A Prospective, Randomized, Double-Blind, Sham-Controlled, Multicenter, Pivotal Study to Assess the Efficacy of Revita® Duodenal Mucosal Resurfacing (DMR) on Body Weight Maintenance in Participants With Obesity and Who Have Achieved at Least 15% Weight Loss on Tirzepatide Obesity Pharmacotherapy
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 315
- 试验地点
- 37
- 主要终点
- To demonstrate that Revita DMR is superior to sham in percent change in body weight from baseline to week 26
研究概览
简要总结
Fractyl is evaluating Revita Duodenal Mucosal Resurfacing (DMR) in the REMAIN-1 pivotal study, which is designed to include two cohorts - an open label cohort referred to as REVEAL-1, and a randomized cohort, which includes both a midpoint analysis and a pivotal analysis. Patients who previously lost at least 15% of their body weight on a GLP-1 can qualify for the open label REVEAL-1 cohort. The data generated from the REVEAL-1 cohort will be used for open label reporting as the study progresses. The REMAIN-1 randomized cohort will enroll patients living with obesity and a body mass index ("BMI") between 30 and 45 kg/m2 who are not currently on a GLP-1 drug. Patients will be prescribed tirzepatide and titrated to achieve at least 15% total body weight loss, at which time tirzepatide will be discontinued and patients will be randomized to Revita versus sham at 2:1.
Midpoint Analysis of Randomized Cohort:
The midpoint analysis of the randomized cohort will be performed at three months of follow-up on approximately 45 patients, allowing us to assess and report on safety and efficacy signals that could be anticipated in the pivotal analysis. These patients are distinct from those included in the pivotal analysis.
Pivotal Analysis of Randomized Cohort:
The pivotal analysis of the randomized cohort will be performed on approximately 315 patients (distinct from those included in the midpoint analysis) and will evaluate safety and efficacy in the first co-primary endpoint, which is weight regain from the time of tirzepatide discontinuation in Revita DMR versus sham patients at six months, with a primary objective of demonstrating a benefit of Revita DMR versus sham for weight maintenance after GLP-1 discontinuation. The second co-primary endpoint evaluates a responder rate among the Revita DMR treated group at one year to demonstrate the durability of the Revita DMR procedure for weight maintenance after discontinuation of a GLP-1-based therapy.
Secondary objectives will include evaluation of the effectiveness of the Revita DMR procedure on the change in blood glucose levels, cardiovascular disease ("CVD") risk factors, body composition and pre-diabetes status. All patients enrolled in the study will receive diet and lifestyle counseling.
详细描述
Title A Prospective, Randomized, Double-Blind, Sham-Controlled, Multicenter, Pivotal Study to Assess the Efficacy of Revita® Duodenal Mucosal Resurfacing (DMR) on Body Weight Maintenance in Participants with Obesity Who Have Achieved at Least 15% Weight Loss on GLP-1 Based Pharmacotherapy (REMAIN-1)
Short Title Revita® Duodenal Mucosal Resurfacing for Weight Maintenance (REMAIN-1)
Protocol Number C-00700 Study Population Male and non-pregnant non-lactating females aged 21 -70 years, who do not have type 1 or type 2 diabetes mellitus, and with a body mass index (BMI) ≥ 30 kg/m2 Trial Design Study C-00700 is a multi-Stage study which may be conducted in parallel.
Stage 1 is an open-label training Stage enrolling participants already on GLP-1 based therapy (prior to study enrollment) with at least 15% total body weight loss (TBWL) since initiation of the GLP-1 based drug. Those participants who lost at least 15% total body weight on the GLP-1 based drug and wish to discontinue the use, will be eligible to receive Revita DMR procedure.
An open-label training Stage (Stage 1) will require treating endoscopy sites without prior experience with Revita DMR to perform DMR in up to 4 participants per site prior to treating any participant in the randomization Stage (Stage 2) to ensure consistency of study procedures prior to initiating randomization. Sites with prior Revita DMR training and experience may, but are not required to, enroll participants from this stage in parallel to Stage 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
Both the obesity research center team (obesity specialist/endocrinologist, blinded study coordinator, obesity research study staff) and the study participant are blinded to the treatment through the 48-week follow-up visit. The Sponsor (except for unblinded Sponsor personnel [see below]) is blinded to the treatment through the 24-week follow-up visit.
