INZ-701 for ENPP1 Deficiency

Not currently recruiting at 18 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness and safety of a new treatment called INZ-701 for children with ENPP1 Deficiency, a rare genetic disorder affecting bone and mineral health. Participants are divided into two groups: one receives the experimental treatment (INZ-701), while the other continues their current therapy. Children diagnosed with ENPP1 Deficiency through genetic testing and who have experienced related bone issues may be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that INZ-701 is likely to be safe for humans?

Research has shown that INZ-701 is generally safe and well-tolerated in people with ENPP1 Deficiency. In several studies, patients taking INZ-701 experienced no serious side effects. This treatment aims to improve the body's mineral use, crucial for maintaining healthy bones.

Some patients in these studies reported mild side effects, but these were not severe enough to discontinue the treatment. Overall, the evidence suggests that INZ-701 is a promising option for those with ENPP1 Deficiency, aiming to enhance health without causing major issues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard care for ENPP1 deficiency, which often relies on conventional therapies to manage symptoms, INZ-701 takes a novel approach by targeting the underlying cause of the condition. INZ-701 works by replacing a missing enzyme, which could help restore normal function in affected pathways. Researchers are excited about INZ-701 because it offers a targeted treatment that could potentially improve outcomes significantly for patients by addressing the root of the problem rather than just alleviating symptoms.

What evidence suggests that INZ-701 might be an effective treatment for ENPP1 Deficiency?

Studies have shown that INZ-701, which participants in this trial may receive, shows promise in treating ENPP1 Deficiency, a rare genetic disorder. It positively affects bone and mineral health, crucial for patients with this condition. Research over a 48-week period indicates significant improvements in measurable disease indicators and health outcomes for adults with ENPP1 Deficiency treated with INZ-701. This treatment replaces a missing or deficient enzyme in the body. Initial findings suggest it may effectively address some of the main problems caused by ENPP1 Deficiency. ^{1 3 4 6 7}

Who Is on the Research Team?

Kurt Gunter, MD

Principal Investigator

Inozyme Pharma, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06739980

Safety and Efficacy Study of INZ-701 in Patients With ... 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.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04686175?intr=INZ-701&rank=5

Evaluation of Safety, Tolerability, and Efficacy of INZ-701 in ... The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of multiple ascending doses of INZ-701, ...

3. biomarin.com biomarin.com/news/press-releases/biomarin-strengthens-enzyme-therapy-business-with-acquisition-of-inozyme-pharma/

BioMarin Strengthens Enzyme Therapy Business with ... INZ-701 is a potential first-in-class, subcutaneous enzyme replacement therapy that is being developed for infants, pediatric and adult patients ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11454822/

7217 Impact of INZ-701 on Bone and Mineral Metabolism ... 7217 Impact of INZ-701 on Bone and Mineral Metabolism Biomarkers and Clinical Outcomes in Adults with ENPP1 Deficiency - Results from 48-week ...

5. academic.oup.com academic.oup.com/jes/article/8/Supplement_1/bvae163.441/7813475

7217 Impact of INZ-701 on Bone and Mineral Metabolism ... 7217 Impact of INZ-701 on Bone and Mineral Metabolism Biomarkers and Clinical Outcomes in Adults with ENPP1 Deficiency - Results from 48-week ...

6. docs.publicnow.com docs.publicnow.com/viewDoc.aspx?filename=181971%5CEXT%5C5D363F92C13799B9836A0E857F2B20660C312A56_90A41819396594EE5A7AF9AF5A826B81D7E61EB1.PDF

Interim clinical and safety data of INZ-701 treatment in infants ... Living with ENPP1. Deficiency. Interim clinical and safety data of INZ-701 treatment in infants and young children with ENPP1 Deficiency and key program ...

7. inozyme.com inozyme.com/scientific-focus/our-science/

Our Science So far, clinical data have shown that INZ-701 was generally safe and well tolerated and that it meaningfully increased PPi levels in multiple clinical trials.