EndoBarrier System Pivotal Trial(Rev E v2)

Study Overview
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Brief Summary
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A Randomized, Multi-Center, Pivotal Efficacy and Safety Study Evaluating the EndoBarrier System for Glycemic Improvement in Patients with Inadequately Controlled Type 2 Diabetes and Obesity, the STEP-1 Study. A multi-center, double-blinded, randomized, sham-controlled trial to evaluate the safety and effectiveness of the EndoBarrier System plus moderate intensity lifestyle and dietary counseling compliant with 2019 ADA Standard of Care as compared to a sham control receiving moderate intensity lifestyle and dietary counseling. Both the treatment and sham group will practice medical management compliant with STEP-1 Study Guidelines. Patients will be randomized 3 (EndoBarrier):1 (Sham).

Detailed Description
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The objective of this study is to evaluate the safety and effectiveness of the EndoBarrier System when used with moderate intensity lifestyle and dietary counseling and medical management, in patients with baseline HbA1c ≥ 8.0% and ≤10%, and BMI ≥ 30 kg/m2 and ≤ 50kg/m2, whose diabetes medications consist of at least dual therapy for 3 months, excluding insulin, yet have not achieved adequate HbA1c control (<7%). Specific objectives of this study are: To determine if the EndoBarrier System significantly improves glycemic control To determine that the EndoBarrier System can be safely used to improve glycemic control

Official Title
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A Randomized, Multi-Center, Pivotal Efficacy and Safety Study Evaluating the EndoBarrier® System for Glycemic Improvement in Patients With Inadequately Controlled Type 2 Diabetes and Obesity

Conditions
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Diabetes type2, Obesity

Intervention / Treatment
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* Device: EndoBarrier Liner
* Other: Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥30 years and ≤ 65 years Have understood and signed the approved informed consent form Diagnosis of type 2 diabetes for ≤ 15 years HbA1c ≥ 8.0% and ≤10% BMI ≥30kg/m2 and ≤ 50kg/m2 Willing and able to comply with study requirements Documented negative pregnancy test in women of childbearing potential Women of childbearing potential not intending to become pregnant (continue to be on an approved form of birth control) for the duration of their trial participation, including post explant period. Women of child-bearing age without known sterilization will be placed on 2 forms of birth-control to prevent unwanted pregnancies At least one year of medical records available, including detailed medical therapy and dosing information Failed to achieve adequate HbA1c reduction (<8%) after dual therapy for at least 3-month stable dosage of diabetes medication(s), including metformin, SGLT-2 inhibitor, GLP-1 RA or, other medications including meglitinides, sulfonylureas, thiazolidinediones, or DPP-4s. Use of insulin is an exclusion criterion. Patients should be at 70% of maximum dosage of diabetes medications or highest tolerable dosage. Exclusion Criteria: Previous treatment with the EndoBarrier System Previous GI surgery that could preclude the ability to place the EndoBarrier Liner or affect the function of the EndoBarrier Liner, or abnormal GI anatomical finding that could preclude the ability to place the EndoBarrier Liner or affect the function of the EndoBarrier Liner Known history of liver disease (e.g., viral or autoimmune etiology, METAVIR grade 2 or higher fibrosis/cirrhosis from a biopsy within the past 6 months, but not including incidental fatty liver) eGFR of less than 45 ml/min/1.73 m2 Prior history of an abscess requiring hospitalization, intravenous antibiotics or drainage Previous treatment for severe liver disease and/or biliary tract disease, including but not limited to, surgery, bile duct dilatation, and stent placement Diagnosis of type 1 diabetes mellitus or having any history of ketoacidosis Fasting C-peptide < 1.0 ng/mL Triglyceride level > 600 mg/dL Vitamin D deficiency (<20ng/ml) Uncorrectable bleeding diathesis, platelet dysfunction, thrombocytopenia with platelet count less than 100,000/microliter, or known coagulopathy Height < 5 feet (152.4 cm) Current or past alcohol addiction, current or past drug addiction, or current drug usage, of drugs such as, narcotics, opiates, or benzodiazepines and other addictive tranquilizers History of pancreatitis, including gallstone related pancreatitis (subsequent to which patient has cholecystectomy) Diagnosis of osteopenia or osteoporosis or currently taking denosumab, romosozumab-aqqg, bisphosphonates or teriparatide Diagnosis of autoimmune connective tissue disorder (e.g. lupus erythematosus, scleroderma) Active or recent (less than 12 months) gastroesophageal reflux disease (GERD) unless treated with H2RAs not PPI. Uncontrolled thyroid disease, including a history of thyroid cancer, hyperthyroidism, or taking thyroid hormone for any reason other than primary hypothyroidism (TSH level must be between 0.4-4) Currently taking prescription antithrombotic therapy (e.g. anticoagulant or antiplatelet agent) within 10 days prior to randomization and/or there is a need or expected need to use during the trial 12 months post implant procedure Currently taking the following medications (within 30 days prior to randomization) and/or there is a need or expected need to use these medications during the trial 12 months post index procedure: Restricted Medications/Supplements Systemic corticosteroids Proton Pump Inhibitor (PPI) Drugs known to affect GI motility (e.g.metoclopramide) Prescription or over-the-counter weight loss medication(s) Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), aspirin, ibuprofen, and other anti-inflammatory medication for study duration Medications known to cause significant weight gain or weight loss (e.g. chemotherapeutics) Supplements that are known or suspected to increase bleeding risk including but not limited to: Gingko biloba Ginseng Vitamins C & E Turmeric St. John's wort Evening primrose oil Feverfew Green Tea Extract Active H. pylori History of Crohn's disease, atresias or untreated stenoses Abnormal pathologies or conditions of the gastrointestinal tract, including ulcers or upper gastrointestinal bleeding conditions within 3 months of randomization Any condition or major illness that places the patient at undue risk by participating in the study, including but not limited to, patients at significant risk for surgery because of potential need for surgery to address adverse events Poor dentition not allowing complete chewing of food Enrolled in another investigational study within 3 months of screening for this study (enrollment in observational studies is permitted) Residing in a location without ready access to study site medical resources Documented weight loss of 5% total body weight (TBW) anytime during the 3 months preceding randomization Positive Fecal Immunochemical Test (FIT) at time of screening History or observation of psychological disorder or behavior which could preclude compliance to the treatment and follow up plan No access to an active telephone and internet service for provision of Follow Up Schedule calls and electronic diary Having donated blood or received a blood transfusion in the 90 days prior to baseline labs. Patients should agree not to donate blood during the study Any condition that increases red cell turnover, such as thalassemia Existence of (>5 cm string test) Pseudomonas aeruginosa, Stenotrophomonas maltophilia and/or Klebsiella pneumoniae serotype K1 and K2 A known sensitivity to nickel or titanium Do not meet the screening criteria for MRI (i.e., MRI unsafe, or MRI conditional but not appropriate for the region of interest) Current use of insulin Patients with history or suspicion of coronary artery disease

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A multi-center, double-blinded, randomized, sham-controlled trial to evaluate the safety and effectiveness of the EndoBarrier System. Patients will be randomized 3 (EndoBarrier):1 (Sham).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EndoBarrier<br>Patients in ARM 1, will receive an upper endoscopy and will be treated with the EndoBarrier Liner | Device: EndoBarrier Liner<br>* The EndoBarrier System is provided as a single-use, sterile device and consists of an EndoBarrier Liner preloaded, packaged and sterilized within the EndoBarrier Delivery System. The EndoBarrier Delivery System is utilized to deliver the EndoBarrier Liner to the proximal small intestine. The EndoBarrier Liner is removed using the EndoBarrier Retrieval System. The EndoBarrier System incorporates no pharmacological, biological tissue or blood products.<br>* Other names: Duodenal-jejunal Bypass Liner (DJBL);|
| Sham Comparator: Sham<br>Patients in Arm 2 will receive an upper endoscopy, but will not be treated with the EndoBarrier Liner. | Other: Sham<br>* Patient receives upper endoscopy but no treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c | Change in HbA1c value from baseline to 12 months. | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c value | Proportion of patients who achieve an HbA1c value of < 7 % by 12 months (52 weeks). | 1 and 2 years | 
| Weight Loss | Proportion of patients who achieve percent total body weight loss ≥ 5% from baseline | 1 and 2 years | 
| Insulin use | Proportion of patients initiating insulin | 1 and 2 years | 
| LDL cholesterol | Change in LDL cholesterol | 1 and 2 years | 
| Triglycerides | Change in triglycerides | 1 and 2 years | 
| Lower risk of CKD progression | Assessment of eGFR | 1 and 2 years | 
| Lower risk of development of CKD | Assessment of eGFR | 1 and 2 years | 
| Change in risk for kidney disease | Combined changes in eGFR and Albuminuria | 1 and 2 years | 
| Blood pressure | Change in systolic blood pressure values | 1 and 2 years | 
| Change in daily fasting glucose level | Change in fasting blood glucose values as measured by daily glucometer reading in mg/dL | 1 and 2 years | 
| Change in Nonalcoholic Fatty Liver Disease (NAFLD) | Change in NAFLD, change in % liver fat using MRI (proton density fat fraction) | 1 and 2 years | 
| Change in Nonalcoholic Steatohepatitis (NASH) | NASH- liver fibrosis % compared to baseline using using MRE measured in kPa | 1 and 2 years | 
| Questionnaire | Change from baseline in treatment satisfaction using Diabetes Treatment Satisfaction Questionnaire (DTSQ) | 1 and 2 years | 
| Questionnaire | Impact of weight on quality of life (IWQOL) | 1 and 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Type 2 Diabetes