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A Study of FT 4101 in Overweight/Obese Participants With NASH

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ClinicalTrials.gov Identifier: NCT04004325
Recruitment Status : Recruiting
First Posted : July 2, 2019
Last Update Posted : September 6, 2019
Sponsor:
Collaborator:
ProSciento, Inc.
Information provided by (Responsible Party):
Forma Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE June 10, 2019
First Posted Date  ICMJE July 2, 2019
Last Update Posted Date September 6, 2019
Actual Study Start Date  ICMJE May 17, 2019
Estimated Primary Completion Date January 10, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 4, 2019)
  • Incidence of adverse events [ Time Frame: Participants to be followed for duration of participation, which is approximately 20 weeks ]
  • Incidence of clinical lab abnormalities [ Time Frame: Participants to be followed for duration of participation, which is approximately 20 weeks ]
  • Change from baseline in vital signs (blood pressure [BP]: mmHg) [ Time Frame: Participants to be followed for duration of participation, which is approximately 20 weeks ]
  • Change from baseline in vital signs (heart rate [HR]: beats/min) [ Time Frame: Participants to be followed for duration of participation, which is approximately 20 weeks ]
  • Change from baseline in vital signs (respiratory rate [RR]: breaths/min) [ Time Frame: Participants to be followed for duration of participation, which is approximately 20 weeks ]
  • Change from baseline in vital signs (temperature [aural]: degrees Celsius) [ Time Frame: Participants to be followed for duration of participation, which is approximately 20 weeks ]
  • Change from baseline in 12-lead electrocardiogram (ECG) parameters (heart rate [HR]: beats/min) [ Time Frame: Participants to be followed for duration of participation, which is approximately 20 weeks ]
  • Change from baseline in 12-lead electrocardiogram (ECG) parameters (QT interval: milliseconds) [ Time Frame: Participants to be followed for duration of participation, which is approximately 20 weeks ]
  • Change from baseline in 12-lead electrocardiogram (ECG) parameters (PR interval: milliseconds) [ Time Frame: Participants to be followed for duration of participation, which is approximately 20 weeks ]
  • Change from baseline in 12-lead electrocardiogram (ECG) parameters (QRS interval: milliseconds) [ Time Frame: Participants to be followed for duration of participation, which is approximately 20 weeks ]
  • Change from baseline in 12-lead electrocardiogram (ECG) parameters (RR interval: milliseconds) [ Time Frame: Participants to be followed for duration of participation, which is approximately 20 weeks ]
  • Change from baseline in 12-lead electrocardiogram (ECG) parameters (QTcF interval: milliseconds) [ Time Frame: Participants to be followed for duration of participation, which is approximately 20 weeks ]
  • Reduction (absolute and relative) of % liver fat on MRI-PDFF [ Time Frame: Assessed at 12 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 27, 2019)
  • Incidence of adverse events [ Time Frame: Participants to be followed for duration of participation, which is approximately 20 weeks ]
  • Incidence of clinical lab abnormalities [ Time Frame: Participants to be followed for duration of participation, which is approximately 20 weeks ]
  • Change from baseline in vital signs (blood pressure [BP]: mmHg) [ Time Frame: Participants to be followed for duration of participation, which is approximately 20 weeks ]
  • Change from baseline in vital signs (heart rate [HR]: beats/min) [ Time Frame: Participants to be followed for duration of participation, which is approximately 20 weeks ]
  • Change from baseline in vital signs (respiratory rate [RR]: breaths/min) [ Time Frame: Participants to be followed for duration of participation, which is approximately 20 weeks ]
  • Change from baseline in vital signs (temperature [aural]: degrees Celsius) [ Time Frame: Participants to be followed for duration of participation, which is approximately 20 weeks ]
  • Reduction (absolute and relative) of % liver fat on MRI-PDFF [ Time Frame: Assessed at 12 weeks ]
Change History Complete list of historical versions of study NCT04004325 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2019)
  • Reduction (absolute and relative) of % liver fat on MRI-PDFF [ Time Frame: Assessed for up to approximately 20 weeks ]
  • Proportion of patients experiencing a relative reduction of 30% or greater of liver fat as assessed by MRI-PDFF [ Time Frame: Assessed for up to approximately 20 weeks ]
  • Assess the PD effect of FT-4101 on circulation biomarkers of liver inflammation after administration of multiple doses by assessment of the reduction of the following liver biochemistry markers: ALT, AST, γGT, Alkaline phosphatase, Total bilirubin [ Time Frame: Participants to be followed for duration of participation, which is approximately 20 weeks ]
  • Maximum concentration (Cmax) [ Time Frame: Blood samples for PK analysis collected at up to 9 study visits over the course of approximately 20 weeks ]
  • Time to maximum concentration (Tmax) [ Time Frame: Blood samples for PK analysis collected at up to 9 study visits over the course of approximately 20 weeks ]
  • Area under the concentration-time curve for a dosing interval (AUCtau) [ Time Frame: Blood samples for PK analysis collected at up to 9 study visits over the course of approximately 20 weeks ]
  • Trough plasma concentrations (Ctrough) at steady state [ Time Frame: Blood samples for PK analysis collected at up to 9 study visits over the course of approximately 20 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 27, 2019)
  • Assess the PD effect of FT-4101 on the inhibition of fasting hepatic de novo lipogenesis (DNL) after administration of multiple doses by using a 2-week deuterated water labeling protocol [ Time Frame: Blood samples for PD analysis collected at up to 11 study visits over the course of approximately 20 weeks ]
  • Total sebum production [ Time Frame: Skin surface sebum level measured using Sebumeter at up to 10 study visits over the course of approximately 20 weeks ]
  • Concentration of sebum lipids [ Time Frame: Sebum lipids measured using Sebutape at up to 5 study visits over the course of approximately 20 weeks ]
  • Assess the PD effect of FT-4101 after administration of multiple doses by assessment of circulating biomarkers of liver injury and fibrosis - Enhanced liver fibrosis (ELF) score [ Time Frame: Blood samples for PD analysis collected at up to 4 study visits over the course of approximately 20 weeks ]
  • Assess the PD effect of FT-4101 after administration of multiple doses by assessment of circulating biomarkers of liver injury and fibrosis - Cytokeratin-18 fragments [ Time Frame: Blood samples for PD analysis collected at up to 4 study visits over the course of approximately 20 weeks ]
  • Assess the PD effect of FT-4101 after administration of multiple doses by assessment of circulating biomarkers of liver injury and fibrosis - FibroSure® [ Time Frame: Blood samples for PD analysis collected at up to 4 study visits over the course of approximately 20 weeks ]
  • Assess the PD effect of FT-4101 after administration of multiple doses by assessment of circulating biomarkers of liver injury and fibrosis - PRO-C3 [ Time Frame: Blood samples for PD analysis collected at up to 4 study visits over the course of approximately 20 weeks ]
  • Assess the PD effect of FT-4101 after administration of multiple doses by assessment of circulating metabolic parameters - Fasting Lipids [ Time Frame: Blood samples for PD analysis collected at up to 4 study visits over the course of approximately 20 weeks ]
  • Assess the PD effect of FT-4101 after administration of multiple doses by assessment of circulating metabolic parameters - Gycemic parameters [ Time Frame: Blood samples for PD analysis collected at up to 4 study visits over the course of approximately 20 weeks ]
  • Assess the PD effect of FT-4101 after administration of multiple doses by assessment of circulating metabolic parameters - Adiponectin [ Time Frame: Blood samples for PD analysis collected at up to 4 study visits over the course of approximately 20 weeks ]
  • Assess the PD effect of FT-4101 after administration of multiple doses by assessment of circulating metabolic parameters - FGF-21 [ Time Frame: Blood samples for PD analysis collected at up to 4 study visits over the course of approximately 20 weeks ]
  • Assess the PD effect of FT-4101 after administration of multiple doses by assessment of circulating metabolic parameters - Malonyl carnitine [ Time Frame: Blood samples for PD analysis collected at up to 4 study visits over the course of approximately 20 weeks ]
  • Steatosis (CAP) determined by FibroScan® [ Time Frame: Assessed at 12 weeks ]
  • Liver stiffness (LSM) determined by FibroScan® [ Time Frame: Assessed at 12 weeks ]
  • Imaging parameters (Liver Volume [L], Liver Fat Volume Index [L]) assessed by MRI-PDFF [ Time Frame: Imaging parameters assessed at up to 3 study visits over the course of approximately 20 weeks ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A Study of FT 4101 in Overweight/Obese Participants With NASH
Official Title  ICMJE A Phase 1/2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability and Efficacy of FT-4101 in Overweight/Obese Subjects With NASH
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Nonalcoholic Steatohepatitis (NASH)
  • Overweight or Obesity
Intervention  ICMJE
  • Drug: FT-4101
    FT-4101 will be supplied as active capsules and will be administered per the protocol defined frequency and dose level.
  • Drug: FT-4101 placebo
    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.
  • Other: Deuterated Water
    Deuterated water will be provided as individual ready-to-use, single dose bottles each containing 50 mL of deuterated water (70%).
Study Arms  ICMJE
  • Experimental: Cohort A
    Interventions:
    • Drug: FT-4101
    • Drug: FT-4101 placebo
    • Other: Deuterated Water
  • Experimental: Cohort B
    Interventions:
    • Drug: FT-4101
    • Drug: FT-4101 placebo
    • Other: Deuterated Water
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 27, 2019)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2020
Estimated Primary Completion Date January 10, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Meets all of the following criteria:

