Clinical trial • Phase III • Endocrinology | Rare Disease

PEGTIBATINASE for Classical homocystinuria (cystathionine beta-synthase deficiency)

Phase III trial of PEGTIBATINASE for Classical homocystinuria (cystathionine beta-synthase deficiency).

Overview

Trial Therapeutic Area
Endocrinology | Rare Disease
Trial Disease
Classical homocystinuria (cystathionine beta-synthase deficiency)
Trial Stage
Phase III
Drug Modality
Peptide/protein/enzyme
Paediatric Trial
Yes
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
30-12-2025
First CTIS Authorization Date
27-04-2026

Trial design

Randomised, placebo: 0.9 % sodium chloride saline solution (nacl); dose/schedule not specified-controlled Phase III trial across 19 sites in Belgium, France, Ireland and others.

Randomised
Yes
Comparator
Placebo: 0.9 % sodium chloride saline solution (NaCL); dose/schedule not specified
Biomarker Stratified
True, baseline plasma total homocysteine (tHcy) strata: ≥50 to <80 µM; ≥80 µM (enrolment quotas ~25% and ~75% respectively)
Target Sample Size
48
Trial Duration For Participant
168

Eligibility

Recruits 48 paediatric patients.

Vulnerable Population
Vulnerable populations selected. The trial includes minors (participants aged 12–17) and provisions for incapacitated adults. Subject information, assent and consent materials are provided for Minors Assent (12–17), Parents and Legal Representatives ICF, and Incapacitated/Incabable Adults Assent; country-specific ICF/assent documents are available (multiple languages). Parental/legal representative consent is used for minors with assent from minors where appropriate; separate materials for parents/guardians and genetic consent documents are provided.

Inclusion criteria

  • {"criterion_text":"- Individuals eligible to be enrolled into this study must have a diagnosis of HCU based on clinical, biochemical, and/or molecular genetic testing. Approximately 25% of participants may be enrolled with a Screening plasma tHcy ≥50 to <80 µM, and the remaining majority (approximately 75%) of participants will be enrolled with a Screening plasma tHcy ≥80 µM.\n- Individuals must also be ≥12 to ≤65 years of age at Screening, and be willing to maintain a stable diet with consistent levels of DIPI, and HCU-related therapies such as betaine, pyridoxine, and medical food (eg, metabolic formula), if applicable, as part of pre-study treatment"}

Exclusion criteria

  • {"criterion_text":"- Diagnosis of Marfan syndrome, methylenetetrahydrofolate reductase (MTHFR) deficiency, or disorders of cobalamin metabolism; body weight ≥160 kg (measured from screening through the PND)\n- Any prior exposure to pegtibatinase or pegtarviliase\n- Use or planned use of any injectable drug containing PEG (other than pegtibatinase or PEG containing vaccines)\n- History of a severe immune reaction to a PEG containing product; organ transplant; or intensive chronic immunosuppressive treatment within the 6 months prior to screening"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The change from baseline averaged over Week -3, Week -1, and Day 1 pre-dose in plasma tHcy levels averaged over Weeks 6 through 12 (6, 8, 10, and 12) in participants receiving standard of care and treated with pegtibatinase as compared to placebo","definition_or_measurement_approach":"Change from baseline in plasma total homocysteine (tHcy). Baseline is averaged over Week -3, Week -1 and Day 1 pre-dose; outcome is average of measurements at Weeks 6, 8, 10 and 12. Comparison is pegtibatinase + standard of care versus placebo + standard of care."}

