Clinical trial • Phase III • Rare Disease
RECOMBINANT HUMAN ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 FUSED TO THE FC FRAGMENT OF IGG1 for Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) deficiency
Phase III trial of RECOMBINANT HUMAN ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 FUSED TO THE FC FRAGMENT OF IGG1 for Ectonucleotide pyrophosphatas…
Overview
- Trial Therapeutic Area
- Rare Disease
- Trial Disease
- Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) deficiency
- Trial Stage
- Phase III
- Drug Modality
- Peptide/protein/enzyme
- Paediatric Trial
- Yes
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 03-11-2023
- First CTIS Authorization Date
- 06-03-2024
Trial design
Randomised, open-label, active control: conventional therapy provided locally by each site (active control); no specific drug name, dose, or standardized schedule specified in part i, adaptive Phase III trial in France, Spain.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Active control: Conventional therapy provided locally by each site (active control); no specific drug name, dose, or standardized schedule specified in Part I
- Adaptive
- True, dose-escalation and extension elements are planned: initial Randomized Treatment Period (RTP) with INZ-701 2.4 mg/kg once weekly vs active control; Low Dose Open-Label Extension where all participants receive INZ-701 2.4 mg/kg QW while primary analysis is pending; if Dose Escalation Criteria are met, participants may enter a Randomized Extension Period and then High-Dose Open-Label Extension with higher frequency dosing (e.g. INZ-701 1.8 mg/kg twice weekly).
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 26
- Trial Duration For Participant
- 364
Eligibility
Recruits 26 paediatric patients.
- Pregnancy Exclusion
- 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
- Vulnerable Population
- Participants are children (males and females ≥1 year and <13 years). Caregiver’s written informed consent is required prior to any research procedures and study participant assent is required in accordance with local regulations. Age-specific assent and consent materials are provided (e.g. assent forms for ages 4-6 and 7-12, parent/legal guardian ICF). eConsent (ClinOne) and telephone pre-ICF consent procedures are available; materials and ICF/assent documents are provided in multiple languages (English, Spanish, French, Italian, Portuguese, Polish, German/DE-AT among others) per submitted documentation.
Inclusion criteria
- {"criterion_text":"- 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)"}
- {"criterion_text":"- 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"}
- {"criterion_text":"- WOCBP and partners of fertile males who are WOCBP must be using or must agree to use a highly effective form of contraception (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)"}
- {"criterion_text":"- In the opinion of the Investigator, able to complete all aspects of the study"}
- {"criterion_text":"- Study participant’s assent in accordance with local regulations"}
- {"criterion_text":"- 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"}
- {"criterion_text":"- Males and females ≥1 year and <13 years of age at Study Day 1"}
- {"criterion_text":"- Open growth plates of the distal femur and proximal tibia in both legs"}
- {"criterion_text":"- Plasma PPi concentration of <1400 nM at Screening"}
- {"criterion_text":"- 25(OH)D levels of ≥12 ng/mL at Screening"}
- {"criterion_text":"- Radiographic evidence of skeletal abnormalities based on an RSS ≥2"}
- {"criterion_text":"- 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"}
Exclusion criteria
- {"criterion_text":"- 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"}
- {"criterion_text":"- 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"}
- {"criterion_text":"- 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"}
- {"criterion_text":"- Planned orthopedic surgery or other procedures that may confound the interpretation of study results during the 52-week RTP"}
- {"criterion_text":"- Known intolerance to INZ-701 or any of its excipients"}
- {"criterion_text":"- A positive COVID-19 test within 5 days prior to Randomization, only if required as per local regulations or institutional policy"}
- {"criterion_text":"- Previous treatment with INZ-701"}
- {"criterion_text":"- 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"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Change from Baseline in plasma PPi concentration through Week 52","definition_or_measurement_approach":"Plasma PPi concentration measured and change from baseline assessed through Week 52 (to determine if INZ-701 increases PPi levels)"}
- {"endpoint_text":"- RGI-C global score through Week 52","definition_or_measurement_approach":"Change from baseline in Radiographic Global Impression of Change (RGI-C) global score through Week 52 (to assess improvement in skeletal abnormalities)"}
Secondary endpoints
- {"endpoint_text":"- Change from Baseline in RSS total score through Week 52","definition_or_measurement_approach":"Change from baseline in Rickets Severity Score (RSS) total score through Week 52"}
- {"endpoint_text":"- Change from Baseline in growth Z-score (height/body length and weight) through Week 52","definition_or_measurement_approach":"Change from baseline in growth Z-scores for height/body length and weight through Week 52"}
- {"endpoint_text":"- Measurement of INZ-701 serum concentration and enzyme activity","definition_or_measurement_approach":"Pharmacokinetic measurement of INZ-701 serum concentration and assessment of ENPP1 enzyme activity"}
- {"endpoint_text":"- Please refer to the protocol for Tertiary and Safety endpoints","definition_or_measurement_approach":"Details of tertiary and safety endpoints are provided in the study protocol"}
Recruitment
- Registry Or Advocacy Recruitment
- True, Rare Disease Research Partners Limited
- Digital Remote Recruitment
- True, includes eConsent (ClinOne), electronic patient diary (Umotif), remote pre-ICF telephone consent and other digital patient-facing materials
- Planned Sample Size
- 26
- Recruitment Window Months
- 34
- Consent Approach
- Caregiver/parental written informed consent required prior to any research procedures; study participant assent required in accordance with local regulations. eConsent is implemented (ClinOne) with patient-facing submission packets and reference manuals. Age-specific assent and information sheets are provided (assent 4-6 years; assent 7-12 years) and parent/legal guardian ICFs are provided. Documents and consent materials are available in multiple languages (English, Spanish, French, Italian, Portuguese, Polish, German/DE-AT, etc.) as per submitted documentation.
