Ketohexokinase Inhibition in Hereditary Fructose Intolerance

NCT06089265 | Completed Phase 2

• 1 other identifier: NL83631.068.23 / METC23-006
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Hereditary fructose intolerance (HFI) is a rare inborn error of metabolism. Patients with HFI develop acute abdominal pain, nausea, vomiting, hypoglycemia and proximal tubular dysfunction upon consumption of a fructose containing food product. In rare cases, (prolonged) fructose consumption can even lead to liver and kidney failure. Patients with HFI are therefore treated with a lifelong fructose-restricted diet. Animal studies have shown that the clinical manifestations of HFI are abrogated upon inhibition of ketohexokinase (KHK), the enzyme that catalyses the first step in fructose metabolism. Recently, PF-06835919, a KHK inhibitor (KHKi), was developed as a new treatment for non-alcoholic fatty liver disease. The compound was well tolerated in several phase II clinical trials. It is hypothesized that PF-06835919 is also effective in patients with HFI.

Conditions

HFI

Outcome Measures

Primary Outcomes (8)

• Intestinal Fructose tolerance,

  a visual analog scale from 1-10 for abdominal pain will be used. Additional every 5 minutes the participant will be asked if he/she is nauseous, and more, less or similar nauseous as 5 minutes before.

  9 days

• Intestinal Fructose tolerance,

  Every 5 minutes the participant will be asked if he/she is nauseous, and more, less or similar nauseous as 5 minutes before.

  9 days

• Renal Fructose tolerance

  Urinary pH

  9 days

• Renal Fructose tolerance

  Glucose content, mmol/L

  9 days

• Renal Fructose tolerance

  Phosphate content mmol/L

  9 days

• Renal Fructose tolerance

  Amino acid content mmol/L

  9 days

• Hepatic fructose tolerance

  Serum glucose levels, mmol/L

  9 days

• Hepatic fructose tolerance

  Serum phosphate levels, mmol/L

  9 days

Secondary Outcomes (3)

• Intrahepatic lipid content

  9 days

• Blood pressure

  9 days

• Glycosylated transferrin

  9 days

Study Arms (2)

HFI patients

EXPERIMENTAL

HFI participants will receive PF-06835919 for 9 days. Dosage; once daily 300 mg PF-06835919 in the form of 3 tablets, oral.

Drug: PF-06801591

Healthy controls

NO INTERVENTION

Healthy controls will receive no intervention, but a single fructose tolerance test.

Interventions

PF-06801591 DRUG

Active ketohexokinase inhibitor

Also known as: KHKi

HFI patients

Eligibility Criteria

• Age: 18 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
• Use of effective contraception (only applicable to premenopausal women; a pregnancy test will be performed in these women at baseline)
• Aged ≥ 18 years

You may not qualify if:

• Diabetes mellitus
• Pregnancy
• Patients with congestive heart failure and/or severe renal and or liver insufficiency
• Uncontrolled hypertension
• 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 B1 (OATPB1) transporters (e.g. rifampicin, gemfibrozil, ciclosporine, erythromcyin and clarithromycin)\*
• Treatment with irinotecan\* Any contra-indications for MRI scanning\*
• 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

Study Officials

• Patrick Schrauwen, PhD

  Maastricht University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: all HFI participants will get the medication, no placebo will be used. Controls will get no medication or placebo.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: open label, pilot study

Study Record Dates

• First Submitted: May 15, 2023
• First Posted: October 18, 2023
• Study Start: June 15, 2023
• Primary Completion: November 30, 2023
• Study Completion: November 30, 2023
• Last Updated: January 24, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)