Pegtibatinase as a Treatment for Patients with Classical Homocystinuria (HCU) (also known as the COMPOSE Study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Travere Therapeutics Switzerland GmbH, Travere Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Decision date (initial)

2026-07-07

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Travere Therapeutics, Inc. 3611 Valley Centre Drive, Suite 300 San Diego, CA 92130 USA

External identifiers

EU CT number

2023-509074-31-00

ClinicalTrials.gov

NCT03406611

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Pharmacokinetic, Pharmacodynamic

Double-Blind Treatment Period (Cohorts 1-6):
Primary objective: To determine the dose-related safety and tolerability of pegtibatinase administered subcutaneously (SC) in participants with HCU

Pediatric Open-label Treatment Period (Cohort 7):
To determine the dose-related safety, tolerability, and immunogenicity of pegtibatinase administered SC in pediatric participants with classical homocystinuria.

Secondary objectives 2

1. Double-Blind Treatment Period (Cohorts 1-6): To determine the exposure parameters of pegtibatinase following single and repeat SC administration at specified timepoints; To determine the PD effects on Met cycle metabolites (eg, plasma tHcy, Met, and cystathionine [Cth]) plasma concentrations following SC administration of pegtibatinase; To determine the effects of SC administration of pegtibatinase on clinical outcomes, including ocular, skeletal, neurologic/psychiatric, and cognitive assessments
2. Pediatric Open-label Treatment Period (Cohort 7): To determine the PK parameters of pegtibatinase following single and repeat SC administration; To determine the PD effects on Met cycle metabolites (plasma tHcy, Met) levels following SC administration of pegtibatinase

Conditions and MedDRA coding

Classical Homocystinuria

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Requests for clinical trial data, including language stating its intended use, should be directed to [email protected]. If approved, the requested information will be provided to the requestor after signing a data access agreement. Requests can be made following completion of the study and full publication of the study data in a peer reviewed journal for up to 36 months following its publication. Travere reserves the right to decline or recommend modifications to a request if it does not comply with the data sharing policy or if it is determined that the request is made by a biased source.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Double-blind Treatment Period (Cohorts 1-6): 1. A diagnosis of HCU with the following: 1.1. Confirmation of genetic HCU by mutation analysis of CBS gene AND 1.2. Plasma tHcy ≥50 µM at Screening, confirmed by retest as appropriate AND documentation of previous plasma tHcy level ≥80 µM; 2. At the screening visit, ≥12 and ≤65 years of age (participants must be ≥18 years old to be eligible for Cohort 1); 3. Willing and able to comply, as assessed by the Investigator, with all study related procedures.
2. OLE Period (Cohorts 1-6): A participant must have participated in 1 of the double-blind treatment cohorts (1 through 6) and continue to meet the above main study criteria.
3. Pediatric Open-label Treatment Period (Cohort 7): 1. Participants must be ≥5 and <12 years of age, at the time of signing the informed consent/assent; 2. Participants must have a diagnosis of HCU based on clinical, biochemical, and/or molecular genetic testing; 3. Plasma tHcy ≥50 µM at Screening; 4. Willing and able to comply, as assessed by the Investigator, with all study-related procedures.

Exclusion criteria 3

1. Double-blind Treatment Period (Cohorts 1-6): 1. Previous exposure to pegtibatinase and/or previous participation in a clinical trial that included administration of pegtibatinase; 2. Use or planned use of any injectable drugs containing PEG (other than pegtibatinase or coronavirus disease 2019 [COVID-19] vaccines), including medroxyprogesterone (eg, Depo-Provera) injection, within 3 months prior to Screening and during study participation; 3. A prior reaction that included systemic symptoms (eg, abnormal respiratory or gastrointestinal signs or symptoms, fever, hypotension, angioedema, or anaphylaxis) to a PEG-containing product; 4. Known hypersensitivity to any components of pegtibatinase; 5. A history of organ transplantation or of chronic immunosuppressive therapy; 6. Concurrent disease or condition (eg, history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurological, oncologic, or psychiatric disease) that would interfere with study participation or safety (excluding complications of HCU).
2. OLE Period (Cohorts 1-6): 1. The participant developed an intolerance to the study drug.
3. Pediatric Open -label Treatment Period (Cohort 7): 1. Diagnosis of Marfan syndrome, methylenetetrahydrofolate reductase (MTHFR) deficiency, or disorder of cobalamin metabolism, based on clinical, biochemical, and/or molecular genetic testing. 2. Concurrent disease or condition (eg, history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurological, oncologic, or psychiatric disease) that would interfere with study participation or safety (excluding complications of HCU); 3. Body weight <15 kg; 4. Use or planned use of any injectable drugs containing PEG (other than pegtibatinase and PEG-containing vaccines), including medroxyprogesterone (eg, Depo-Provera) injection, within 3 months prior to Screening and during study participation; 5. Previous exposure to pegtibatinase and/or previous participation in a clinical trial that included administration of pegtibatinase or pegtarviliase. Participants may be consented to the ENSEMBLE study prior to COMPOSE study completion to ensure continuity of study drug between the 2 studies; 6. A prior severe immune reaction that included systemic symptoms (eg, abnormal respiratory or gastrointestinal signs or symptoms, fever, hypotension, angioedema, or anaphylaxis) to a PEG-containing product; 7. Known hypersensitivity to any components of pegtibatinase; 8. A history of organ transplantation or severe chronic immunosuppressive therapy during the last 6 months prior to Screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Double-Blind Treatment Period (Cohorts 1-6): Incidence of adverse events (AEs) by type, severity, and relationship to study drug; Changes from baseline in clinical laboratory findings (serum chemistries, hematology, urinalysis, and coagulation parameters); 12-lead electrocardiogram (ECG) parameters; Presence and levels of anti-pegtibatinase and anti-polyethylene glycol (PEG) antibodies
2. Pediatric Open-label Treatment Period (Cohort 7): Incidence of AEs; Changes from baseline in vital signs, clinical laboratory findings; 12-lead ECG parameters; Immunogenicity (Anti-pegtibatinase antibodies, Anti-PEG antibodies, Neutralizing antibodies); Proportion of participants requiring dietary protein rescue; Incidence of hypermethioninemia; Incidence of hypomethioninemia

Secondary endpoints 2

1. Double-Blind Treatment Period (Cohorts 1-6): Pegtibatinase levels following single and repeat administration at specified timepoints; Met cycle metabolites and Phe levels; Clinical efficacy endpoints (Ophthalmology, Bone densitometry, Cognitive assessments, Patient Reported Outcomes, Quality of life questionnaire)
2. Pediatric Open-label Treatment Period (Cohort 7): • Plasma concentrations of pegtibatinase, including maximum concentration (Cmax), and area under curve (AUC), and additional PK parameters, as appropriate following single and repeat administration • The change from baseline in plasma tHcy levels • The change from baseline in plasma Met levels

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Travere Therapeutics Switzerland GmbH

Sponsor organisation

Travere Therapeutics Switzerland GmbH

Address

Zurcherstrasse 6

City

Rapperswil Sg

Postcode

8640

Country

Switzerland

Scientific contact point

Organisation

Travere Therapeutics Switzerland GmbH

Contact name

Travere Call Center

Public contact point

Organisation

Travere Therapeutics Switzerland GmbH

Contact name

Travere Call Center

Travere Therapeutics Inc.

Sponsor organisation

Travere Therapeutics Inc.

Address

3611 Valley Centre Drive Suite 300

City

San Diego

Postcode

92130-3331

Country

United States

Scientific contact point

Organisation

Travere Therapeutics Inc.

Contact name

Travere Call Center

Public contact point

Organisation

Travere Therapeutics Inc.

Contact name

Travere Call Center

Third parties 11

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications