Not yet recruitingRare disease

Safety and Tolerability Study of Subcutaneous Pegtibatinase in Adults and Children with Classical Homocystinuria (Phase 1/2)

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What is this trial about?

A plain-language summary of the goals, design and what participants do

In this research, a rare metabolic disorder called Classical Homocystinuria is being studied. The condition causes the body to build up certain amino acids, leading to problems with the eyes, bones, and brain. The investigational medicine being tested is a protein called pegtibatinase, also known by the code TVT-058, which is given by a subcutaneous injection (an injection placed under the skin) to help break down the excess substances.

The purpose of the study is to determine how safe and well‑tolerated the medication is for people with this disorder. Participants will be randomly assigned to receive either the active drug or a placebo in a double-blind manner (meaning neither the participants nor the study staff know which treatment is being given) and will be followed for several weeks with regular check‑ups, blood tests, and heart rhythm recordings. Researchers will also look at whether the body creates an immune response to the drug, known as immunogenicity (the tendency to trigger antibodies).

During the study, volunteers will attend clinic visits where they will receive the assigned injection, have blood drawn to measure drug levels and metabolic markers, and undergo simple safety assessments such as blood pressure checks and an electrocardiogram (a test that records the heart’s electrical activity). Any side effects or changes in laboratory results will be recorded, and the overall health and quality‑of‑life information will be collected throughout the treatment period.

The research process

The trial runs in 8 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Enrollment and consent
After joining the study you will sign an informed consent form that explains the purpose of the trial and the procedures involved.
The study team will record your personal information and medical history.
Step 2
Baseline assessments
You will undergo a series of tests before receiving any medication, including blood and urine samples, a 12‑lead electrocardiogram (ecg) to check heart rhythm, and measurements of vital signs such as blood pressure and heart rate.
Questionnaires about your quality of life and cognitive function may also be completed.
Step 3
Randomization (double‑blind) or open‑label assignment
Participants in cohorts 1‑6 are placed in a double‑blind group, meaning neither you nor the investigators know whether the injection contains the active drug or a placebo.
Participants in cohort 7 (pediatric) receive the drug in an open‑label manner, meaning both you and the investigators know the injection contains the study medication.
Step 4
First subcutaneous injection of <b>pegtibatinase</b>
The study medication is given as a subcutaneous injection, which is an injection under the skin.
The exact dose and volume are determined by the study protocol and will be prepared by the study staff.
The injection is administered in a clinical setting by a trained professional.
Step 5
Repeated dosing schedule
You will receive additional injections of pegtibatinase at regular intervals defined by the study (for example weekly or every other week).
Each visit includes monitoring for side effects, measurement of vital signs, and collection of blood samples to assess drug levels and metabolic markers.
Step 6
Ongoing safety monitoring
At each visit you will be asked about any adverse events (aes), which are any new or worsening symptoms.
Laboratory tests (blood chemistry, hematology, urinalysis) and an ecg will be repeated to detect any changes.
The study may also test for antibodies against pegtibatinase or polyethylene glycol (peg) to evaluate immune response.
Step 7
Efficacy assessments
Periodically you will undergo specific assessments to evaluate the effect of the treatment, such as eye examinations, bone density scans, cognitive tests, and quality‑of‑life questionnaires.
Blood samples will be measured for homocysteine, methionine, and other metabolites related to your condition.
Step 8
End of treatment and final evaluation
After the predefined treatment period ends, you will have a final set of safety and efficacy assessments similar to the baseline visit.
The study medication will be stopped, and you will receive guidance on any further follow‑up care.

Who can join the trial?

6 criteria

Confirmed diagnosis of classical homocystinuria (HCU) by genetic testing that shows mutations in the CBS gene
Blood test showing plasma total homocysteine (tHcy) level of at least 50 µM (micromoles per liter) at screening, with a previous record of a level of at least 80 µM
Age between 12 and 65 years at the screening visit for the adult groups (participants must be at least 18 years old to join Cohort 1)
For the pediatric group (Cohort 7), age must be at least 5 years and younger than 12 years when signing the consent
Willing and able to follow all study procedures, as judged by the investigator
For the open‑label extension, you must have already participated in one of the double‑blind cohorts (Cohorts 1‑6) and continue to meet all the criteria listed above

Who cannot join the trial?

11 criteria

You have already received pegtibatinase, taken part in a study that gave pegtibatinase (or pegtarviliase for children), or have been exposed to these drugs before.
You have used or plan to use any injectable medicines that contain PEG (polyethylene glycol) – other than pegtibatinase or COVID‑19 vaccines – within three months before screening or during the study (this includes shots like Depo‑Provera).
You have had a serious allergic reaction to a product that contains PEG, such as trouble breathing, stomach upset, fever, very low blood pressure, swelling under the skin (angioedema), or a severe allergy called anaphylaxis.
You are allergic (have a hypersensitivity) to any part of pegtibatinase.
You have had an organ transplant or are taking medicines that suppress your immune system (immunosuppressive therapy).
You have another major health problem (for example, heart, lung, liver, kidney, blood, digestive, hormone, immune, skin, nerve, cancer, or mental health disease) that could make the study unsafe or difficult for you, other than complications from homocystinuria.
You develop intolerance to the study drug while taking it in the open‑label extension phase.
You have been diagnosed with Marfan syndrome, MTHFR deficiency, or a disorder of vitamin B12 (cobalamin) metabolism.
You weigh less than 15 kg (about 33 lb), which is below the weight requirement for the pediatric group.
You have had a severe immune reaction with systemic symptoms (such as the breathing, stomach, fever, blood pressure, swelling, or anaphylaxis signs listed above) to a PEG-containing product.
You have a history of organ transplantation or severe chronic immunosuppressive therapy within the last six months before screening (specific to the pediatric group).

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Hopital Necker Enfants Malades
Paris, France

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Investigated drugs

Pegtibatinase is an experimental enzyme that is being tested to help people with a rare condition called homocystinuria, which is caused by a deficiency in an enzyme needed to process certain amino acids. In this trial, the drug is given as a subcutaneous injection (under the skin) to see if it is safe and well‑tolerated, how it behaves in the body, and whether it can improve clinical outcomes. The study looks at both adult and pediatric participants, giving the medication in a double‑blind phase for adults and an open‑label phase for children, to gather information on safety, how the body reacts to the drug, and any potential benefits for managing the disease.

What is already known about the treatment

Pegtibatinase - Pegtibatinase is supplied as a lyophilized powder that is reconstituted and given by subcutaneous injection. It is an investigational orphan drug currently being studied in phase 1/2 trials for safety and effectiveness in people with classical homocystinuria, a rare metabolic disorder caused by lack of the enzyme cystathionine‑beta‑synthase. The drug works by providing a pegylated form of the missing enzyme, which helps break down excess homocysteine in the blood and lowers its harmful levels. It is classified as an enzyme‑replacement biologic.

Investigated diseases

Classical homocystinuria - Classical homocystinuria is an inherited disorder that impairs the body’s ability to break down the amino acid homocysteine. The condition leads to a buildup of homocysteine and related substances in the blood and urine. Over time, this accumulation can affect the eyes, bones, and the nervous system, causing changes such as lens displacement, reduced bone density, and learning difficulties. Symptoms often appear in early childhood and may become more noticeable as the child grows. The disease progresses gradually, with metabolic abnormalities persisting throughout life if not managed.