入排标准
- 年龄范围
- 21 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant-provided, written informed consent to participate in the study in accordance with local regulations
- •Adult participants aged 21-70 years, inclusive
- •Prior to tirzepatide therapy, have a BMI of ≥ 30 kg/m2 (obesity) and ≤ 45 kg/m
- •Have achieved at least 15% weight loss on tirzepatide therapy at Visit 7 (Participants in Stage 1, who enter the study on tirzepatide, must have a documented pre-tirzepatide weight confirming they have lost at least 15% body weight on tirzepatide)
- •Have a history of at least 1 self-reported, unsuccessful, dietary effort to lose body weight
- •All female participants of childbearing potential must have a negative urine pregnancy test at screening and a negative urine pregnancy test at study visit 7 prior to study intervention. Postmenopausal females with amenorrhea for at least 2 years will be eligible if they are > 50 years of age. Postmenopausal females with amenorrhea for at least 2 years, who are ≤ 50 years, must also have documented serum follicle stimulating hormone levels > 35 mUI/mL
- •Able to walk at least 400 yards (roughly the distance of a track) and climb a flight of stairs without difficulty due to either musculoskeletal injuries/diseases or cardiopulmonary diseases
- •If sexually active, WOCBP must use one of the following birth control methods during the entire course of the study as specified:
- •Intrauterine device in place for at least 3 months before the first dose of tirzepatide and throughout the study
- •Barrier method (condom, diaphragm) with spermicide for at least 14 days before the first dose of tirzepatide and throughout the study
- •Surgical sterilization of the male partner(s) (vasectomy for at least 6 months before first dose of tirzepatide) or
- •Hormonal contraceptives with a barrier method for at least 3 months before the first dose of tirzepatide and throughout the study
排除标准
- •Medical conditions that contraindicate the use of tirzepatide for weight management, as detailed in the tirzepatide prescribing information
- •BMI ≥ 40 kg/m2 at Visit 7
- •Females who are or intend to be pregnant or breastfeeding during the study
- •Known serious hypersensitivity to tirzepatide or any of the excipients in tirzepatide
- •History of infectious liver disease excluding recovered Hepatitis A infection
- •History of pancreatitis within 6 months of screening or any prior history of recurrent pancreatitis (i.e., two or more episodes of pancreatitis)
- •Potentially unreliable participants or those judged by the investigator to be unsuitable for the study
- •Unable or unwilling to follow the dietary restrictions specified by the clinical protocol
- •Known history of or active binge eating disorder or suspected binge eating disorder based on binge eating disorder assessment questionnaire
- •Known history of or active substance abuse including alcohol within the past 2 years that, in the opinion of the investigator, may preclude the participant from following the protocol and completing the study
- •Have history of use of marijuana or tetrahydrocannabinol (THC)-containing products within 3 months of screening or unwillingness to abstain from marijuana or THC-containing products use during the study
- •Diabetes-related conditions:
- •History of type 1 or type 2 diabetes (T2D) or screening values consistent with T2D, or history of any genetic form of diabetes
- •HbA1c > 6.5% or fasting glucose > 125 mg/dL consistent with T2D diagnosis according to the American Diabetes Association Standards of Care 2024 (Participants with isolated impaired fasting glucose [100 to 125 mg/dL, inclusive] may enroll in the study)
- •Laboratory values or clinical abnormalities:
- •Estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73m2 at screening, as assessed by serum creatinine using the revised 2021 CKD-EPI equation
- •Serum calcitonin level ≥ 20 ng/L at screening if eGFR ≥ 60 mL/min/1.73m2 or serum calcitonin level ≥ 35 ng/L if eGFR < 60 mL/min/1.73m2
- •Fasting triglycerides > 500 mg/dL (> 5.6 mmol/L)
- •Abnormal liver function at screening, defined as any of the following: aspartate aminotransferase (AST) > 3X upper limit of the normal reference range (ULN), ALT > 3X ULN, or serum total bilirubin (TB) > 3X ULN
- •Values of systolic blood pressure (SBP) > 180 mmHg and/or diastolic blood pressure (DBP) > 110 mmHg
- •Any ECG or clinical laboratory abnormality which precludes safe involvement in the study in the opinion of the investigator Gastrointestinal
- •Known structural or functional disorder of the esophagus including any swallowing disorder, esophageal chest pain disorders, drug-refractory esophageal reflux symptoms, or active and uncontrolled GERD defined as Los Angeles Grade C or D esophagitis
- •Known structural or functional disorder of the stomach including active 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
- •Clinically significant gastric-emptying abnormality (i.e., severe gastroparesis or gastric outlet obstruction) including a drug-induced abnormality or an abnormality experienced in a person who chronically takes drugs that directly affect GI motility such as metoclopromide or erythromycin
- •Previous GI surgery to treat the duodenum such as participants who have had a Billroth 2, Roux-en-Y gastric bypass, gastric sleeve, or other similar procedures or conditions
- •Known intestinal autoimmune disease including celiac disease, ulcerative colitis, Crohn's disease, lupus erythematosus, scleroderma, or other autoimmune or connective tissue disorder that affects the small intestine
