Clinical trial NCT04004325: A Study of FT 4101 in Overweight/Obese Participants With Non-alcoholic Steatohepatitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Nonalcoholic Steatohepatitis (NASH)
Overweight or Obesity
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
Collaborators: name: ProSciento, Inc.
First posted: 2019-07-02
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration up to 20 weeks
measure: Number of Participants With Clinically Significant Changes in Laboratory Values
timeFrame: Up to 20 weeks
measure: Number of Participants With Clinically Significant Changes in Physical Examination
timeFrame: Up to 20 weeks
measure: Change From Baseline in Vital Signs: Blood Pressure (BP)
timeFrame: Baseline, Day 92
measure: Change From Baseline in Vital Signs: Heart Rate (HR)
timeFrame: Baseline, Day 92
measure: Change From Baseline in Vital Signs: Respiratory Rate
timeFrame: Baseline, Day 92
measure: Change From Baseline in Vital Signs: Temperature
timeFrame: Baseline, Day 92
measure: Change From Baseline in 12-lead Electrocardiogram (ECG) Parameters: ECG Mean Heart Rate
timeFrame: Baseline, Day 92
measure: Change From Baseline in 12-lead ECG Parameters: QT Interval
timeFrame: Baseline, Day 92
measure: Change From Baseline in 12-lead ECG Parameters: PR Interval
timeFrame: Baseline, Day 92
measure: Change From Baseline in 12-lead ECG Parameters: QRS Interval
timeFrame: Baseline, Day 92
measure: Change From Baseline in 12-lead ECG Parameters: RR Interval
timeFrame: Baseline, Day 92
measure: Change From Baseline in 12-lead ECG Parameters: QTc (Corrected) Using the Fridericia Correction (QTcF) Interval
timeFrame: Baseline, Day 92
measure: Percent Change From Baseline in Liver Fat on Magnetic Resonance Imaging- Proton Density Fat Fraction (MRI-PDFF)
timeFrame: At week 12
measure: Change From Baseline in Liver Fat on Magnetic Resonance Imaging- Proton Density Fat Fraction (MRI-PDFF)
timeFrame: At week 12
Secondary outcomes:
measure: Change From Baseline in Liver Fat on MRI-PDFF
timeFrame: At week 6
measure: Percent Change From Baseline in Liver Fat on MRI-PDFF
timeFrame: At week 6
measure: Percentage of Participants Experiencing a Relative Reduction of 30% or Greater of Liver Fat as Assessed by MRI-PDFF
timeFrame: At week 12
measure: Change From Baseline in Alanine Aminotransferase (ALT)
timeFrame: Baseline, Day 92
measure: Change From Baseline in Aspartate Aminotransferase (AST)
timeFrame: Baseline, Day 92
measure: Change From Baseline in Gamma-glutamyl Transferase (γGT)
timeFrame: Baseline, Day 92
measure: Change From Baseline in Alkaline Phosphatase
timeFrame: Baseline, Day 92
measure: Change From Baseline in Total Bilirubin
timeFrame: Baseline, Day 92
measure: Maximum Plasma Concentration (Cmax) of FT-4101
timeFrame: Cycle 1 (Day 1), Cycle 4 (Day 14); each Cycle length = 21 days
measure: Area Under the Concentration-time Curve for a Dosing Interval (AUCtau) of FT-4101
timeFrame: Cycle 1 (Day 1), Cycle 4 (Day 14); each Cycle length = 21 days
measure: Data for This Endpoint Was Not Collected and Analysed.
timeFrame: Cycle 1 (Day 1), Cycle 4 (Day 14); each Cycle length = 21 days
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: ProSciento, Inc.
state: California
city: Montclair
country: United States
facility: Catalina Research Institute
state: California
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 2834), MD
role: STUDY_DIRECTOR
References: