Ketohexokinase Inhibition in Hereditary Fructose Intolerance

• Status: Completed
• Trial end date: 2023-11-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Maastricht University Medical Center
• Collaborator: Pfizer

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• Exclusion criterion for HFI patients only.