Secondary endpoints

  • {"endpoint_text":"- The change from baseline in plasma tHcy levels averaged post Week 12 (Weeks 16, 20, and 24) in participants receiving standard of care and treated with pegtibatinase as compared to placebo","definition_or_measurement_approach":"Change from baseline in plasma tHcy averaged at Weeks 16, 20 and 24 comparing pegtibatinase versus placebo."}
  • {"endpoint_text":"- The change from baseline in plasma Met levels averaged over Weeks 6 through 12 in participants receiving standard of care and treated with pegtibatinase as compared to placebo","definition_or_measurement_approach":"Change from baseline in plasma methionine (Met) averaged at Weeks 6, 8, 10 and 12 comparing pegtibatinase versus placebo."}
  • {"endpoint_text":"- The change from baseline in plasma Met levels averaged post Week 12 in participants receiving standard of care and treated with pegtibatinase as compared to placebo","definition_or_measurement_approach":"Change from baseline in plasma methionine (Met) averaged at post-Week 12 visits comparing pegtibatinase versus placebo."}
  • {"endpoint_text":"- The proportion of participants achieving tHcy <100 µM averaged over Weeks 6 through 12, among participants with tHcy ≥100 µM at baseline","definition_or_measurement_approach":"Proportion of baseline tHcy ≥100 µM participants who have tHcy <100 µM when averaged across Weeks 6–12."}
  • {"endpoint_text":"- The proportion of participants achieving tHcy <100 µM averaged post Week 12 among participants with tHcy ≥100 µM at baseline","definition_or_measurement_approach":"Proportion of baseline tHcy ≥100 µM participants who have tHcy <100 µM when averaged at post-Week 12 visits."}
  • {"endpoint_text":"- The proportion of participants with tHcy <50 µM averaged over Weeks 6 through 12","definition_or_measurement_approach":"Proportion of participants with plasma tHcy <50 µM averaged across Weeks 6–12."}
  • {"endpoint_text":"- The proportion of participants with tHcy <50 µM averaged post Week 12","definition_or_measurement_approach":"Proportion of participants with plasma tHcy <50 µM averaged at post-Week 12 visits."}
  • {"endpoint_text":"- The proportion of participants achieving tHcy reduction ≥35% from baseline averaged over Weeks 6 through 12, and averaged post Week 12","definition_or_measurement_approach":"Proportion achieving ≥35% reduction in plasma tHcy from baseline averaged across Weeks 6–12 and averaged at post-Week 12 visits."}
  • {"endpoint_text":"- The proportion of participants achieving tHcy <100 µM and a ≥35% reduction from baseline averaged over Weeks 6 through 12, and averaged post Week 12 among participants with tHcy ≥100 µM at baseline","definition_or_measurement_approach":"Composite responder endpoint among baseline tHcy ≥100 µM participants: both tHcy <100 µM and ≥35% reduction achieved averaged over Weeks 6–12 and post-Week 12."}
  • {"endpoint_text":"- The proportion of participants with tHcy ≤15 µM averaged over Weeks 6 through 12, and averaged post Week 12","definition_or_measurement_approach":"Proportion of participants with plasma tHcy ≤15 µM averaged across Weeks 6–12 and at post-Week 12 visits."}

Recruitment

Registry Or Advocacy Recruitment
True, HCU Connection
Digital Remote Recruitment
True, recruitment via trial websites and online patient-facing materials (website pages, online patient flyers) and contact by email (medinfo@travere.com) are specified
Planned Sample Size
48
Recruitment Window Months
14
Consent Approach
Informed consent obtained using subject information sheets and ICFs; adults provide written informed consent. For minors (participants aged 12–17) a Minors Assent form is provided plus Parental/Legal Representative ICF for parent/guardian consent. Incapacitated/incapable adults have specific assent materials. Country-specific ICF and assent documents are provided in multiple languages (English, French, Dutch, Italian, Portuguese, Spanish, Polish as per uploaded documents).

Methods

  • Patient flyer (country-specific patient flyers listed) — target: patients with classical homocystinuria / caregivers
  • Website (trial website pages listed per country) — target: patients/caregivers and clinicians
  • HCU Connection (website/registry referenced in recruitment material) — target: HCU patient community/registry
  • Travere Call Center (medinfo@travere.com) — central contact channel for inquiries

Geography

Total Number Of Sites
19
Total Number Of Participants
22

Belgium

Earliest CTIS Part Ii Submission Date
01-04-2026
Latest Decision Or Authorization Date
29-04-2026
Processing Time Days
28
Number Of Sites
2
Number Of Participants
3

Sites

Site Name
Cliniques Universitaires Saint-Luc
Department Name
Department of Pediatry
Contact Person Name
Marie-Cecile Nassogne
Contact Person Email
PCIC@aintluc.uclouvain.be
Number Of Participants
3
Site Name
Universitair Ziekenhuis Antwerpen
Department Name
ORG-100009995
Contact Person Name
Sandra Kingma
Contact Person Email
sandra.kingma@uza.be

France

Earliest CTIS Part Ii Submission Date
23-02-2026
Latest Decision Or Authorization Date
27-04-2026
Processing Time Days
63
Number Of Sites
3
Number Of Participants
4

Sites

Site Name
CHRU De Nancy
Department Name
Service de Médecine Infantile
Contact Person Name
François Feillet
Contact Person Email
f.feillet@chru-nancy.fr
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
Médecine interne
Contact Person Name
François Maillot
Contact Person Email
recherche.miic@chu-tours.fr
Site Name
Hopital Necker Enfants Malades
Department Name
Service Maladies Métaboliques Pédiatriques
Contact Person Name
Manuel Schiff
Contact Person Email
manuel.schiff@aphp.fr

Ireland

Earliest CTIS Part Ii Submission Date
27-03-2026
Latest Decision Or Authorization Date
01-05-2026
Processing Time Days
35
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
Children's Health Ireland
Department Name
The National Centre for Inherited Metabolic Disorders (NCIMD)
Contact Person Name
Ahmad Monavari

Italy

Earliest CTIS Part Ii Submission Date
20-04-2026
Latest Decision Or Authorization Date
28-04-2026
Processing Time Days
8
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
Azienda Universitaria Ospedaliera Consorziale Policlinico Bari
Department Name
Department of Pediatrics, Unit of Metabolic and Genetic Diseases
Contact Person Name
Albina Tummolo

