INZ-701 for ENPP1 Deficiency

Recruiting at 15 trial locations

Overseen By Inozyme Clinical Trial Information

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Inozyme Pharma

Must not be taking: Corticosteroids, FGF23 inhibitors, Bisphosphonates

Disqualifiers: Clinically significant disease, Orthopedic surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

27 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing INZ-701, a treatment that replaces a missing enzyme, in children with a rare genetic disorder called ENPP1 Deficiency. The goal is to see if it is safe and effective. The treatment helps by providing the enzyme their bodies lack.

Will I have to stop taking my current medications?

You may need to stop taking certain medications. Specifically, you cannot take systemic corticosteroids (more than 5 mg of prednisone per day), anti-fibroblast growth factor 23, oral or IV bisphosphonates, calcitriol, or other active forms of vitamin D3 within 7 days before the study starts, and oral phosphate supplements within 36 hours before the study if you are in the INZ-701 group.

What makes the drug INZ-701 unique for treating ENPP1 Deficiency?

INZ-701 is unique because it is a recombinant protein (a lab-made protein) designed to replace the missing or defective enzyme in people with ENPP1 Deficiency, which is a rare condition with no standard treatments. This drug works by mimicking the natural enzyme's function, potentially addressing the root cause of the disease. ^{1 2 3 4 5}

Research Team

Kurt Gunter, MD

Principal Investigator

Inozyme Pharma, Inc.

Eligibility Criteria

This trial is for children with ENPP1 Deficiency, showing specific bone abnormalities and growth plate activity. They must be between 1-12 years old, not pregnant or breastfeeding, willing to use contraception if applicable, and have certain vitamin D levels. Those who've had recent surgery or used certain medications like systemic corticosteroids are excluded.

Inclusion Criteria

Your plasma PPi concentration is less than 1400 nM at the time of screening.

I am between 1 and 12 years old.

I am not pregnant or breastfeeding.

Exclusion Criteria

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

I am not taking high doses of steroids, anti-FGF23 drugs, or bisphosphonates.

I am not currently in another clinical study or haven't taken any investigational drugs recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

7 weeks

Randomized Treatment

Participants receive either INZ-701 or control treatment for 52 weeks

52 weeks

Weekly visits for subcutaneous injections

Open-label Extension

All participants may receive INZ-701 after the randomized treatment period

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person) for End of Study Safety assessment

Treatment Details

Interventions

• INZ-701

Trial Overview The ENERGY 3 Study tests the safety and effectiveness of INZ-701 compared to conventional therapy in treating skeletal issues caused by ENPP1 Deficiency in children. Participants will either receive INZ-701 or stick with standard treatments to see which works better.

Participant Groups

Group I: INZ-701 Experimental Treatment 1 Intervention

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 and the Open-label Extension Period.

Group II: Control Arm (Conventional Therapy) Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Inozyme Pharma

Lead Sponsor

Trials

10

Recruited

1,400+

Findings from Research

A novel homozygous variant in the INPP4A gene was identified in a girl who experienced severe neurodevelopmental issues, including postnatal microcephaly and myoclonic seizures, leading to her death at 27 months, highlighting the critical role of INPP4A in brain development.

The study demonstrated that different isoforms of INPP4A have distinct subcellular localizations and functions, suggesting that mutations can disrupt these roles and contribute to neurodevelopmental disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

INPP4A-related genetic and phenotypic spectrum and functional relevance of subcellular targeting of INPP4A isoforms. Hecher, L., Harms, FL., Lisfeld, J., et al.[2023]

A novel gene, Inpp4b, was identified as a key regulator of nerve conduction velocity, with specific sequence variants linked to differences in motor evoked potential latencies in mice.

An association was found between an INPP4B polymorphism and multiple sclerosis in human cohorts, suggesting its potential role in the disease's pathophysiology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nerve conduction velocity is regulated by the inositol polyphosphate-4-phosphatase II gene. Lemcke, S., Müller, S., Möller, S., et al.[2016]

Mutations in the INPP4A gene, which encodes a phosphoinositide phosphatase, lead to different neurological diseases, with two specific mouse models showing distinct cerebellar and striatal degeneration phenotypes.

The study found that the severity of neurological symptoms in these mice correlates with the levels of INPP4A protein expression and its phosphatase activity, suggesting that understanding these variations could aid in developing targeted therapies for related human conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attenuated cerebellar phenotypes in Inpp4a truncation mutants with preserved phosphatase activity. Tran, DM., Yoshioka, N., Bizen, N., et al.[2023]

Two unrelated fetuses with nonimmune fetal hydrops were found to have likely pathogenic variants in the ITPR1 gene, identified through trio exome sequencing.

This study highlights a previously unreported severe fetal condition linked to ITPR1 missense variants, expanding the understanding of genetic conditions associated with this gene.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two unrelated fetuses with ITPR1 missense variants and fetal hydrops. Harris, S., Putra, M., Gilmore, KL., et al.[2023]

This study reports the first Korean case of a neurodevelopmental disorder caused by a novel de novo missense mutation in the PPP2R1A gene, highlighting the genetic basis of such disorders.

The 12-month-old patient exhibited severe symptoms including developmental delay, epilepsy, and brain abnormalities, which expands the understanding of the clinical features associated with PPP2R1A-related neurodevelopmental disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PPP2R1A-Related Neurodevelopmental Disorder: The First Korean Case with a Novel Variant of PPP2R1A and Literature Review. Lee, J., Yoo, J., Lee, S., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

INPP4A-related genetic and phenotypic spectrum and functional relevance of subcellular targeting of INPP4A isoforms. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Nerve conduction velocity is regulated by the inositol polyphosphate-4-phosphatase II gene. [2016]

3. England pubmed.ncbi.nlm.nih.gov

Attenuated cerebellar phenotypes in Inpp4a truncation mutants with preserved phosphatase activity. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Two unrelated fetuses with ITPR1 missense variants and fetal hydrops. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

PPP2R1A-Related Neurodevelopmental Disorder: The First Korean Case with a Novel Variant of PPP2R1A and Literature Review. [2023]