Pegtibatinase as a Treatment for Patients With Classical Homocystinuria (HCU) (Also Known as the COMPOSE Study)

Condition(s) studied

Investigational drug(s) / intervention(s)

Pegtibatinase: Pegtibatinase sterile solution for subcutaneous injection

Placebo: Normal saline for subcutaneous injection

Study summary

Researchers are looking for a better way to treat people who have classical homocystinuria (HCU), a rare condition that is passed down by parents (or "genetic condition"). It is caused by changes in the cystathionine beta-synthase (or "CBS") gene and prevents an enzyme from working correctly in the body. This enzyme breaks down a substance called homocysteine (from dietary methionine found in protein) and keeps both homocysteine and methionine at normal levels. When this enzyme is not working, homocysteine and methionine build up in the blood, which spreads into different tissues of the body and stops these body tissues from working normally.

People with HCU can experience problems with vision, bones, blood vessels, and cognitive function (the ability to think, learn, and remember). Treatments available for HCU, such as a low protein diet and betaine (Cystadane®), help reduce homocysteine levels. The diet is a low methionine diet and a methionine-free protein supplement (a product that provides extra protein to help meet daily protein needs). These treatments are either not sufficient or are hard to take for many patients.

Pegtibatinase was developed by scientists to be a version of the CBS enzyme that can be given to people with HCU. Researchers believe that giving pegtibatinase to people with HCU already getting medical treatment (or "standard of care") may reduce their homocysteine levels.

This study is split into 7 different groups getting different amounts of drug. The first 6 groups have already finished the study.

Group 7 plans to enroll participants from the US (virtual and in-person), France, and Qatar.

Eligibility

Primary outcome measure(s)

• Incidence of AEs — • Cohorts 1-6: Through double-blind study completion, approximately 10 months per patient • Cohort 7: First dose through End of Treatment (up to 32 weeks)
  Incidence of AEs (by type, severity and relationship to study drug)
• Anti-pegtibatinase antibodies — • Cohorts 1-6: Through double-blind study completion, approximately 10 months per patient • Cohort 7: First dose through End of Treatment (up to 32 weeks)
  Presence and levels of anti-pegtibatinase antibodies in plasma as measured by antibody titers
• Anti-PEG antibodies — • Cohorts 1-6: Through double-blind study completion, approximately 10 months per patient • Cohort 7: First dose through End of Treatment (up to 32 weeks)
  Presence and levels of anti-PEG antibodies in plasma as measured by antibody titers
• Incidence of hypermethioninemia (Cohort 7 only) — First dose through End of Treatment (up to Week 32)
  The number and percentage of participants who develop hypermethioninemia during treatment, based on plasma methionine concentrations exceeding the protocol-defined threshold. Participants meeting the protocol-defined threshold may undergo dietary management or study treatment modifications, as appropriate.
• Incidence of hypomethioninemia (Cohort 7 only) — First dose through End of Treatment (up to Week 32)
  The number and percentage of participants who develop hypomethioninemia during treatment, based on plasma methionine concentrations below the protocol-defined threshold. Participants meeting the protocol-defined threshold may receive dietary protein supplementation or study treatment modifications, as appropriate.
• The proportion of participants requiring dietary protein rescue (Cohort 7 only) — First dose through End of Treatment (up to Week 32)
  The proportion of participants who require initiation of dietary protein supplementation during study treatment to manage protocol-defined low plasma methionine concentrations.

Trial sites (12)

More Travere Therapeutics, Inc. trials in the USA

Other trials for the same condition