Evaluation of the Efficacy and Safety of Duodenal Mucosal Resurfacing Using the Revita® System in Subjects With Type 2 Diabetes on Insulin Therapy (REVITALIZE 1)

• ClinicalTrials.gov Identifier: NCT04419779
• Recruitment Status: Recruiting
• First Posted: June 5, 2020
• Last Update Posted: May 13, 2024
• Sponsor: Fractyl Health Inc.
• Information provided by (Responsible Party): Fractyl Health Inc.

Tracking Information

• First Submitted Date: June 3, 2020
• First Posted Date: June 5, 2020
• Last Update Posted Date: May 13, 2024
• Actual Study Start Date: March 8, 2021
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 2, 2024)

Demonstrate superiority of Revita DMR to sham in improving glycemic control [ Time Frame: Baseline to Week 24 ]

Change from baseline in HbA1c at Week 24

Original Primary Outcome Measures (submitted: June 3, 2020)

Percentage of subjects who achieve a HbA1c ≤ 7.0% at Week 24 without the need for insulin at Week 24, DMR vs Sham. [ Time Frame: 24 Weeks ]

The percentage of patients who achieve a HbA1c ≤ 7.0% at Week 24 without the need for insulin at Week 24, will be analyzed using a logistic regression model with terms for Baseline insulin dose, Baseline HbA1c, Change from Screening to Baseline HbA1c, region (e.g. North America, Europe), Baseline FPG, and Treatment group.

Current Secondary Outcome Measures (submitted: February 2, 2024)

• Demonstrate superiority of Revita DMR to sham in achieving target HbA1c at 24 weeks [ Time Frame: Baseline to Week 24 ]
  The proportion of subjects who achieve an HbA1c of ≤7.0% at Week 24
• Demonstrate superiority of Revita DMR to sham in fasting glucose at 24 weeks [ Time Frame: Baseline to Week 24 ]
  Change from baseline in fasting plasma glucose (FPG) at Week 24
• Demonstrate superiority of Revita DMR to sham in weight loss at 24 weeks [ Time Frame: Baseline to Week 24 ]
  Percentage of total body weight loss (%TBWL) from baseline at Week 24
• Demonstrate superiority of Revita DMR to sham in insulin requirement at 24 weeks [ Time Frame: Baseline to Week 24 ]
  Percentage change from baseline in insulin total daily dose at Week 24
• Demonstrate superiority of Revita DMR to sham in elimination of insulin use at 24 weeks [ Time Frame: Baseline to Week 24 ]
  The proportion of subjects who discontinued insulin at Week 24

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of the Efficacy and Safety of Duodenal Mucosal Resurfacing Using the Revita® System in Subjects With Type 2 Diabetes on Insulin Therapy
• Official Title: A Prospective, Randomized, Double-Blind, Sham-Controlled, Multi-Center Pivotal Study to Evaluate the Efficacy and Safety of Duodenal Mucosal Resurfacing Using the Revita® System in Subjects With Type 2 Diabetes on Insulin Therapy
• Brief Summary: The Revita® system is being investigated to assess the efficacy of DMR versus Sham on improvement in Glycemic, Hepatic and Cardiovascular endpoints for patients with Type 2 Diabetes who are inadequately controlled with insulin therapy. The purpose of this study is to demonstrate the efficacy and safety of the Fractyl DMR Procedure using the Revita® System compared to a sham. Subjects randomized to the DMR procedure will be followed per protocol till 48 weeks post treatment. Subjects in the Sham treatment arm will be offered cross over to receive the DMR treatment at 48 weeks and will be followed per protocol for 48 weeks post treatment.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Type 2 Diabetes

Intervention

• Device: Duodenal Mucosal Resurfacing (DMR)
  The Fractyl DMR Procedure utilizes the Revita® Catheter to perform hydrothermal ablation of the duodenum. The Catheter is delivered trans-orally over a guide-wire to first inject saline to lift the sub-mucosal space, followed by an ablation of the duodenal mucosa. Subjects who receive the DMR treatment are followed for 48 weeks post treatment.
• Device: Duodenal Mucosal Resurfacing (Sham)
  The Sham procedure consists of placing the Revita® Catheter as described above into the duodenum for a minimum of 30 minutes and then removing it from the patient. Subjects who receive the Sham procedure are followed for 48 weeks post treatment and are offered cross over to undergo the DMR procedure at 48 weeks and are followed for further 48 weeks post treatment. Sham subjects who choose not to cross over are discontinued from the study.

Study Arms

• Active Comparator: Duodenal Mucosal Resurfacing (DMR)
  Duodenal Mucosal Resurfacing (DMR) treatment will include hydrothermal ablation of the duodenal muscosa in an upper endoscopic procedure in patients with type 2 diabetes on insulin.
  Intervention: Device: Duodenal Mucosal Resurfacing (DMR)
• Sham Comparator: Duodenal Mucosal Resurfacing Sham (Sham)
  Duodenal Mucosal Resurfacing Sham (Sham) treatment will include an upper endoscopic procedure similar to DMR treatment without hydrothermal ablation of the duodenal mucosa in patients with type 2 diabetes on insulin.
  Intervention: Device: Duodenal Mucosal Resurfacing (Sham)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 2, 2024): 320
• Original Estimated Enrollment (submitted: June 3, 2020): 406
• Estimated Study Completion Date: January 2026
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male, and non-pregnant, non-lactating females
2. Age between 21 and 70 years (both inclusive)

3. Subjects with type 2 diabetes on stable doses of 20-100 units (both inclusive) of total daily insulin dose of basal insulin or basal insulin combined with short-acting insulin and up to 3 permitted non-insulin antidiabetic agents (ADAs). Permitted non-insulin ADAs include:

   • Metformin,
   • Glucagon-like peptide-1 receptor agonist (GLP-1 RA) including dual peptide agonists and related molecules (e.g., glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA),
   • Dipeptidyl peptidase 4 inhibitor (DPP-4i),
   • Thiazolidinediones (TZD),
   • Sodium-glucose cotransporter 2 inhibitors (SGLT2i),
   • Sulfonylureas (SU),
   • Meglitinides
4. Glycosylated hemoglobin A1c (HbA1c) of 7.5-10% (both inclusive)
5. Body mass index (BMI) > 24 to ≤ 40 kg/m^2
6. Women of childbearing potential (WOCBP) should have a negative urine beta human chorionic gonadotrophin (hCG) pregnancy test and must agree to use two established contraceptive methods throughout the study duration.
7. Able to sign an informed consent form and comply with study requirements

Exclusion Criteria:

