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.
Age
Cohort 7 (currently enrolling): ≥5 to <12 years of age.
Completed Cohorts 1-6: ≥12 to 65 years of age.
Diagnosis of classical homocystinuria (HCU)
Diagnosis of Marfan syndrome, methylenetetrahydrofolate reductase (MTHFR) deficiency, or a disorder of cobalamin metabolism.
History of a major thrombotic event within the previous 6 months.
Body weight <15 kg.
Previous treatment with pegtibatinase or pegtarviliase)
Parallel
Pegtibatinase
DrugPegtibatinase sterile solution for subcutaneous injection
Placebo
DrugNormal saline for subcutaneous injection
Incidence of AEs
Incidence of AEs (by type, severity and relationship to study drug)
Anti-pegtibatinase antibodies
Presence and levels of anti-pegtibatinase antibodies in plasma as measured by antibody titers
Anti-PEG antibodies
Presence and levels of anti-PEG antibodies in plasma as measured by antibody titers
Incidence of hypermethioninemia (Cohort 7 only)
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.
Changes in pegtibatinase levels
Changes in pegtibatinase levels following single and repeat administration at specified timepoints
Changes in Met cycle metabolites levels - tHcy
Changes in total homocysteine levels in micromoles
Changes in Met cycle metabolites levels - total Cys (Cohorts 1-6 Only)
Changes in total cysteine levels in micromoles
Changes in Met cycle metabolites levels - Me (Cohorts 1-6 Only)
Changes in methionine levels in micromoles
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