    1. CAP ≥ 300 dB/m by FibroScan® OR Liver biopsy within 24 months, consistent with NASH with stage 2-3 fibrosis
    2. 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:

    1. 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
    2. HbA1c < 9% (one retest is permitted with the result of the last test being conclusive)
    3. Fasting plasma glucose (FPG) < 240 mg/dL (<13.3 mmol/L)
  • Waist circumference ≤ 57 inches
  • Female subjects must be non-pregnant and non-lactating

Key Exclusion Criteria:

  • 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)
  • History of major depression, anxiety, suicidal behavior or attempts, or other unstable psychiatric disorders (within 2 years of screening), requiring medical treatment
  • Uncontrolled hypertension
  • Any device or other contraindication with the MRI examination
  • Ingestion of deuterated water within the previous 6 months
  • Positive test for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus type 1 (HIV-1) or type 2 (HIV-2) antibody
  • Participation in any other clinical interventional study receiving active treatment within the previous 30 days or 5 half-lives, whichever is longer
  • Unable to abstain from smoking during confinement periods
  • History of illicit drug abuse
  • Clinically under the effect of marijuana at screening
  • Unwillingness to abstain from grapefruit (grapefruit containing food and beverages), star fruit (carambola), pomegranate, Seville orange and other food components that may interact with CYP3A4 from check-in throughout the entire course of the study
  • Donation or loss of > 500 mL of blood or blood product within 56 days of dosing
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Christine Dyer-Ward 857-209-2873 cdyerward@formatherapeutics.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04004325
Other Study ID Numbers  ICMJE 4101-MET-201
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Forma Therapeutics, Inc.
Study Sponsor  ICMJE Forma Therapeutics, Inc.
Collaborators  ICMJE ProSciento, Inc.
Investigators  ICMJE
Study Director: Patrick Kelly, MD Forma Therapeutics
PRS Account Forma Therapeutics, Inc.
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP