Recombinant human ectonucleotide pyrophosphatase/phosphodiesterase 1 fused to the Fc fragment of IgG1 for Ectonucleotide pyrophosphatase/phosphodiesterase 1 deficiency (ENPP1 deficiency)

Inclusion criteria

• {"criterion_text":"- Caregiver(s) written or electronic consent after the nature of the study has been explained, and prior to any research-related procedures, per International Council on Harmonisation (ICH) Good Clinical Practice (GCP)\n- A confirmed postnatal molecular genetic diagnosis of ENPP1 Deficiency with biallelic mutations (ie, homozygous or compound heterozygous) performed using assays that meet CE-marked requirements, or by a College of American Pathologists/Clinical Laboratory Improvement Amendments (CAP/CLIA) certified laboratory, or a regional equivalent\n- Clinical manifestations of GACI, which must include at least one of the following: ectopic calcification, heart failure, respiratory distress, edema, cyanosis, hypertension, and cardiomegaly. Heart failure is defined as a structural and/or functional abnormality that produces raised intracardiac pressures and/or inadequate cardiac output resulting in characteristic signs and symptoms including edema and respiratory distress. Cardiomegaly is defined as cardiothoracic ratio exceeding 0.5 by chest X-ray or increased left ventricular mass on echocardiography or cross-sectional imaging relative to normal based on Investigator judgment.\n- Males and females from birth to <1 year of age at Study Day 1\n- Plasma PPi concentration of <1400 nM: a. at study Screening if study participant has not participated in the EAP. b. at the documented baseline prior to treatment with INZ-701 in the EAP\n- Body weight ≥0.5 kg at the time of the first dose of INZ-701\n- Be able to complete all aspects of the study in the opinion of the Investigator\n- Caregiver(s) agree to provide access to their infant’s relevant medical records"}

Exclusion criteria

• {"criterion_text":"- In the opinion of the Investigator, presence of any clinically significant disease or laboratory abnormality not associated with ENPP1 Deficiency that will preclude study participation and/or may confound interpretation of study results\n- Care has been withdrawn or infant is receiving end of life or hospice care\n- Planned surgery that may confound the interpretation of study results during the 52-week Treatment Period in the opinion of the Investigator\n- Known intolerance to INZ-701 or any of its excipients\n- Previous treatment with INZ-701 unless prior treatment was part of the EAP, in which case they may participate upon Sponsor approval\n- Concurrent participation in another interventional clinical study and/or has received an investigational drug within 5 half-lives or within 4 weeks prior to the first dose of INZ-701, whichever is longer, or use of an investigational device"}

Primary endpoints

• {"endpoint_text":"- Change from Baseline in plasma PPi concentration through Week 52","definition_or_measurement_approach":"Change from baseline in plasma inorganic pyrophosphate (PPi) concentration measured through Week 52 (plasma PPi assays as specified in protocol)."}
• {"endpoint_text":"- Overall survival based on time from date of birth to event of all-cause mortality through Week 52","definition_or_measurement_approach":"Time-to-event measure: time from date of birth to all-cause mortality event, assessed through Week 52."}

Secondary endpoints

• {"endpoint_text":"- Change from Baseline in left ventricular ejection fraction via echocardiography through Week 52","definition_or_measurement_approach":"Change from baseline measured by echocardiography (LVEF) through Week 52."}
• {"endpoint_text":"- Incidence of heart failure","definition_or_measurement_approach":"Occurrence/incidence of heart failure events as defined in protocol during the assessment period."}
• {"endpoint_text":"- Change from Baseline in vascular calcification in the coronary arteries and aorta via CT scan through Week 52","definition_or_measurement_approach":"Change from baseline in vascular calcification assessed by CT imaging of coronary arteries and aorta through Week 52."}
• {"endpoint_text":"- Change from Baseline in growth Z-score (body length and weight) through Week 52","definition_or_measurement_approach":"Change from baseline in growth Z-scores for body length and weight through Week 52."}
• {"endpoint_text":"- Growth velocity","definition_or_measurement_approach":"Assessment of growth velocity (rate of change in growth measures) per protocol schedule."}
• {"endpoint_text":"- Number of days of mechanical ventilation","definition_or_measurement_approach":"Count of days on mechanical ventilation during the assessment period."}
• {"endpoint_text":"- Measurement of INZ-701 plasma concentration and ENPP1 activity","definition_or_measurement_approach":"Pharmacokinetic measurement of INZ-701 plasma concentration and measurement of ENPP1 enzymatic activity per protocol-specified assays."}

Methods

• Pre-ICF telephone pre-screening (Scout Clinical Pre-ICF Telephone Data Consent) targeting caregivers of potentially eligible infants (documents available with country-specific versions).
• Electronic consent (e-consent) for caregivers implemented (Clinone listed with e-consent responsibility).
• Patient-facing materials and travel reimbursement/travel management to support participation (Mde Services Group Limited responsibilities include patient facing materials, nursing services, reimbursement and patient travel management/support).
• Use of patient organisation support to assist participants and families (Rare Disease Research Partners Limited listed to assist study participants and their families).
• Use of remote/digital tools for participant data capture and diaries (Umotif electronic diary, Medrio for data capture) and country-specific ICF and recruitment documents.

France

Earliest CTIS Part Ii Submission Date

29-07-2024

Latest Decision Or Authorization Date

11-05-2026

Processing Time Days

651

Number Of Sites

1

Number Of Participants

2

Hungary

Earliest CTIS Part Ii Submission Date

30-07-2024

Latest Decision Or Authorization Date

15-05-2026

Processing Time Days

654

Number Of Sites

1

Number Of Participants

1

Italy

Earliest CTIS Part Ii Submission Date

04-07-2024

Latest Decision Or Authorization Date

11-05-2026

Processing Time Days

676

Number Of Sites

1

Number Of Participants

1

Spain

Earliest CTIS Part Ii Submission Date

30-08-2024

Latest Decision Or Authorization Date

17-09-2025

Processing Time Days

383

Number Of Sites

1

Number Of Participants

1

Sweden

Earliest CTIS Part Ii Submission Date

30-08-2024

Latest Decision Or Authorization Date

27-01-2025

Processing Time Days

150

Number Of Sites

1

Number Of Participants

1

Primary sponsor

Full Name

Inozyme Pharma Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Worldwide Clinical Trials d.o.o.

Responsibilities

Site agreements and operational/site responsibilities (as listed among sponsor third parties)

Name

Clinone Inc.

Responsibilities

e-consent

Name

Bioclinica Inc.

Responsibilities

Echo and CT collection

Name

Medrio Inc.

Third parties

• {"country":"United Kingdom","full_name":"Mde Services Group Limited","duties_or_roles":"patient facing materials, nursing services, reimbursement and patient travel management/support","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Voisin Consulting Life Sciences","duties_or_roles":"safety reporting, pharmacovigilance","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Serum Chemistry and Hematology, Urinalysis, Biomarkers (PINP & FGF23)","organisation_type":"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":"Croatia","full_name":"Worldwide Clinical Trials d.o.o.","duties_or_roles":"Site agreement (and other operational/site responsibilities)","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":"Medrio Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Umotif Limited","duties_or_roles":"electronic diary","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Echo and CT collection","organisation_type":"Laboratory/Research/Testing facility"}
• {"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 States","full_name":"Alliance Pharma Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"Depot/Clinical Supplies","organisation_type":"Pharmaceutical company"}