are present, such as monogenic or syndromic forms of diabetes, the historical or current presence of T1D autoantibodies, or negative history of genetic testing of these other forms of diabetes, will be used to confirm T1D diagnosis. Note: Assessment for current presence of T1D (ie, antibodies against GAD65, IA2, and ZnT8) will not include insulin autoantibodies (IAA). Historical T1D autoantibodies may include IAA if the sample was collected prior to starting exogenous insulin or ≤10 days after starting exogenous insulin.
Insulin and HbA1c parameters as defined by all the following:
Insulin requirements: ≤0.8 U/kg/day
Total daily insulin requirement between 10 and 55 U/day (inclusive)
HbA1c: ≤9.5% (80 mmol/mol)
History of intensive diabetes management under the direction of an endocrinologist, diabetologist, or diabetes specialist with ≥2 documented clinical evaluations (based upon subject’s level of glycemic control and overall management) within the 12 months prior to signing the informed consent form (ICF)
Consistent use of the same personal CGM in conjunction with continuous use of the same insulin pump via a hybrid closed loop (HCL) system for at least 3 months prior to signing the ICF and during the study, as well as willingness to use an additional study-provided CGM periodically during the study.
Provide voluntary written consent before performance of any study-related procedures not part of standard medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
Willingness and ability to comply with scheduled visits and study procedures
Prior deceased donor or SC-derived islet cell transplant, organ transplant, or cell therapy
Occurrence of a severe hypoglycemic event (SHE) or diabetic ketoacidosis (DKA; not attributed to insulin pump failure) within 6 months prior to signing the ICF or ≥2 SHEs or ≥2 DKA (not attributed to insulin pump failure) events as determined by the Investigator within 1 year prior to signing the ICF
Prior or current positivity for major histocompatibility complex (MHC) class I chain-related protein (MIC) A/B antibodies
Evidence of scarring or fibrosis at the intended transplantation site, as determined by clinical examination or prior imaging, or medical history of non-traumatic intramuscular (IM) bleeding, including but not limited to spontaneous hematoma formation or bleeding diatheses; history of impaired wound healing or excessive local reaction (eg inflammation, infection, and/or necrosis) to a prior surgical procedure
Blood transfusion within 3 months before signing the ICF or known hemoglobinopathy, chronic anemia, or any condition known to interfere with the measurement of HbA1c
Inadequate organ function as confirmed by clinical laboratory values specified below:
Hepatic function: Aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin >1.5 × the upper limit of normal (ULN). If known Gilbert syndrome, total bilirubin >3.0 mg/dL (51.3 μmol/L)
Renal function:
Estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 calculated using the subject’s measured serum creatinine and a validated equation
Sustained macroalbuminuria as represented by 2 consecutive spot urine tests (>300 mg/g creatinine; first morning sample preferred) and confirmed by a 24-hour urine collection (urine albumin creatinine ratio [UACR] >300 mg albumin/g creatinine/24 hours). Note: Subjects with macroalbuminuria may be managed with medication to eliminate macroalbuminuria which can be adjusted during the Screening Period but must be stable within 2 weeks prior to re-evaluation of this exclusion criterion.
Hematologic:
Hemoglobin <10 g/dL
Neutropenia (<1,000/µL), except for benign neutropenia following consultation with hematologist
Thrombocytopenia (platelet count <100,000/µL)
Cardiac: Inadequate blood pressure control as defined by systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg Note: Blood pressure may be managed with medication that can be adjusted during the Screening Period but must be stable within 2 weeks prior to SC451 transplantation.
Any clinically significant history of, or signs and/or symptoms within 6 months prior to signing the ICF consistent with cardiovascular, cerebrovascular, or peripheral vascular disease.
Advanced complications associated with diabetes including untreated proliferative retinopathy, skin ulcers, or amputation attributable to diabetes
Clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to T1D (ie, cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, or infectious diseases)
Presence of abnormal thyroid function or inadequate thyroid hormone replacement therapy as determined by the Investigator
History of malignancy other than non-melanoma skin cancer or carcinomain-situ (eg, cervix, bladder, breast) or early-stage prostate cancer (eg, Gleason score ≤6, stage 1 or 2), unless disease-free for at least 5 years
Clinically significant active or chronic infection, such as Hepatitis B, Hepatitis C, and/or HIV
Inability to undergo MRI imaging (eg, due to implanted metallic devices, claustrophobia)
History of hypersensitivity to any of the components of SC451 drug product or products required in the surgical administration of SC451
Treatment with any investigational products within 28 days or 5 half-lives (whichever is shorter) before treatment with SC451. If a subject has received any prior treatment with an investigational therapy, the specific product, duration of use, and last use will be documented. Prior, current, or anticipated future use of anti-CD47 therapies is excluded. Current or anticipated future use of flucytosine is also excluded.
Use of systemic immunosuppressive agents, systemic steroids, or non-insulin antihyperglycemic agents 30 days prior to signing the ICF or anticipated during the study Exception: Topical or inhaled steroids and oral prednisone ≤5 mg daily (or equivalent hydrocortisone or prednisolone dose used for physiological replacement) are permitted
Treatment with major surgery within 28 days before signing the ICF (minor surgical procedures are permitted) or anticipated thereafter during the first 24 months after receiving SC451 Note: Patients with prior surgery involving a muscle used for SC451 transplantation will be excluded.
Known active alcohol or substance abuse, or cannabinoids or tobacco use, during the 6 months prior to signing the ICF
Reproductive criteria:
Pregnancy: Woman of childbearing potential (WOCBP) who is pregnant or tests positive for pregnancy during the Screening Period or within 7 days prior to SC451 transplantation. A WOCBP is defined as a female who is not postmenopausal or who has not had a hysterectomy, has functional ovaries, and no documented impairment of oviductal or uterine function that would cause sterility. This category includes females with oligomenorrhoea (even severe), females who are perimenopausal, or have just begun to menstruate. Postmenopausal is defined as females over the age of 55 who have not had a menstrual period for ≥1 year and/or status confirmed by a follicle stimulating hormone (FSH) test.
Contraception: WOCBP who does not agree to use 1 highly effective method of contraception and 1 additional effective (barrier) method at the same time, from the time of signing the ICF and through at least 24 months following SC451 transplantation.