NCT06575426招募中1 期
A Phase I/IIa, Single Site, Open-Label, Ascending Dose Study to Evaluate the Safety and Efficacy of OPF-310 [Encapsulated Porcine Islet Cells for Xenotransplantation] in Subjects With Type 1 Diabetes Mellitus
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Percentage of Subjects Reaching the Efficacy Goal
研究概览
简要总结
This study is First In Human study for Encapsulated Porcine Islet Cells for Xenotransplantation (OPF-310). The purpose of this study to assess the safety, tolerability, and efficacy of OPF-310 transplantation and to define the recommended Phase 2 dose (RP2D) in adult subjects with unstable Type 1 Diabetes Mellitus (T1DM) and a level 3 (severe) hypoglycemic episode at least three times within the 1 year prior to enrollment despite treatment with a closed loop system (CLS) for at least 6 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject must be aged 35 to 70 years of age inclusive, at the time of signing the informed consent.
- •Subject has an established diagnosis of type 1 diabetes mellitus (T1DM) (in accordance with the American Diabetes Association's criteria), with a minimum duration since diagnosis of 5 years.
- •If one of the following criteria (either a or b) applies:
- •Subject has unstable T1DM, not achieving adequate control after receiving CLS (CGM:Dexcom G6, insulin pump: Omnipod® 5 or t:slim X2) under care of a qualified diabetes team for at least 6 months prior to enrollment.
- •Subject has unstable T1DM, not achieving adequate control after receiving CLS (CGM:Dexcom G7, insulin pump: Omnipod® 5, t:slim X2, iLet Bionic Pancreas or The Tandem Mobi System) under care of a qualified diabetes team for at least 6 months prior to enrollment.
- •If one of the following criteria (either a, b or c) applies:
- •Subject has had a Level 3 (severe) hypoglycemic episode (defined as having cognitive impairment requiring external assistance for recovery) at least three times within the 1 year prior to enrollment recorded in the medical record or patient log.
- •Subject has had a Level 3 (severe) hypoglycemic episode at least once within the 1 year prior to enrollment and demonstrates a Clarke Score ≥4, assessed by trained study personnel. The SHE(s) and Clarke Score must be recorded in the medical record or patient log.
- •Subject has had TBR >1% at glucose levels below 70mg/dL and demonstrates a Clarke Score≥4, assessed by trained study personnel. TBR data used for screening and Clarke score must be recorded in the medical record or patient log.
- •Subject has C-peptide <0.3 ng/mL following a mixed meal tolerance test or undetectable fasting C-peptide.
- •Hemoglobin A1C (HbA1c) ≤ 9.0
- •Contraceptive use must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
- •Subject who can agree to cooperate with lifetime follow-up after transplantation.
- •Subject is capable of providing signed informed consent
排除标准
- •Previous history of insulin resistance (defined as an average insulin dose requirement ≥ 0.8 unit/kg/day for 1 week prior to enrollment).
- •Subject has latent autoimmune diabetes in adults (LADA), ketosis-prone (Flatbush) diabetes, or maturity onset diabetes of the young (MODY).
- •CRP ≥ 10 mg/L.
- •Clinically unstable thyroid disease (thyroid stimulating hormone (TSH)< the lower limit of the normal range of TSH at the site.) Patients with subclinical hyperthyroidism can be rescreened once TSH levels normalize due to treatment or other factors.
- •History of malignancies within the past 5 years, excluding basal and squamous cell carcinoma
- •Positive serologies or nucleic acid testing for human immunodeficiency virus (HIV), hepatitis C, and hepatitis B.
- •Active or untreated proliferative diabetic retinopathy. Subjects may be rescreened once they are successfully treated.
- •Serious comorbid conditions that are likely to affect participation in the study, including:
- •Within the last 12 months, peripheral vascular disease with previous amputation.
- •History of New York Heart Association (NYHA) class II, III or IV congestive heart failure (CHF) and/or chronic atrial fibrillation.
- •Chronic obstructive pulmonary disease (COPD) or asthma with previous hospitalization for decompensation; a requirement for mechanical ventilation at any stage; or long- term treatment with oral corticosteroids.
- •Macroalbuminuria (> 300 mg albumin/gm creatinine).
- •Estimated glomerular filtration rate (eGFR) cut-off of < 30 ml/min for all per Kidney Disease Improving Global Outcomes (KDOQI) and Kidney Disease Outcomes Quality Initiative (KDIGO) consensus.
- •Use of warfarin or other anticoagulant therapy (except aspirin), or prothrombin time and international normalized ratio (PT-INR) > 1.5
- •Adrenal insufficiency being treated with corticosteroids
- •Previous pan-peritonitis
- •Previous cardiovascular or cerebrovascular disease. NOTE: For the purposes of this exclusion criterion, "previous cardiovascular disease" is defined as the presence of co-existing cardiac disease, characterized by any of the following conditions:
- •Recent myocardial infarction (within past one year), or
- •Angiographic evidence of non-correctable coronary artery disease, or
- •Evidence of ischemia on functional cardiac exam (with a stress echo test recommended for subjects with a history of ischemic disease), or
- •Heart failure > NYHAII For subjects aged 65 to <70 years who do not meet Exclusion Criterion 12 but have a history of cardiovascular or cerebrovascular disease related to the conditions above, a cardiology consultation (and consultation with other relevant specialists, as appropriate) will be required during the screening period to confirm suitability for general anesthesia and laparoscopic surgery.
