A Study of FT 4101 in Overweight/Obese Participants With Non-alcoholic Steatohepatitis

NCT04004325 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 4101-MET-201
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

This Phase 1/2 study will evaluate safety, efficacy, PK, and PD of FT-4101 as a single agent in overweight/obese subjects with NASH. The study may be conducted in up to 2 dosing cohorts.

Conditions

Nonalcoholic Steatohepatitis (NASH); Overweight or Obesity

Outcome Measures

Primary Outcomes (15)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  TEAEs were defined as an adverse events (AEs) with an onset that occurred after receiving the first dose of the study drug (AE start date greater than or equal to \[\>=\] first dose date) and within 30 days after receiving the last dose of the study drug (AE start date - last dose date less than or equal to \[\<=\] 30). Number of participants with TEAEs are reported.

  From start of study drug administration up to 20 weeks

• Number of Participants With Clinically Significant Changes in Laboratory Values

  Number of participants with clinically significant changes in laboratory values (hematology, serum chemistry, and urinalysis) are reported.

  Up to 20 weeks

• Number of Participants With Clinically Significant Changes in Physical Examination

  Number of participants with clinically significant changes in physical examination are reported.

  Up to 20 weeks

• Change From Baseline in Vital Signs: Blood Pressure (BP)

  Change from baseline in blood pressure (systolic and diastolic) are reported.

  Baseline, Day 92

• Change From Baseline in Vital Signs: Heart Rate (HR)

  Change from baseline in heart rate is reported.

  Baseline, Day 92

• Change From Baseline in Vital Signs: Respiratory Rate

  Change from baseline in respiratory rate is reported.

  Baseline, Day 92

• Change From Baseline in Vital Signs: Temperature

  Change from baseline in temperature is reported.

  Baseline, Day 92

• Change From Baseline in 12-lead Electrocardiogram (ECG) Parameters: ECG Mean Heart Rate

  Change from baseline in ECG mean heart rate is reported.

  Baseline, Day 92

• Change From Baseline in 12-lead ECG Parameters: QT Interval

  Change from baseline in QT interval is reported.

  Baseline, Day 92

• Change From Baseline in 12-lead ECG Parameters: PR Interval

  Change from baseline in PR interval is reported.

  Baseline, Day 92

• Change From Baseline in 12-lead ECG Parameters: QRS Interval

  Change from baseline in QRS interval is reported.

  Baseline, Day 92

• Change From Baseline in 12-lead ECG Parameters: RR Interval

  Change from baseline in RR interval is reported.

  Baseline, Day 92

• Change From Baseline in 12-lead ECG Parameters: QTc (Corrected) Using the Fridericia Correction (QTcF) Interval

  Change from baseline in QTcF interval is reported.

  Baseline, Day 92

• Percent Change From Baseline in Liver Fat on Magnetic Resonance Imaging- Proton Density Fat Fraction (MRI-PDFF)

  Percent change from baseline in liver fat on MRI-PDFF is reported.

  At week 12

• Change From Baseline in Liver Fat on Magnetic Resonance Imaging- Proton Density Fat Fraction (MRI-PDFF)

  Change from baseline in percentage of liver fat on MRI-PDFF is reported.

  At week 12

Secondary Outcomes (11)

• Change From Baseline in Liver Fat on MRI-PDFF

  At week 6

• Percent Change From Baseline in Liver Fat on MRI-PDFF

  At week 6

• Percentage of Participants Experiencing a Relative Reduction of 30% or Greater of Liver Fat as Assessed by MRI-PDFF

  At week 12

• Change From Baseline in Alanine Aminotransferase (ALT)

  Baseline, Day 92

• Change From Baseline in Aspartate Aminotransferase (AST)

  Baseline, Day 92

Study Arms (2)

Cohort A

EXPERIMENTAL

Drug: FT-4101; Drug: FT-4101 placebo; Other: Deuterated Water

Cohort B

EXPERIMENTAL

Drug: FT-4101; Drug: FT-4101 placebo; Other: Deuterated Water

Interventions

FT-4101 DRUG

FT-4101 will be supplied as active capsules and will be administered per the protocol defined frequency and dose level.

Cohort A; Cohort B

FT-4101 placebo DRUG

FT-4101 placebo will be supplied as placebo capsule matching in size and color to all the active capsules and will be administered per the protocol defined frequency and dose level.

Cohort A; Cohort B

Deuterated Water OTHER

Deuterated water will be provided as individual ready-to-use, single dose bottles each containing 50 mL of deuterated water (70%).