Methods
- Family webinars (recruitment material titled 'Family Webinar' available in multiple languages)
- Informational booklets for families (available in multiple languages)
- Scout Travel Considerations Questionnaire (documents to assess travel needs and support for participants/families)
- Scout pre-ICF telephone data consent (telephone contact for pre-ICF screening and data consent)
- E-consent via ClinOne (electronic consent platform and patient reference manuals)
- Patient-facing materials including Subject ID cards and Notices regarding travel insurance
Geography
- Total Number Of Sites
- 2
- Total Number Of Participants
- 8
France
- Earliest CTIS Part Ii Submission Date
- 14-12-2023
- Latest Decision Or Authorization Date
- 30-03-2026
- Processing Time Days
- 837
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Pediatric Endocrinology and Diabetes for Children
- Principal Investigator Name
- Agnès LINGLART
- Principal Investigator Email
- agnes.linglart@aphp.fr
- Contact Person Name
- Agnès LINGLART
- Contact Person Email
- agnes.linglart@aphp.fr
- Number Of Participants
- 1
Spain
- Earliest CTIS Part Ii Submission Date
- 26-02-2024
- Latest Decision Or Authorization Date
- 08-04-2025
- Processing Time Days
- 407
- Number Of Sites
- 1
- Number Of Participants
- 7
Sites
- Site Name
- Sant Joan De Deu Barcelona Hospital
- Department Name
- Pediatric
- Principal Investigator Name
- Pedro Arango Sancho
- Principal Investigator Email
- pedro.arango@sjd.es
- Contact Person Name
- Pedro Arango Sancho
- Contact Person Email
- pedro.arango@sjd.es
- Number Of Participants
- 7
Sponsor
Primary sponsor
- Full Name
- Inozyme Pharma Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Worldwide Clinical Trials
- Responsibilities
- Site agreement; operational support; sponsorDuties include codes 1,12,15,5 (as listed)
- Name
- Bioclinica Inc.
- Responsibilities
- X-Ray central collection and reader
- Name
- Clinone Inc.
- Responsibilities
- E-consent implementation
- Name
- Medrio Inc.
- Responsibilities
- Electronic data capture / data management (sponsorDuties codes 3 and 7 listed)
- Name
- Red Nucleus Solutions LLC
- Responsibilities
- Video support on scales
Third parties
- {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"Depot/Clinical Supplies","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Alliance Pharma Inc.","duties_or_roles":"Analyzing samples for PPi, PK, ENPP1 Activity, Immunogenicity","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Biomarin Pharmaceutical Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Biomarkers - CTX (for Type 1 Collagen Antigen)","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Umotif Limited","duties_or_roles":"Electronic Diary","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Rare Disease Research Partners Limited","duties_or_roles":"Assist study participants and their families","organisation_type":"Patient organisation/association"}
- {"country":"United Kingdom","full_name":"Mde Services Group Limited","duties_or_roles":"Nursing services; Patient facing materials and reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"Serum Chemistry and Hematology, Urinalysis, Biomarkers (PINP & FGF23)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"X-Ray central collection and reader","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Croatia","full_name":"Worldwide Clinical Trials","duties_or_roles":"Site agreement; multiple operational responsibilities (codes 1,12,15,5 as listed)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Clinone Inc.","duties_or_roles":"E-consent","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Red Nucleus Solutions LLC","duties_or_roles":"Video support on scales","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Medrio Inc.","duties_or_roles":"Responsibilities indicated by sponsor duty codes (3,7) as listed","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- INZ-701
- Active Substance
- RECOMBINANT HUMAN ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 FUSED TO THE FC FRAGMENT OF IGG1
- Modality
- Peptide/protein/enzyme
- Routes Of Administration
- SUBCUTANEOUS USE
- Route
- Subcutaneous
- Authorisation Status
- Unapproved (investigational)
- Orphan Designation
- Yes
- Starting Dose
- 2.4 mg/kg once weekly
- Dose Levels
- 2.4 mg/kg once weekly; 1.8 mg/kg twice weekly (in Randomized Extension/High-Dose extension periods)
- Frequency
- Once weekly (RTP); Twice weekly (REP/high-dose extension)
- Maximum Dose
- 2.4 mg/kg (product data field 'maxTotalDoseAmount' = 2.4 mg/kg)
- Dose Escalation Increase
- Initial: 2.4 mg/kg once weekly; Following (if dose escalation criteria met): 1.8 mg/kg twice weekly
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