INZ-701 for Pseudoxanthoma Elasticum and Arterial Calcification

Recruiting at 5 trial locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Inozyme Pharma

Disqualifiers: Pregnancy, Breastfeeding, Other clinical study, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of this study (Study INZ701-304 \[ADAPT\]) is to assess the long-term safety of INZ-701 in patients with ENPP1 Deficiency or ABCC6 Deficiency who have received INZ-701 in an existing clinical study and choose to continue dosing for the potential treatment of their condition.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug INZ-701 for treating Pseudoxanthoma Elasticum?

Research shows that INZ-701, a drug that increases levels of a natural substance called pyrophosphate, can reduce unwanted calcium deposits in a mouse model of Pseudoxanthoma Elasticum, suggesting it might help treat this condition in humans. ^{1 2 3 4 5}

How is the drug INZ-701 unique in treating Pseudoxanthoma Elasticum?

INZ-701 is unique because it is a recombinant enzyme that increases plasma levels of pyrophosphate (PPi), a natural inhibitor of calcification, which is deficient in Pseudoxanthoma Elasticum patients. This approach targets the underlying cause of the disease, unlike other treatments that may only address symptoms. ^{1 3 5 6 7}

Research Team

Kurt Gunter, MD

Principal Investigator

Inozyme Pharma, Inc.

Eligibility Criteria

The ADAPT study is for males and females over 1 year old with ENPP1 or ABCC6 Deficiency who have previously taken INZ-701 in a clinical trial. They must be able to complete the study, provide consent (or assent if under 18), and use effective contraception.

Inclusion Criteria

I have given my written or electronic consent to participate in the study.

I can participate in all parts of the study as required.

I agree to use condoms and not donate sperm during and 30 days after my treatment.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive once-weekly subcutaneous doses of INZ-701

Until INZ-701 is commercially available or development is discontinued

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Open-label extension

Participants continue dosing for long-term safety assessment

6 years

Treatment Details

Interventions

• INZ-701 (Other)

Trial Overview This trial tests the long-term safety of INZ-701, a potential treatment for conditions like Pseudoxanthoma Elasticum and various forms of Hypophosphatemic Rickets associated with ENPP1 or ABCC6 genetic mutations.

Participant Groups

Group I: INZ-701 Experimental Treatment 1 Intervention

INZ-701 will be administered by subcutaneous injection on a once-weekly basis as follows: * Study participants from 1 year to \<13 years of age will receive a dose of 2.4 mg/kg * Study participants ≥13 years will either receive a 1.8 mg/kg dose or a 150 mg flat dose of INZ-701

Who Is Running the Clinical Trial?

Inozyme Pharma

Lead Sponsor

Trials

10

Recruited

1,400+

Findings from Research

Restoring plasma levels of inorganic pyrophosphate (PPi) using INZ-701, a recombinant human ENPP1 protein, significantly reduced ectopic calcification in a mouse model of pseudoxanthoma elasticum (PXE), indicating its potential as a therapeutic approach.

The treatment with INZ-701 not only increased PPi levels but also correlated with decreased calcification in specific tissues, suggesting that enhancing PPi could effectively inhibit the calcification process associated with PXE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

INZ-701, a recombinant ENPP1 enzyme, prevents ectopic calcification in an Abcc6-/- mouse model of pseudoxanthoma elasticum. Jacobs, IJ., Cheng, Z., Ralph, D., et al.[2023]

In a two-year study using PET/CT scans with 18F-NaF, calcification in the arterial walls of patients with pseudoxanthoma elasticum progressed, indicating ongoing vascular changes associated with the disease.

However, the active microcalcification in the skin showed reduced deposition over time, suggesting that while vascular calcification continues, skin microcalcification may stabilize, making it a potential surrogate marker for monitoring the disease in future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous and Vascular Deposits of 18F-NaF by PET/CT in the Follow-Up of Patients with Pseudoxanthoma Elasticum. Lillo, E., Gutierrez-Cardo, A., Murcia-Casas, B., et al.[2021]

In a study of 107 patients with pseudoxanthoma elasticum (PXE), researchers found that low levels of plasma pyrophosphate (PPi) are present in PXE patients, but PPi levels do not correlate significantly with arterial calcification or disease severity.

The study revealed that age is the primary factor influencing disease severity and calcification in PXE, rather than PPi levels, suggesting that PPi is not a reliable biomarker for monitoring disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationships between Plasma Pyrophosphate, Vascular Calcification and Clinical Severity in Patients Affected by Pseudoxanthoma Elasticum. Leftheriotis, G., Navasiolava, N., Clotaire, L., et al.[2023]

Reconstituting the ABCC6 gene in a mouse model of pseudoxanthoma elasticum led to increased levels of pyrophosphate, which is crucial for preventing ectopic mineralization, demonstrating a potential therapeutic approach.

Early intervention with adenovirus-mediated ABCC6 gene delivery significantly reduced skin mineralization in young mice, suggesting that this method could be an effective preventive therapy for these genetic disorders, although it was ineffective in older mice with established mineral deposits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adenovirus-Mediated ABCC6 Gene Therapy for Heritable Ectopic Mineralization Disorders. Huang, J., Snook, AE., Uitto, J., et al.[2021]

In a study of 273 patients with pseudoxanthoma elasticum (PXE) and 125 hospital controls, the prevalence of kidney stones was found to be similar between the two groups, with 6.9% of PXE patients and 5.6% of controls having stones.

The analysis showed no significant increased odds of kidney stones in PXE patients compared to controls, suggesting that diminished plasma pyrophosphate levels in PXE do not lead to a higher risk of kidney stone formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do pseudoxanthoma elasticum patients have higher prevalence of kidney stones on computed tomography compared to hospital controls? Harmsen, IM., Kok, M., Bartstra, JW., et al.[2023]

A study of 104 patients with pseudoxanthoma elasticum (PXE) revealed that they have significantly higher rates of arterial calcifications compared to 93 hospital controls, particularly in the intracranial internal carotid artery, arms, and lower legs.

The severity of arterial calcifications in PXE patients was also greater, indicating a distinct vascular phenotype associated with the disorder, which could have implications for their overall cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence and severity of arterial calcifications in pseudoxanthoma elasticum (PXE) compared to hospital controls. Novel insights into the vascular phenotype of PXE. Kranenburg, G., de Jong, PA., Mali, WP., et al.[2018]

A 37-year-old man with atypical pseudoxanthoma elasticum (PXE) presented severe arterial calcifications but minimal skin and eye lesions, highlighting the diverse manifestations of PXE and its overlap with other vascular calcification disorders.

Genetic screening revealed variants in the ABCC6 gene, suggesting a need for a specialized next-generation sequencing panel to enhance the diagnosis of vascular calcification disorders, including PXE and related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pseudoxanthoma elasticum with prominent arterial calcifications evoking CD73 deficiency. Devriese, M., Legrand, A., Courtois, MC., et al.[2019]

References

1. Denmark pubmed.ncbi.nlm.nih.gov

INZ-701, a recombinant ENPP1 enzyme, prevents ectopic calcification in an Abcc6-/- mouse model of pseudoxanthoma elasticum. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Cutaneous and Vascular Deposits of 18F-NaF by PET/CT in the Follow-Up of Patients with Pseudoxanthoma Elasticum. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Relationships between Plasma Pyrophosphate, Vascular Calcification and Clinical Severity in Patients Affected by Pseudoxanthoma Elasticum. [2023]

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

Adenovirus-Mediated ABCC6 Gene Therapy for Heritable Ectopic Mineralization Disorders. [2021]

5. Japan pubmed.ncbi.nlm.nih.gov

Do pseudoxanthoma elasticum patients have higher prevalence of kidney stones on computed tomography compared to hospital controls? [2023]

6. Ireland pubmed.ncbi.nlm.nih.gov

Prevalence and severity of arterial calcifications in pseudoxanthoma elasticum (PXE) compared to hospital controls. Novel insights into the vascular phenotype of PXE. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Pseudoxanthoma elasticum with prominent arterial calcifications evoking CD73 deficiency. [2019]