Cohort A; Cohort B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meets all of the following criteria:
• CAP ≥ 300 dB/m by FibroScan® OR Liver biopsy within 24 months, consistent with NASH with stage 2-3 fibrosis
• Screening MRI-PDFF with ≥ 10% steatosis.
• Body mass index (BMI) \> 25.0 to \< 45.0 kg/m2
• Stable body weight
• Subjects with T2DM may also be included, if:
• Subject with T2DM is on stable doses of metformin monotherapy (subjects on combination therapy of metformin and sulfonylurea (SU) need to undergo washout period prior to dosing) with no changes in medication within the previous 6 months
• HbA1c \< 9% (one retest is permitted with the result of the last test being conclusive)
• Fasting plasma glucose (FPG) \< 240 mg/dL (\<13.3 mmol/L)
• Waist circumference ≤ 57 inches
• Female subjects must be non-pregnant and non-lactating

You may not qualify if:

• Type 1 diabetes and type 2 diabetic subjects on insulin therapy
• Diabetic complications, such as acute proliferative retinopathy
• Recurrent severe hypoglycemia or hypoglycemic unawareness or recent severe ketoacidosis
• History of, or active, chronic liver disease due to alcohol, auto-immune, primary biliary cholangitis, HIV, HBV or active HCV-infection, Wilson's, α-1-antitrypsin deficiency, hemochromatosis, etc., and not due to NASH disease
• History of clinically significant or decompensated chronic liver disease including esophageal varices, ascites, encephalopathy or any hospitalization for treatment of chronic liver disease; or MELD score ≥ 10.
• History of significant cirrhosis of the liver
• Alcohol consumption greater than 14 drinks per week for men or greater than 7 drinks per week for women and/or positive alcohol breath test
• Introduction of an anti-obesity drug in the past 6 months prior to screening
• History of gastrointestinal malabsorptive bariatric surgery, any other gastrointestinal surgery that may induce malabsorption, history of bowel resection \> 20 cm, any malabsorption disorder, severe gastroparesis, any GI procedure for weight loss, as well as clinically significant gastrointestinal disorders within less than 5 years
• Ingestion of drugs known to produce hepatic steatosis including corticosteroids, high- dose estrogens, methotrexate, tetracycline or amiodarone in the previous 6 months
• History of, or current cardiac dysrhythmias and/or a history of cardiovascular disease events, including congestive heart failure, unstable coronary artery disease, myocardial infarction
• Significant systemic or major illnesses other than liver disease, including cerebrovascular disease, pulmonary disease, renal failure, organ transplantation, serious psychiatric disease, malignancy that, in the opinion of the investigator, would preclude treatment with FT-4101 and/or adequate follow up
• History of chronic skin conditions such as psoriasis, eczema or any recurring rash/dermatitis requiring oral or topical corticosteroids or other topical applications within 12 months
• Hair loss or unexplained alopecia within 12 months
• History of chronic eye conditions, Sjögren syndrome or any history of dry eyes or allergic conjunctivitis requiring artificial tears or medicated eye drops or previous refractive surgery within 12 months (Subjects with dry eyes due to wearing contact lenses are eligible)

Sponsors & Collaborators

• Forma Therapeutics, Inc.: lead
• ProSciento, Inc.: collaborator

Study Sites (2)

ProSciento, Inc.

Chula Vista, California, 91911, United States

Location

Catalina Research Institute

Montclair, California, 91763, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Overweight; Obesity

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The study was planned for two dosing cohorts (Cohort A and Cohort B), but only Cohort A was included. The study terminated because of observed insufficient efficacy with the studied dose to warrant further investigation. The 3 mg dose didn't raise safety concerns, but to achieve a meaningful result, higher doses would exceed the safe limit based on past studies. Therefore, it was determined that further evaluation of FT-4101 dose escalations for the study indication was not appropriate.

Results Point of Contact

• Title: Clinical Reporting Office (2834)
• Organization: FORMA Therapeutics, Inc.

clinicaltrials@novonordisk.com

(+1) 866-867-7178

Study Officials

• Clinical Transparency (dept. 2834), MD

  Novo Nordisk A/S

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2019
• First Posted: July 2, 2019
• Study Start: May 17, 2019
• Primary Completion: January 20, 2020
• Study Completion: January 20, 2020
• Last Updated: October 20, 2025
• Results First Posted: November 21, 2024

Record last verified: 2025-10

Locations

US (2)