The ENABLE Study: Safety and Efficacy Study of INZ-701 in Patients With ENPP1 Deficiency

NCT06739980 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: INZ701-108
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of Study INZ701-108 (ENABLE) is to assess the safety and efficacy of INZ-701 in patients 1 year of age and older with ENPP1 Deficiency who have not previously received INZ-701 and are not eligible for existing Inozyme-sponsored clinical studies that are still open to enrollment.

Conditions

Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency; Autosomal Recessive Hypophosphatemic Rickets; Generalized Arterial Calcification of Infancy 1

Keywords

Ectonucleotide Pyrophosphatase/Phosphodiesterase1 Deficiency; Hypopyrophosphatemia; ENPP1; Autosomal Recessive Hypophosphatemic Rickets Type 2; ARHR2; Generalized Arterial Calcification of Infancy; GACI

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) concentration through Week 52

  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)

Secondary Outcomes (21)

• Change from Baseline in skeletal abnormalities as measured by the Radiographic Global Impression of Change (RGI-C) global score through Week 104 for patients 1 to <13 years

  52 weeks (Baseline through Week 52)

• Change from Baseline in Rickets Severity Score (RSS) total score through Week 104 (measured on all long bones with open growth plates in the knee or wrist) for patients 1 to <13 years

  104 weeks (Baseline through Week 104)

• Change from Baseline in arterial calcification score based on low dose computed tomography (CT) through Week 104 for patients 1 to <18 years

  104 weeks (Baseline through Week 104)

• Change over time in serum biomarkers: Fibroblast growth factor 23 for patients >1 year

  104 weeks (Baseline through Week 104)

• Change over time in serum biomarkers: Procollagen type 1 N-terminal propeptide for patients >1 year

  104 weeks (Baseline through Week 104)

Other Outcomes (2)

• Number of Treatment Adverse Events (TEAEs) through Week 104

  104 weeks (Baseline through Week 104)

• Incidence of Anti-Drug Antibodies (ADA) through Week 104

  104 weeks (Baseline through Week 104)

Study Arms (1)

INZ-701

EXPERIMENTAL

INZ-701 will be administered by SC injection on a once-weekly basis as follows: * Study participants from 1 year to \<18 years of age will receive a dose of 2.4 mg/kg * Study participants ≥18 years and: weighing \<50 kg or \>100 kg will receive a 1.8 mg/kg dose, OR weighing ≥50 and ≤100 kg will receive a 150 mg dose of INZ-701

Drug: INZ-701

Interventions

INZ-701 DRUG

Recombinant fusion protein that contains the extracellular domains of human ENPP1 coupled with an Fc fragment from an immunoglobulin gamma-1 (IgG1) antibody.

Also known as: (rhENPP1-Fc).

INZ-701

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written or electronic informed consent after the nature of the study has been explained, and prior to any research-related procedures, per International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP)
• Provide assent in accordance with local regulations, if \<18 years of age
• Male or female, ≥1 year of age
• A confirmed postnatal molecular genetic diagnosis of ENPP1 Deficiency with biallelic variants (ie, homozygous or compound heterozygous) performed using assays that meet CE-marked requirements, or from a College of American Pathologists/Clinical Laboratory Improvement Amendments (CAP/CLIA) certified laboratory, or regional equivalent
• Must have at least one of the following clinical signs and/or symptoms consistent with ENPP1 Deficiency:
• ≥1 atraumatic vertebral fracture
• ≥2 fractures as an adult (eg, long bones, digits, vertebrae)
• For participants \<55 years of age, low bone mineral density measured at any of the following sites: lumbar spine, radius, and hip (DXA Z-score less than -1.5)
• History of myocardial infarction, unstable angina, transient ischemic attack, or low cardiac output before the age of 40 years
• Renal vascular hypertension or other evidence for vascular insufficiency/stenosis
• History of rickets or bone deformity
• Diagnosis of ossification of the posterior longitudinal ligament
• Other clinical signs/symptoms, with approval by Inozyme
• Fasting plasma PPi concentration of \<1400 nM at Screening
• Serum level of 25-hydroxyvitamin D (25\[OH\]D) ≥12 ng/mL at Screening (Participants may be rescreened after receiving cholecalciferol treatment.)

You may not qualify if:

• In the opinion of the Investigator, presence of any clinically significant disease or laboratory abnormality not due to ENPP1 Deficiency that may confound interpretation of study results
• Eligible for another Inozyme sponsored study of INZ-701 treatment that is open for enrollment
• Receiving prohibited medications
• Unable or unwilling to discontinue calcitriol or other active forms of vitamin D3 (or analogs) within 7 days prior to Day 1 and/or oral phosphate supplements within 36 hours prior to Day 1
• Received previous treatment with INZ-701
• 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
• Pregnant, trying to become pregnant, or breastfeeding
• Male participants trying to father a child

Sponsors & Collaborators

• Inozyme Pharma: lead

MeSH Terms

Conditions

Hypophosphatemic Rickets, Autosomal Recessive, 1; Arterial calcification of infancy

Study Officials

• Inozyme Pharma, Inc.

  Inozyme Pharma, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2024
• First Posted: December 18, 2024
• Study Start: January 31, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2028
• Last Updated: May 1, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share