Ketohexokinase Inhibition in NAFLD

NCT05463575 | Completed Phase 2

• 1 other identifier: NL80131.068.22 / METC 22-006
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Fructose is a big contributor to the development of non-alcoholic fatty liver disease (NAFLD). Inhibiting ketohexokinase (KHK), the enzyme catalyzing the first committed step in fructose metabolism, is thought to reduced intrahepatic lipid (IHL) content. Pharmacological inhibition of KHK resulted in a decrease in IHL content in NAFLD patients, but additional health effects are still unknown. In this study the investigators aim to look at additional health effects following KHK inhibition (KHKi).

Conditions

NAFLD

Outcome Measures

Primary Outcomes (1)

• Hepatic insulin sensitivity

  insulin-mediated suppression of endogenous glucose production (EGP) in µmol/kg/min measured during the 2- step hyperinsulinemic-euglycemic clamp

  42 days

Secondary Outcomes (10)

• Intrahepatic lipid content

  41 days

• Liver lipid content composition

  41 days

• Subcutaneous adipose tissue

  41 days

• Visceral adipose tissue

  41 days

• Insulin-mediated suppression of free fatty acids

  42 days

Other Outcomes (5)

• Liver phosphomonoester levels

  41 days

• Peripheral insulin sensitivity

  42 days

• Metabolic flexibility

  42 days

Study Arms (2)

PF-06835919

EXPERIMENTAL

KHKi

Drug: Ketohexokinase inhibition

Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

Ketohexokinase inhibition DRUG

participants will be asked to take 300 mg of the KHKi in tablet form daily for 6 weeks in either period 1 or 2.

PF-06835919

Placebo OTHER

participants will be asked to take 300 mg of the placebo in tablet form daily for 6 weeks in either period 1 or period 2.

Placebo

Eligibility Criteria

• Age: 45 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are able to provide signed and dated written informed consent prior to any study specific procedures
• Men and (postmenopausal) woman
• Aged ≥ 45 and ≤ 70 years
• Body mass index (BMI) 27 - 35 kg/m2
• Hepatic steatosis (i.e. IHL ≥ 5.56%)
• Stable dietary habits (no weight loss or gain \> 3 kg in the past 3 months)

You may not qualify if:

• Type 2 diabetes
• Patients with congestive heart failure and and/or severe renal and or liver insufficiency
• Uncontrolled hypertension
• Any contra-indication for MRI scanning
• Alcohol consumption of \>3 servings per day for man and \>2 servings per day for woman
• Smoking
• Unstable body weight (weight gain or loss \> 3kg in the last 3 months)
• Engagement in structured exercise activities \> 2 hours a week
• Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the investigator which would possibly hamper our study results
• Use of drugs that inhibit organic anion transporting polypeptide (OATP) transporters (e.g. rifampicin, gemfibrozil, cyclosporine, erythromycin and clarithromycin)
• Subjects who do not want to be informed about unexpected medical findings

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Pfizer: collaborator

Study Sites (1)

Maastricht University Medical centre

Maastricht, Limburg, 6202AZ, Netherlands

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2022
• First Posted: July 19, 2022
• Study Start: October 1, 2022
• Primary Completion: November 24, 2023
• Study Completion: November 24, 2023
• Last Updated: January 24, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)