Portugal

Earliest CTIS Part Ii Submission Date
13-03-2026
Latest Decision Or Authorization Date
30-04-2026
Processing Time Days
48
Number Of Sites
2
Number Of Participants
2

Sites

Site Name
Unidade Local De Saude De Coimbra E.P.E.
Department Name
Internal Medicine
Contact Person Name
Sónia Moreira
Contact Person Email
10357@ulscoimbra.minsaude.pt
Site Name
Unidade Local De Saude De Santa Maria E.P.E.
Department Name
Internal Medicine
Contact Person Name
Anabela Oliveira
Contact Person Email
cic@ulssm.min-saude.pt

Spain

Earliest CTIS Part Ii Submission Date
24-04-2026
Latest Decision Or Authorization Date
04-05-2026
Processing Time Days
10
Number Of Sites
6
Number Of Participants
6

Sites

Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Endocrinology
Contact Person Name
Eva Venegas Moreno
Contact Person Email
evam.venegas.sspa@juntadeandal
Site Name
Complexo Hospitalario Universitario De Santiago
Department Name
Internal Medicine and Paediatrics Departments
Contact Person Name
Alvaro Hermida Ameijeiras
Site Name
Hospital Universitario 12 De Octubre
Department Name
Internal Medicine
Contact Person Name
Montserrat Morales
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Unidad de Enfermedades Metabólicas. Servicio de Pediatria
Contact Person Name
Amaya Belanguer
Site Name
Hospital Sant Joan De Deu Barcelona
Department Name
Pediatric Neurology
Contact Person Name
Angels García Carzola
Contact Person Email
frecerca.startup@sjd.es
Site Name
Hospital Universitario (other listed site)

Poland

Earliest CTIS Part Ii Submission Date
01-04-2026
Latest Decision Or Authorization Date
30-04-2026
Processing Time Days
29
Number Of Sites
2
Number Of Participants
2

Sites

Site Name
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki W Krakowie
Department Name
Oddział Diabetologii, Chorób Wewnętrznych i Metabolicznych
Contact Person Name
Lukasz Pawlinski
Contact Person Email
Pawlinski@su.krakow.pl
Site Name
Instytut Pomnik Centrum Zdrowia Dziecka
Department Name
Klinika Pediatrii, Pawlinski@su.krakow.pl
Contact Person Name
Dariusz Rokicki
Contact Person Email
rokicki@ipczd.pl

Germany

Earliest CTIS Part Ii Submission Date
22-04-2026
Latest Decision Or Authorization Date
07-05-2026
Processing Time Days
15
Number Of Sites
2
Number Of Participants
3

Sites

Site Name
Universitaetsklinikum Leipzig AöR
Department Name
Department of Endocrinology, Nephrology and Rheumatology
Contact Person Name
Haiko Schloegel
Site Name
Universitaetsklinikum Muenster AöR
Department Name
Department of Congenital Metabolic Disorders
Contact Person Name
Thorsten Marquardt
Contact Person Email
Anja.wolf@ukmunester.de

Sponsor

Primary sponsor

Full Name
Travere Therapeutics Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
PPD International Holdings LLC
Responsibilities
code 4
Name
CTI Clinical Trial and Consulting Services Europe GmbH
Responsibilities
codes 1,12,2,5,6
Name
Precision for Medicine (HU) Kft.
Responsibilities
code 10
Name
4g Clinical LLC
Responsibilities
code 3
Name
Emvenio Clinical Research LLC
Responsibilities
Home HealthCare

Third parties

  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code 7","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Emvenio Clinical Research LLC","duties_or_roles":"Home HealthCare","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United Kingdom","full_name":"Cambridge Cognition Limited","duties_or_roles":"ePROs","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"PPD International Holdings LLC","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
  • {"country":"Finland","full_name":"Blueprint Genetics Oy","duties_or_roles":"code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"code 3","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Hungary","full_name":"Precision for Medicine (HU) Kft.","duties_or_roles":"code 10","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"CTI Clinical Trial and Consulting Services Europe GmbH","duties_or_roles":"codes 1,12,2,5,6","organisation_type":"Pharmaceutical company"}
  • {"country":"India","full_name":"Qinecsa Solutions India Private Limited","duties_or_roles":"code 8","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"Participant travel and expenses reimbursement","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Central ECG and Ophthalmic Image reader","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Pegtibatinase
Active Substance
PEGTIBATINASE
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS INJECTION
Route
SUBCUTANEOUS INJECTION
Authorisation Status
MIA: DE_BW_01_MIA_2024_0081
Orphan Designation
Yes
Maximum Dose
2.5 mg/kg
Investigational Product Name
0.9 % sodium chloride saline solution (NaCL)
Modality
Other
Combination Treatment
Yes

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