Study on GS300 on NAFLD (REVERT)

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Assessing the Effect of GS300 on Nonalcoholic Fatty Liver Disease

To determine the efficacy of GS300 when administered for 24 weeks in patients with Nonalcoholic Fatty Liver Disease (NAFLD).

Study Overview

• Status: Not yet recruiting
• Conditions: Weight Loss; Nonalcoholic Fatty Liver
• Intervention / Treatment: Device: GS300; Device: Placebo

Detailed Description

This is a multicenter, randomized, placebo-controlled, double-blinded, parallel-group study. Patients will be randomized 1:1 to receive either GS300 or placebo. The study includes an up to 6 weeks screening period, a 24-week treatment period, and a 1-week follow-up period.

Approximately 250 patients (125 patients per arm) will be enrolled (at least 40% from each gender and at least 40% from US and 40% from Europe).

• Study Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Valerie Colletta; Phone Number: 1-857-201-5330; Email: vcolletta@gelesis.com
• Study Contact Backup: Name: Henry Calderon; Phone Number: 1-857-201-5330; Email: hcalderon@gelesis.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 22 years and ≤ 65 years
2. Body Mass Index (BMI) ≥ 27 and ≤ 40 kilogram (kg)/meter2 (m2)
3. Negative for Hepatitis B, C and Human Immunodeficiency Virus (HIV) within 6 months of screening [HbsAg negative and Hepatitis C Virus (HCV) RNA negative; subjects treated and cured of HCV must have completed treatment and tested negative for HCV at least 2 years prior to study enrollment]
4. Fibroscan CAP score > 300 decibels (dB)/m
5. Stable body weight defined as less than 5% change in body weight in the 3 months prior to screening (per patient report)

6. Approximately 250 patients (approximately 125 patients per treatment arm)

   1. Prediabetes i) Untreated prediabetic patients with FPG ≥ 100 mg/ dL (≥ 5.6 mmol/L) and < 126 mg/dL (< 7.0 mmol/L) at both Screening Visits with HbA1c ≤ 6.4% (≤ 46 mmol/mol) - if only one value is within this range, the other value should not be ≥ 126 mg/dL (≥ 7.0 mmol/L) and HbA1c should be ≥ 5.7% (≥ 39 mmol/mol) and ≤ 6.4% (≤ 46 mmol/mol) ii) Drug-treated (metformin) prediabetic patients with FPG ≥ 70 mg/dL (≥ 3.9 mmol/L) and < 126 mg/dL (< 7.0 mmol/L) at both Screening Visits
   2. Type 2 Diabetes i) Untreated type 2 diabetic patients with FPG ≤ 200 mg/dL (≤ 11.2 mmol/L) at both Screening Visits and either FPG ≥ 126 mg/dL (≥ 7.0 mmol/L) at both Screening Visits or FPG < 126 mg/dL (< 7.0 mmol/L) at one or both Screening Visits with HbA1c ≥ 6.5% (≥ 48 mmol/mol) ii) Drug-treated [metformin and/or dipeptidyl peptidase-4 (DPP-4) inhibitors, and/or insulin] type 2 diabetic patients with FPG ≥ 70 mg/dL (≥ 3.9 mmol/L) and ≤ 270 mg/dL (≤ 15.1 mmol/L) at both Screening Visits Note, approximately 10% to 20% of enrolled Type 2 diabetic patients will be on insulin therapy
   3. Normoglycemia (up to approximately 10% of patients) Normoglycemic patients with FPG ≥ 70 mg/dL (≥ 3.9 mmol/L) and < 100 mg/ dL (< 5.6 mmol/L) at both Screening Visits with HbA1c < 5.7% (< 39 mmol/mol) and HOMA-IR ≥ 3.0
7. MRI PDFF ≥ 10%
8. Willing to sign the ICF prior to any study related procedures

Exclusion Criteria:

1. Self-reported alcohol intake > 20 gram (g)/day for women and > 30 g/day for men (on average per day) as per medical history
2. Alcohol Use Disorders Identification Test (AUDIT) questionnaire: AUDIT-C score of ≥ 4 in men and ≥ 3 in women will be followed by a full AUDIT questionnaire by interview with patients excluded for score ≥ 8
3. Prior liver transplant

4. Liver cirrhosis as evidenced by any of the following:

   • Serum albumin < 3.5 g/dL (0.53 mmol/L)
   • INR > 1.3 (unless due to anticoagulant therapy)
   • AST/ALT ratio ≥ 2
   • Direct bilirubin > 0.3 mg/dL (5.13 micromol (micromol)/L)
   • Platelet count < 150,000/microL