- •Any history of or current other gastrointestinal condition which would preclude an upper GI endoscopy in the opinion of the investigator Cardiovascular
- •New York Heart Association Class III or IV heart failure within 3 months prior to screening
- •History of myocardial infarction or stroke within 6 months of screening
- •Unstable symptomatic or life-threatening arrhythmia or heart block. Note: Asymptomatic atrial fibrillation is not considered to be life-threatening, and patients with asymptomatic atrial fibrillation will be permitted to enter the study
- •Related to other concomitant conditions or medical history:
- •Any concurrent medical condition/disorder or clinically symptomatic cardiovascular, gastrointestinal (including pancreatitis), hematological, pulmonary, psychiatric, acute or chronic infectious disease, active retinal disease or other disorder which, in the investigator's opinion, would interfere with the participant's ability to complete the trial, require administration of treatment that could affect the interpretation of the efficacy or safety variables, or preclude safe involvement in the study
- •Self-reported weight gain > 5 kg within 3 months prior to screening
- •Family history or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia (MEN) syndrome 2
- •History of an active or untreated malignancy or in remission from a clinically significant malignancy within the last 5 years (except for treated basal cell or squamous small cell carcinoma of the skin with no evidence of recurrence)
- •Secondary hypothyroidism or inadequately controlled primary hypothyroidism (thyroid-stimulating hormone [TSH] value outside the range of 0.4 to 6.0 mIU/L at screening)
- •Known thyroid cancer
- •Any uncontrolled endocrine condition such as multiple endocrine neoplasia
- •History of hemoglobinopathies (sickle cell anemia, thalassemia major, sideroblastic anemia) or other blood disorder
- •Any uncontrolled psychiatric disorder as assessed by the investigator
- •Any history of known genetic cause of obesity such as Prader-Willi Syndrome
- •History of COVID infection with prolonged symptoms for >4 weeks
- •Related to past or current medication use:
- •Administration of any investigational drug or participation in an interventional clinical research study within 30 days or 5 half-lives (whichever is longer) of screening visit
- •Use of any oral or injectable hypoglycemic agents or any other prescription or over-the-counter diabetes or weight loss medications within 12 months prior to screening visit, (except in the case of tirzepatide use in the stage 1 training arm of the study only)
- •Use of any other medications known to cause weight gain or weight loss in the opinion of the investigator
- •Receiving or have received, within 3 months prior to screening, chronic (>14 days) systemic (excluding inhaled, intraocular, intra-articular or topical) corticosteroid treatment or likely to require (in the opinion of the investigator) concurrent treatment with corticosteroids (excluding inhaled, intraocular, intra-articular or topical) during the course of the study
- •Treatment with antihypertensive or lipid-modifying medications which are not on a stable dose for at least 8 weeks prior to screening or anticipated changes or dose adjustments within 30 days following randomization into the study
- •Treatment with thyroid hormones which are not on a stable dose for at least 8 weeks prior to screening
- •Use of anticoagulation therapy (e.g., warfarin, coumadin, or novel oral anticoagulants [NOACs]) or anti-platelet agents (e.g., thienopyridine) which cannot be discontinued for 5-7 days or 2 drug half-lives before the procedure Other Exclusions
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研究组 & 干预措施
Training
Sites will gain experience with the study protocol and the Revita DMR procedure in an open-label, single-arm treatment assignment for participants who previously achieved 15% weight loss using a GLP-1
干预措施: Revita Duodenal Mucosal Resurfacing (DMR) (Device)
Active
Patients who have achieved >15% weight loss from baseline will receive the Revita DMR Procedure
干预措施: Revita Duodenal Mucosal Resurfacing (DMR) (Device)
Sham
Patients who have achieved >15% weight loss from baseline will receive and endoscopic evaluation and will have a catheter introduced but the Revita DMR procedure will not be performed
干预措施: Sham (Device)
结局指标
主要结局
To demonstrate that Revita DMR is superior to sham in percent change in body weight from baseline to week 26
时间窗: 26 Weeks
Percent change in total body weight from baseline to week 26, DMR vs sham
To demonstrate that a majority of Revita DMR participants maintain clinically significant weight loss 52 weeks (1 year) after discontinuing tirzepatide therapy
时间窗: 52 weeks
Percentage of DMR participants who maintain at least 5% total body weight loss from pre-tirzepatide (week -21) to week 52
次要结局
- To demonstrate durability of DMR(26 & 52 weeks)
- To demonstrate DMR in comparison to sham in change from baseline for total body weight change(52 Weeks)
- To demonstrate DMR in comparison to sham in change from baseline for fating C-peptide(26 & 52 Weeks)
- To demonstrate DMR in comparison to sham in change from baseline for metabolic health(26 & 52 Weeks)
- To evaluate dimensions of upper gastrointestinal distress throughout the study (tirzepatide open-label run in vs. after randomization)(26 & 52 Weeks)