1. FPG >270 mg/dL
2. Known case of absolute insulin deficiency as indicated by clinical assessment a fasting plasma C-peptide of <0.6 ng/ml
3. Subjects on any other class of glucose-lowering agents other than GLAs listed in inclusion criteria
4. Any drugs or concomitant medications (e.g., psychoactive drugs such as carbamazepine, phenobarbital, sympathomimetics such as ephedrine, corticosteroids, anabolic steroids, and male sex hormones such as testosterone) that can interfere with glucose metabolism
5. Recurrent or severe urinary tract or genital mycotic infections or history of genitourinary infection within 4 weeks prior to informed consent
6. ALT or AST >3 times upper limit normal values
7. Use of an investigational drug within 1 month or 5 half-lives (whichever is longer) before the screening
8. Diagnosed with type 1 diabetes or with a recent history of ketoacidosis
9. Ketosis-prone T2D
10. Known diabetes related non-healing diabetic ulcers or amputations
11. History of more than 1 severe hypoglycemia episode or hypoglycemia unawareness within past 6 months
12. Clinically significant hypoglycemia occurring during the run-in period, defined as a) 2 or more glucose alert values of ≤70 mg/dL (3.9 mmol/L) unless a clear correctable precipitating factor can be identified; b) clinically significant hypoglycemia with self-monitored or laboratory plasma glucose level <54 mg/dL (3.0 mmol/L); c) severe hypoglycemic episode requiring third party assistance
13. Known intestinal autoimmune disease, including celiac disease, ulcerative colitis, Crohn's disease, lupus erythematosus, scleroderma, or other autoimmune connective tissue disorder, which affects the small intestine
14. Secondary hypothyroidism or inadequately controlled primary hypothyroidism (thyroid stimulating hormone [TSH] value outside the normal range at screening)
15. Known history of thyroid cancer or hyperthyroidism with treatment within the past 12 months or inadequately controlled hyperthyroidism
16. An uncontrolled endocrine condition such as multiple endocrine neoplasia (except T2D)
17. Known history of a structural or functional disorder of the esophagus, including any swallowing disorder, esophageal chest pain disorders, drug-refractory esophageal reflux symptoms, or active and uncontrolled gastroesophageal reflux disease (GERD) (grade 3 esophagitis or greater)
18. Known structural or functional disorder of the stomach including gastric ulcer, chronic gastritis, gastric varices, hiatal hernia (a large hiatal hernia or type II and higher paraoesophageal hernia), cancer, or any other disorder of the stomach
19. Previous GI surgery that could affect the ability to treat the duodenum such as subjects who have had a Billroth 2, Roux-en-Y gastric bypass, gastric sleeve or other similar procedures or conditions
20. Known history of chronic pancreatitis or a recent history of acute pancreatitis within the past year
21. Presence of acute or chronic active hepatitis B or C (except if hepatitis C is cured) or cirrhosis; hepatic decompensation/acute liver disease during the last 6 months; or alcoholic or autoimmune chronic hepatitis
22. Symptomatic gallstones, symptomatic kidney stones, or acute cholecystitis
23. Clinically active systemic infection
24. Known immunocompromised status including but not limited to individuals who have undergone organ transplantation, chemotherapy, or radiotherapy within the past 12 months; have clinically significant leukopenia; are positive for the human immunodeficiency virus (HIV); are on potential immunosuppressants; or individuals whose immune status makes the subject a poor candidate for clinical trial participation in the opinion of the Investigator
25. Known active malignancy or partial remission from clinically significant malignancy within the past 5 years (except basal or squamous cell skin cancer, carcinoma in situ, those who received curative treatment and are in complete remission for 5 years, or if the subject is confirmed as cancer free)
26. Known active coagulopathy or current upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, or congenital or acquired intestinal telangiectasia
27. Known cases of anemia, thalassemia, or conditions that affect red blood cell (RBC) turnover such as a recent blood transfusion within 90 days
28. Use of anticoagulation therapy (e.g., warfarin, coumadin, or novel oral anticoagulants such as NOAC) or anti-platelet agents (e.g., thienopyridine) which cannot be discontinued for 5-7 days or 2 drug half-lives before the procedure
29. Use of systemic glucocorticoids (excluding topical or ophthalmic applications or inhaled forms) for more than 10 consecutive days within 90 days prior to the screening visit
30. Use of non-GLA drugs known to affect GI motility (e.g., metoclopramide)
31. Known moderate to severe chronic kidney disease (CKD) with an estimated glomerular filtration rate (eGFR) of <45 mL/min/1.73m2 (estimated by Modification of Diet in Renal Disease [MDRD]), end-stage renal failure, or on dialysis
32. History of myocardial infarction, stroke, transient ischemic attack, coronary artery intervention, CHF exacerbation, or a major event requiring hospitalization within the last 6 months prior to screening
33. History of new or worsening signs or symptoms of coronary heart disease (CHD) within the last 3 months
34. Known case of severe peripheral vascular disease, disease, defined as AMA Criteria Class 1 or greater
35. Known case of symptomatic heart failure with reduced ejection fraction (NYHA Class II-IV) requiring pharmacologic therapy to control symptoms
36. Clinically significant electrocardiogram (ECG) findings such as new clinically significant arrhythmia, ST segment changes, or other conduction disturbances that increase risk of heart disease and require intervention as determined by the investigator
37. Subjects who are at risk of pancreatitis, particularly those with a recent fasting triglyceride value of >600 mg/dL within the past 3 months
38. Actively participating in a weight-loss program and currently not in the maintenance phase
39. General contraindications to deep or conscious sedation, general anesthesia, high risk as determined by anesthesiologist (e.g., ASA score 4 or higher), or contraindications to upper GI endoscopy
40. History of substance use disorder based on the DSM-5 criteria within the last 12 months.
41. Use of weight loss medication such as Meridia, Xenical, over-the-counter weight-loss medications, or other prescribed medications used specifically for the purpose of weight loss
42. Use of dietary supplements or herbal preparations that may have unknown effects on glycemic control or risk of bleeding
43. Participating in another ongoing clinical trial of an investigational drug or device
44. History of non-adherence to treatment in the previous 6 months, as determined by the investigator based on patient history, HbA1c value, or drug accountability
45. Any other mental or physical condition which, in the opinion of the investigator, makes the subject a poor candidate for clinical-trial participation
46. Unwilling or unable to perform SMBG, complete the subject glycemia diary, or comply with study visits and other study procedures as required per protocol
47. Recovered from severe COVID-19 infection (requiring hospitalization) but with persistent long COVID-19 symptoms (i.e., the individual has not recovered for several weeks or months since the start of symptoms that were suggestive of COVID-19, irrespective if the individual is tested or not)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Lynn Wilson; 781-208-2564; lwilson@fractyl.com

Contact: Kelly White; kwhite@fractyl.com

• Listed Location Countries: Belgium, France, Ireland, Italy, Netherlands, Spain, Switzerland, United Kingdom, United States
• Removed Location Countries: Germany

Administrative Information

• NCT Number: NCT04419779
• Other Study ID Numbers: C-00044
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Fractyl Health Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Fractyl Health Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Fractyl Health Inc.
• Verification Date: May 2024