- •Patients with hematopoietic stem cell abnormalities (e.g., aplastic anemia, myelodysplastic syndrome)
- •Patients who received a blood transfusion in the previous 90 days, are anticipated to undergo surgery during the 1-year study period that may require transfusion, or have donated blood within the previous 90 days.
- •Previous receipt of an organ, skin allograft, or other tissue transplant from an allogeneic human or animal donor.
- •Treatment with immunosuppressive medication.
- •Previous abdominal surgery, excluding uncomplicated appendectomy, cholecystectomy, exploratory laparoscopy and hernia repair performed prior to 12 weeks prior to enrollment.
- •Treatment with any hypoglycemic medication prescribed for glycemic control, other than insulin therapy.
- •Treatment with acetaminophen or hydroxycarbamide.
- •Use of any investigational products within 12 weeks of enrollment (before entering run-in) or 5 half-lives of the investigational product, whichever is greater.
- •Subject has history of allergy to antibiotics (Amphotericin B, Cefazolin, Ciprofloxacin, Gentamicin), which are used during manufacture of OPF-
- •Previous history of insulin allergy (including porcine insulin), pork product allergy or alginate/seaweed allergy.
- •Panel reactive antibodies (PRA) > 80 %.
- •Active drug, substance or alcohol addiction.
- •Body mass index (BMI) >27 kg/m
- •Any other condition that, in the opinion of the Investigator, may interfere with adherence to the study protocol, including dementia, psychiatric disorder, medical condition, or a history of non-adherence to appointments or treatments
研究组 & 干预措施
OPF-310
Experimental
13 patients will be transplanted OPF-310.
干预措施: OPF-310 (Combination Product)
结局指标
主要结局
Percentage of Subjects Reaching the Efficacy Goal
时间窗: One year after transplant
A successful primary endpoint was defined as achieve both an HbA1c \< 7 % and a reduction of at least 0.5% from baseline, and absence of a Level 3 (severe) hypoglycemic episode from 12 weeks to 52 weeks post-transplant.
Percentage of Subjects Reaching the Efficacy Goal
时间窗: One year after transplant
A successful primary endpoint was defined as achieve both an HbA1c \< 7 % and a reduction of at least 0.5% from baseline, and absence of a Level 3 (severe) hypoglycemic episode from 12 weeks to 52 weeks post-transplant.
次要结局
- Percentage reduction in nocturnal hypoglycemic event rate(12 week, 24 week 52 weeks after transplant)
- Percentage improvement in time below range (<70 mg/dl) by continuous glucose monitoring (CGM)(12 week, 24 week 52 weeks after transplant)
- Percentage improvement in time in range (70-180 mg/dl) by CGM(12 week, 24 week 52 weeks after transplant)
- Percentage improvement in time above range (>180 mg/dl) by CGM(12 week, 24 week 52 weeks after transplant)
- Change in mean amplitude of glycemic excursion (MAGE) by CGM.(12 week, 24 week 52 weeks after transplant)
- Percentage reduction in daily average of insulin use(12 week, 24 week 52 weeks after transplant)
- Percentage of subjects with an HbA1c < 7.0 % assessed at 52 weeks post-transplant(One year after transplant)
- Percentage of subjects with an HbA1c ≤ 6.5 % assessed at 52 weeks post-transplant(One year after transplant)
- Percentage of subjects with positive porcine C-peptide qualitatively assessed by digital ELISA assay(One year after transplant)
- Percentage of subjects with improved awareness of hypoglycemia, as defined by a change in Clarke questionnaire score from ≥ 4 to < 4.(For one year after transplant)
- Values of porcine C-peptide, human c-peptide, and glucose during mixed meal tolerance test (MMTT) and Intravenous Glucose Tolerance Test (IVGTT) at each measuring point(For one year after transplant)
- Psychological impact as assessed by the Diabetes Distress Scale (DDS) and the Hypoglycemic Fear Survey (HFS) at each measuring point.(For one year after transplant)
- Percentage reduction in nocturnal hypoglycemic event rate(12 week, 24 week 52 weeks after transplant)
- Percentage improvement in time below range (<70 mg/dl) by continuous glucose monitoring (CGM)(12 week, 24 week 52 weeks after transplant)
- Percentage of subjects with an HbA1c < 7.0 % assessed at 52 weeks post-transplant(One year after transplant)
- Values of porcine C-peptide during mixed meal tolerance test (MMTT) and Intravenous Glucose Tolerance Test (IVGTT) at each measuring point(For one year after transplant)
- Percentage improvement in time in range (70-180 mg/dl) by CGM(12 week, 24 week 52 weeks after transplant)
- Percentage improvement in time above range (>180 mg/dl) by CGM(12 week, 24 week 52 weeks after transplant)
- Percentage of subjects with an HbA1c ≤ 6.5 % assessed at 52 weeks post-transplant(One year after transplant)
- Change in mean amplitude of glycemic excursion (MAGE) by CGM.(12 week, 24 week 52 weeks after transplant)
- Percentage reduction in daily average of insulin use(12 week, 24 week 52 weeks after transplant)
- Percentage of subjects with positive porcine C-peptide qualitatively assessed by digital ELISA assay(One year after transplant)
- Psychological impact as assessed by the Diabetes Distress Scale (DDS) at each measuring point.(For one year after transplant)
- Percentage of subjects with improved awareness of hypoglycemia, as defined by a change in Clarke questionnaire score from ≥ 4 to < 4.(For one year after transplant)
研究者
研究点 (1)
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