Clinical Research Directory

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

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.

A Study to Investigate Efficacy and Safety of Pegtibatinase Compared With Placebo in Participants ≥12 to ≤65 Years of Age With Classical Homocystinuria (HCU) Due to Cystathionine Beta Synthase Deficiency Receiving Standard of Care Treatment

The purpose of this study is to measure efficacy and safety of pegtibatinase treatment compared with placebo in participants with classical HCU receiving standard of care. Study details include: * Total Study duration: up to 38 weeks * Screening: * Initial Screening duration: up to 4 weeks * Pre-treatment Diet Standardization Period duration: up to 6 weeks * Blinded Treatment Duration: 24 weeks * 2-week blinded dose titration period * 22-week blinded assessment period * Safety Follow-Up: 4 weeks after last dose (as applicable for those not enrolling in the long term extension study, ENSEMBLE)

Early Check: Expanded Screening in Newborns

Early Check provides voluntary screening of newborns for a selected panel of conditions. The study has three main objectives: 1) develop and implement an approach to identify affected infants, 2) address the impact on infants and families who screen positive, and 3) evaluate the Early Check program. The Early Check screening will lead to earlier identification of newborns with rare health conditions in addition to providing important data on the implementation of this model program. Early diagnosis may result in health and development benefits for the newborns. Infants who have newborn screening in North Carolina will be eligible to participate, equating to over 120,000 eligible infants a year. Over 95% of participants are expected to screen negative. Newborns who screen positive and their parents are invited to additional research activities and services. Parents can enroll eligible newborns on the Early Check electronic Research Portal. Screening tests are conducted on residual blood from existing newborn screening dried blood spots. Confirmatory testing is provided free-of-charge for infants who screen positive, and carrier testing is provided to mothers of infants with fragile X. Affected newborns have a physical and developmental evaluation. Their parents have genetic counseling and are invited to participate in surveys and interviews. Ongoing evaluation of the program includes additional parent interviews.

A Long-term Extension Study to Assess the Long-term Safety and Efficacy of Pegtibatinase Treatment in Participants ≥5 to ≤65 Years of Age With Classical Homocystinuria (HCU) (ENSEMBLE)

The goal of this long-term extension (LTE) study is to evaluate the safety and efficacy of pegtibatinase in patients with classical homocystinuria (HCU). Patients who are active in the Phase 1/2 COMPOSE study or those who complete the 24 weeks of blinded treatment in the Phase 3 HARMONY are eligible to participate. Participants will be in this clinical study for a minimum of 108 weeks including: * a treatment period of up to 104 weeks * a 4-week safety follow-up period

Proof of Concept Creatine Supplementation for Homocystinuria Study

Homocystinuria is a rare and inherited metabolic disorder, people with this condition don't have an enzyme needed to break down an amino acid called homocysteine. When the body can't break down the homocysteine made from another amino acid methionine, it becomes toxic to the heart, brain, and bones. We are constantly eating methionine, a building block of protein, so a common treatment is eating a low-protein diet with medical foods and vitamin pills. This can be hard to follow due to bad tastes and missing out on foods a person enjoys, especially in children. The goal of this study is to provide participants with a supplement containing creatine, another amino acid related to methionine and homocysteine, and learn if it lowers homocysteine production in healthy adult men. We would ultimately like to see if creatine supplements are a potential alternate treatment of Homocystinuria in this proof of concept study, before studying individuals with the condition. Researchers in this study want to know: * How does the bodies digestion of isotope methionine change in breath and urine when creatine is taken in healthy young adult men? * How do levels of homocysteine, methionine and related metabolites change in the blood when creatine is taken by healthy young adult men? Participants will: * Complete two (2), 8-hour study days on-site. * Eat a lower protein diet for one (1) week before the first study day, and eat a lower protein diet with creatine supplements for one (1) week before the second study day. * During both study days eat special hourly meals of controlled amino acids and nutrients, along with a methionine isotope. (An isotope is a stable labelled amino acid that is colourless, odorless, tasteless, and safe for consumption. In the lab we can detect this isotope in breath and urine samples collected during the study day). * Provide samples of breath, urine and blood. (Researchers will also take body measurements (height weight), and use non-invasive tests to measure body composition and energy needs).

Health Related Quality of Life (HrQoL) in Classical Homocystinuria (CBS Deficiency)

Patients, parents of young / handicapped patients, and experts will be interviewed to collect contents relevant for HrQoL in CBS deficiency. Based on these data, a questionnaire will be developed and tested for comprehensibility in patients and parents of young / handicapped patients. A final questionnaire version will be tested for psychometric criteria including validity and reliability.