El estudio ENERGY 3: Evaluación de la eficacia y seguridad de INZ-701 en niños con deficiencia de ENPP1
El estudio ENERGY 3: un estudio de fase 3 aleatorizado, controlado y abierto para evaluar la eficacia y seguridad de INZ-701 en niños con deficiencia de ectonucleótido pirofosfatasa/fosfodiesterasa 1 (ENPP1)
The primary purpose of Study INZ701-106 (The ENERGY 3 Study) is to assess the efficacy and safety of INZ-701 in children with ENPP1 Deficiency.
Descripción general del estudio
Estado
Estado
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Descripción detallada
INZ-701 is an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzyme replacement therapy (ERT) in development for the treatment of ENPP1 Deficiency, an ultra-rare genetic disorder with an incidence of 1 in 64,000 pregnancies.
Study INZ701-106 (The ENERGY 3 Study) is a multi-center, randomized in a 2:1 ratio, controlled, open-label Phase 3 study to evaluate the efficacy and safety of INZ-701 in children with ENPP1 Deficiency.
The study will consist of a Screening Period of up to 52 days (including a washout period of up to 7 days for prohibited medications post-Randomization) and a Randomized Treatment Period (INZ-701 or control) of 52 weeks, followed by an Open-label Extension Period during which all study participants may receive INZ-701, and an End of Study (EOS) Safety visit 30 days after the last dose of INZ-701.
Tipo de estudio
Tipo de estudio
Inscripción (Actual)
Inscripción
Fase
Fase
- Fase 3
Contactos y Ubicaciones
Ubicaciones de estudio
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Riyadh, Arabia Saudita, 12713
- King Faisal Specialist Hospital and Research Centre
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South Brisbane, Australia, 4101
- Queensland Children's Hospital
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Montreal, Canadá, H3T 1C5
- Centre Hospitalier Universitaire (CHU) Sainte-Justine
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Dubai, Emiratos Árabes Unidos, 30726
- Al Jalila Children's Specialty Hospital
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Illinois
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Chicago, Illinois, Estados Unidos, 60611
- Ann & Robert H. Lurie Children's Hospital
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19104
- The Children's Hospital of Philadelphia
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Texas
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Fort Worth, Texas, Estados Unidos, 76104
- Cook Children's Medical Center
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Le Kremlin-Bicêtre, Francia, 94270
- Hôpital Bicêtre, Service d'endocrinologie et diabète de l'enfant (Childhood Endocrinology and Diabetes Department)
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Manchester, Reino Unido, M13 9WL
- Royal Manchester Children's Hospital
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Istanbul, Turquía (Türkiye), 34764
- Umraniye Training and Research Hospital
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Sarıçam, Turquía (Türkiye), 01330
- Cukurova Universitesi Tip Fakultesi
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Criterios de participación
Criterio de elegibilidad
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria
Study participants must meet all of the following inclusion criteria:
- Caregiver's written informed consent after the nature of the study has been explained, and prior to any research-related procedures, per International Conference on Harmonisation (ICH) Good Clinical Practice (GCP)
- Study participant's assent in accordance with local regulations
- A confirmed postnatal molecular genetic diagnosis of ENPP1 Deficiency with biallelic mutations (ie, homozygous or compound heterozygous) performed by a College of American Pathologists/Clinical Laboratory Improvement Amendments (CAP/CLIA) certified laboratory or regional equivalent
- Males and females ≥1 year and <13 years of age at Study Day 1
- Open growth plates of the distal femur and proximal tibia in both legs
- Plasma PPi concentration of <1400 nM at Screening
- 25(OH)D levels of ≥12 ng/mL at Screening
- Radiographic evidence of skeletal abnormalities based on an RSS ≥2
- Women of childbearing potential (WOCBP, as defined in Clinical Trials Coordination Group [CTCG 2024]) must have a negative serum pregnancy test at Screening and must not be breastfeeding
- Males who are sexually active must agree to use condoms from the period following first dose of INZ-701 through 30 days after the last dose of INZ-701
- WOCBP and partners of fertile males who are WOCBP must be using or must agree to use a highly effective form of (as per CTCG) from at least 1 month before the first dose of INZ-701 through 30 days after the last dose of INZ-701 (greater than 5 half-lives of INZ-701)
- In the opinion of the Investigator, able to complete all aspects of the study
Exclusion Criteria
Study participants meeting any of the following exclusion criteria will not be eligible to participate in the study:
- In the opinion of the Investigator, has clinically significant disease or laboratory abnormality not associated with ENPP1 Deficiency that will preclude study participation and/or may confound the interpretation of study results
- If receiving any of the following prohibited medications as indicated in the protocol: systemic corticosteroids (>5 mg prednisone equivalent per day), anti-FGF23 and oral and/or IV bisphosphonates
- Unable or unwilling to discontinue calcitriol or other active forms of vitamin D3 (or analogs) within 7 days prior to Study Day 1 and/or oral phosphate supplements within 36 hours prior to Study Day 1 if randomized to the INZ-701 arm
- Planned orthopedic surgery or other procedures that may confound the interpretation of study results during the 52-week RTP
- Known intolerance to INZ-701 or any of its excipients
- A positive COVID-19 test within 5 days prior to Randomization, only if required as per local regulations or institutional policy
- Previous treatment with INZ-701
- Concurrent participation in another interventional clinical study and/or has received an investigational drug within 5 half-lives of the last dose or within 4 weeks prior to the first dose of INZ-701, whichever is longer, or use of an investigational device
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Número de brazos
Armas e Intervenciones
Grupo de participantes/brazoGrupo de participantes/brazo |
Intervención / TratamientoIntervención / Tratamiento |
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Experimental: INZ-701
Subjects randomized to the INZ-701 arm will be administered a 2.4 mg/kg once weekly dose by subcutaneous (SC) injection for the duration of the 52-week Randomized Treatment Period (RTP). RTP will be followed by a Low-dose Open-label Extension Period during which all study participants will receive INZ-701 at a dose of 2.4 mg/kg QW while the primary analysis is pending. If dose escalation criteria are met, all participants will transition to the Randomized Extension Period (REP) where participants who were originally randomized to INZ-701 during RTP will transition to a higher dose regimen of INZ-701 at 1.8 mg/kg twice weekly. Participants who were originally randomized to the active control arm during RTP will continue receiving INZ-701 at 2.4 mg/kg QW in the REP. |
Recombinant fusion protein that contains the extracellular domains of human ENPP1 coupled with an Fc fragment from an immunoglobulin gamma-1 (IgG1) antibody.
