Evaluation of the Safety and Efficacy of Revita® DMR on Body Weight Maintenance in Subjects With Obesity Who Have Achieved at Least 15% Weight Loss on Tirzepatide
NCT Number: NCT06484114
Acronym: REMAIN-1
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Obesity|Weight Change Trajectory|Weight Change, Body
Interventions: DEVICE: Revita Duodenal Mucosal Resurfacing (DMR)|DEVICE: Sham
Sponsor: Fractyl Health Inc.
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 315
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (PARTICIPANT, CARE_PROVIDER, OUTCOMES_ASSESSOR)|Primary Purpose: PREVENTION
Start Date: 2024-09-01
Completion Date: 2027-09-30

Summary:
The REMAIN-1 clinical trial is a prospective, pivotal, double-blind, randomized, sham-controlled trial that will investigate the superiority of Revita DMR compared with sham on the maintenance of weight loss after successfully losing at least 15% total body weight on an open-label, dose escalation, tirzepatide run-in period of approximately 16-20 weeks. Study participants are male and non-pregnant, non-lactating females, aged 21 -70 years, who do not have type 1 or type 2 diabetes mellitus, with a BMI ≥30 kg/m2. The REMAIN-1 study will consist of 4 periods:

* A screening period of 1 week
* An approximately 16-20-week, dose-escalation, tirzepatide run-in period
* A double-blind intervention period: A 2:1 (DMR: sham) randomization with 48 weeks of blinded post-intervention follow up

An upper limit of 75% enrollment of females will be used to ensure a sufficiently large sample of males.

REMAIN-1 will be a multicenter trial in the United States with up to 35 Revita treatment centers that have experience in advanced endoscopy procedures and metabolic obesity treatment. Approximately 315 participants will be randomized to DMR (n=210) or sham (n=105) treatment. The Revita® System is an endoscopic treatment consisting of a single catheter and console designed to lift the duodenal mucosa with saline followed by controlled circumferential hydrothermal ablation of the mucosa. The sham procedure consists of placing the Revita Catheter described above into the duodenum for a minimum of 30 minutes with no manipulation of the device or activation of the catheter.

An interim analysis of the primary endpoint will be performed after at least 75% of participants have been randomized. The conditional power (CP) will be calculated using accumulated trial data at the time of the interim analysis.

The study is centrally randomized, and assignment to treatment groups will be determined by a computer-generated random sequence. Randomization will be stratified by sex (male, female) and BMI (\<30 or ≥30 kg/m2).

An open-label training stage of the study (stage 1) will precede the randomized stage (stage 2) at study sites. The training stage will provide additional safety and efficacy information on DMR in the maintenance of weight loss after DMR in participants who have successfully lost at least 15% total body weight during the tirzepatide run-in period or have already lost a clinically relevant amount of weight (at least 15% total body weight) on tirzepatide (prior to study entry) and wish to discontinue therapy for a variety of reasons including cost, insurance coverage, side effects and patient preference.

Primary Outcome Measures: To demonstrate that Revita DMR is superior to sham in percent change in body weight from baseline to week 24, Percent change in total body weight from baseline to week 24, DMR vs sham, 24 Weeks|To demonstrate that a majority of Revita DMR participants maintain clinically significant weight loss after discontinuing tirzepatide therapy, Percentage of DMR participants who maintain at least 5% total body weight loss from pre-tirzepatide (week -21) to week 24, 24 weeks
Secondary Outcome Measures: To demonstrate that Revita DMR is superior to sham in the percent change in body weight, pre-tirzepatide to week 24 post-study intervention, Percent change in total body weight from pre-tirzepatide (week -21) to week 24, DMR vs sham, 24 weeks|To demonstrate that Revita DMR is superior to sham in the prevention of weight regain following tirzepatide discontinuation and 24 weeks post-study intervention, Percentage of participants who maintain at least 10% total body weight loss from pre-tirzepatide (week -21) to week 24, DMR vs sham, 24 weeks