5. History or evidence of other chronic liver diseases, including, but not limited to the following:

   • Current active autoimmune hepatitis
   • Primary biliary cholangitis (PBC)
   • Primary sclerosing cholangitis
   • Wilson's disease
   • Alpha-1-antitrypsin (A1AT) deficiency
   • Hemochromatosis
   • Drug-induced liver disease, as defined on the basis of typical exposure and history
   • Bile duct obstruction
   • Suspected or proven liver cancer
   • History of hepatic encephalopathy
   • Portal hypertension (esophageal varices, ascites, splenomegaly)
6. History of gastric surgery (up to 10% patients with history of gastric bypass or sleeve gastrectomy may be enrolled if the surgery occurred more than 6 months prior to enrollment and patients had a weight change < 5% during the 3 months prior to enrollment)
7. Angina, coronary bypass, or myocardial infarction within 6 months prior to Screening Visit
8. Inflammatory bowel disease, celiac disease, or other significant gastrointestinal disease - for example, a history of bowel obstruction without surgical correction (patients with irritable bowel syndrome may be enrolled)
9. Pregnancy
10. Absence of medically approved contraceptive methods in females of childbearing potential (e.g., hysterectomy, oral contraceptives, non-oral contraceptive medications or intrauterine device combined with a barrier method, two combined barrier methods such as diaphragm and condom or spermicide, or condom and spermicide; bilateral tubal ligation and vasectomy are not acceptable methods)
11. Type 1 Diabetes
12. HbA1c > 8.5% (> 69 mmol/mol)
13. Serum LDL-C ≥ 160 mg/dL (≥ 4.15 mmol/L)
14. Serum triglycerides ≥ 350 mg/dL (≥ 3.96 mmol/L)
15. Use of any medications for the treatment of diabetes within 3 months prior to enrollment. Note, metformin, DPP-4 inhibitors, and insulin at a stable dose over the last 3 months are allowed. Insulin dose variance of 20% (decrease or increase) is allowed.

16. Any change in standard of care or background therapy for liver disease or other ongoing chronic conditions within 3 months prior to enrollment, including changes in the following:

    • Antidiabetic medications (metformin, DPP-4 inhibitors, insulin)
    • Thyroid hormones
    • Medications treating depression
    • Medications treating dyslipidemia
    • Medications treating hypertension
    • Vitamin E

17. Regular/daily use of any of the following within 3 months prior to enrollment or anticipated regular/daily use during the study period:

    • High dose nonsteroidal anti-inflammatory drugs (NSAIDS) (equivalent of > 3,200 mg/day ibuprofen)
    • Systemic corticosteroids, anabolic steroids
    • Methotrexate, amiodarone, tamoxifen, tetracyclines, estrogens at doses greater than those used for hormone replacement, valproic acid
    • Probiotic supplements (yogurt is allowed)
    • Addictive, non-prescribed medications including amphetamines, barbiturates, cocaine, opiates, methadone and phencyclidine as per medical history or regular daily use of cannabinoids
18. Use of any anti-obesity medications (including herbal preparations) within 2 months prior to enrollment or any anticipated use during the study period
19. History of allergic reaction to carboxymethylcellulose (CMC), citric acid, sodium stearyl fumarate, raw cane sugar, gelatin, or titanium dioxide
20. Currently enrolled in another investigational device or drug study, or less than 3 months since ending another investigational device or drug study(s), or receiving other investigational treatment(s)
21. Any disease or condition that, in the opinion of the investigator or Sponsor, would interfere with study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Active; GS300: Three (3) GS300 capsules [approximately 0.65 grams (g)] two (2) times per day ingested 10 minutes (min) before meals (i.e., lunch and dinner) - total of 3.9 g per day	Device: GS300; Gelesis300 hydrogel in gelatin capsules
PLACEBO_COMPARATOR: Placebo; Placebo: Three (3) placebo capsules two (2) times per day 10 min before meals (i.e., lunch and dinner)	Device: Placebo; Placebo capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight loss ≥ 5%	Proportion of patients with weight loss ≥ 5% at Week 24.	24 Weeks
Placebo-adjusted percent change in weight from Baseline to Week 24	Placebo-adjusted percent change in weight from Baseline to Week 24.	24 Weeks
Relative reduction in liver fat	Relative reduction in liver fat from Baseline to Week 24, as measured by hepatic Magnetic Resonance Imaging Proton Density Fat Fraction (MRI PDFF).	24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight loss ≥ 7.5%	To assess reduction in weight (≥ 7.5%) in patients with NAFLD treated with GS300 or placebo.	24 Weeks
Weight loss ≥ 10%	To assess reduction in weight (≥ 10%) in patients with NAFLD treated with GS300 or placebo.	24 Weeks
To evaluate the percentage of patients with ≥ 30% relative reduction in liver fat	To evaluate the percentage of patients with ≥ 30% relative reduction in liver fat in patients treated with GS300 or placebo.	24 Weeks
To assess placebo-adjusted waist circumference reduction	To assess placebo-adjusted waist circumference reduction after 24 weeks of treatment with GS300 or placebo.	24 Weeks
To assess the impact of GS300 on glycemic control in patients with NAFLD	To assess the impact of GS300 on glycemic control in patients with NAFLD treated with GS300 or placebo.	24 Weeks
To assess the impact of GS300 on liver enzymes in patients with NAFLD	To assess the impact of GS300 on liver enzymes in patients with NAFLD treated with GS300 or placebo.	24 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intestinal Permeability	Intestinal permeability - Urine test (sub-population of 50 patients at selected sites).	24 Weeks
Vitamin Levels	Serum/plasma vitamin levels (sub-population at selected sites).	24 Weeks
Gut Peptides	Glucagon-like Peptide-1 (GLP-1), Glucagon-like Peptide-2 (GLP-2), Gastric Inhibitory Polypeptide (GIP), ghrelin, somatostatin, Cholecystokinin (CCK), Peptide YY (PYY).	24 Weeks

Collaborators and Investigators

• Sponsor: Gelesis, Inc.
• Investigators: Study Director: Hassan M Heshmati, MD, Gelesis, Inc.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 1, 2022
• Primary Completion (ANTICIPATED): December 31, 2023
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: May 11, 2021
• First Submitted That Met QC Criteria: May 11, 2021
• First Posted (ACTUAL): May 14, 2021

Study Record Updates

• Last Update Posted (ACTUAL): January 24, 2022
• Last Update Submitted That Met QC Criteria: January 21, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Body Weight; Body Weight Changes; Fatty Liver; Weight Loss; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: GS-300-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No