Otros nombres:
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Comparador activo: Control Arm (Conventional Therapy)
Subjects randomized to the control arm will continue taking their conventional therapy as clinically indicated by their treating physician for the duration of the 52-week Randomized Treatment Period. |
Conventional therapy is defined as oral phosphate supplements and calcitriol or other active forms of vitamin D3 (or analogs). No other agents for treatment of ENPP1 Deficiency are allowed in the control arm. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) concentration through Week 52
Periodo de tiempo: 52 weeks (Baseline through Week 52)
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For each subject, plasma PPi will be measured via a series of blood samples obtained throughout the study, comparing the subject's baseline value over time. |
52 weeks (Baseline through Week 52)
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Change from Baseline in skeletal abnormalities as measured by the Radiographic Global Impression of Change (RGI-C) global score through Week 52
Periodo de tiempo: 52 weeks (Baseline through Week 52)
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The RGI-C is an overall radiographic score which can be used to monitor response to a therapeutic intervention comparing scores from 2 time points. A determination of healing on a scale of 0 to +3 with 0 being no change or healing and +3 being complete healing; worsening is also measured on a scale of 0 to -3 with 0 being no change and -3 being severe worsening. |
52 weeks (Baseline through Week 52)
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Medidas de resultado secundarias
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Change from Baseline in rickets as measured by Rickets Severity Score (RSS) total score through Week 52
Periodo de tiempo: Baseline, Week 26, Week 52
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The RSS assesses rickets severity by utilizing a scoring system that uses a scale from 0 to 4 for the wrists and 0 to 6 for the knees, to generate a total score of 0 to 10, where 0 is normal and 10 is the worst score possible ie, most severe skeletal abnormalities observed radiographically. |
Baseline, Week 26, Week 52
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Change from Baseline in growth Z-score (height/body length and weight) through Week 52
Periodo de tiempo: Baseline, Day 29, Week 8, Week 13, Week 26, Week 39, Week 52
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A Z-score represents the degree to which that particular measurement for that individual differs from the reference value in the general population. (height/body length and weight) through Week 52 |
Baseline, Day 29, Week 8, Week 13, Week 26, Week 39, Week 52
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Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701
Periodo de tiempo: 52 weeks (Randomized Treatment Period)
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For each subject, variation of concentration of INZ-701 in the plasma will be measured via a series of blood samples obtained throughout the study, comparing the subject's baseline value over time. |
52 weeks (Randomized Treatment Period)
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Maximum Plasma Concentration (Cmax) of INZ-701
Periodo de tiempo: 52 weeks (Randomized Treatment Period)
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For each subject, the maximum concentration of INZ-701 in the plasma will be measured via a series of blood samples obtained throughout the study, comparing the subject's baseline value over time. |
52 weeks (Randomized Treatment Period)
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Change from Baseline in ENPP1 activity (µM/min) through week 52
Periodo de tiempo: 52 weeks (Randomized Treatment Period)
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For each subject, the activity of INZ-701 (µM/min) in the serum will be assessed through hydrolysis of a substrate to the enzyme, via a series of blood samples obtained throughout the study, comparing the subject's baseline value over time. |
52 weeks (Randomized Treatment Period)
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Colaboradores e Investigadores
Patrocinador
Patrocinador
Colaboradores
Colaboradores
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Inicio del estudio
Finalización primaria (Actual)
Finalización primaria
Finalización del estudio (Actual)
Finalización del estudio
Fechas de registro del estudio
Enviado por primera vez
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Publicado por primera vez
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización publicada
Última actualización enviada que cumplió con los criterios de control de calidad
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
Otros números de identificación del estudio
- INZ701-106
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
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