INZ-701 for Pseudoxanthoma Elasticum and Arterial Calcification

Recruiting at 5 trial locations

Overseen By Inozyme Clinical Trial Information

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Inozyme Pharma

Disqualifiers: Pregnancy, Breastfeeding, Other clinical study, others

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

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

Compensation: Varies

Number of Visits: 2

Duration: Until INZ-701 is commercially available or development is discontinued

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the long-term safety of INZ-701, a potential new drug, for individuals with ENPP1 or ABCC6 Deficiency. These conditions can lead to issues like pseudoxanthoma elasticum, affecting the skin and tissues, or arterial calcification, impacting blood vessels. Participants receive a weekly injection of INZ-701 to assess its effectiveness in managing these conditions over time. The trial is open to those who participated in a previous INZ-701 trial for these conditions and wish to continue treatment. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group.

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.

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

Studies have shown that INZ-701 is generally well-tolerated by patients. Research, including ongoing trials at Yale, indicates positive safety results. Most patients did not experience serious side effects, and any reported issues were mild. These trials focus on patients with rare conditions caused by ENPP1 and ABCC6 deficiencies, which lead to calcium buildup in the body.

Currently, researchers are still testing the treatment to ensure its long-term safety. The trial is in Phase 2, indicating that initial safety tests were promising enough to proceed with more detailed studies. This is encouraging, but more data is needed to fully understand the safety of INZ-701 for everyone. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for pseudoxanthoma elasticum and arterial calcification, which usually focus on managing symptoms and slowing disease progression, INZ-701 is designed to directly address the underlying cause of the disease. It works by replacing the missing enzyme, ENPP1, which is crucial for preventing calcification in tissues and blood vessels. Researchers are excited about INZ-701 because it offers a more targeted approach, potentially reducing calcification more effectively than existing therapies. Additionally, INZ-701 is administered through a convenient once-weekly subcutaneous injection, making it easier for patients to manage.

What evidence suggests that INZ-701 might be an effective treatment for Pseudoxanthoma Elasticum and Arterial Calcification?

Research has shown that INZ-701, the investigational treatment studied in this trial, could help treat conditions like pseudoxanthoma elasticum, which involves abnormal calcium buildup in the body. Studies with mice demonstrated that INZ-701, a specially made enzyme, can stop unwanted calcium deposits. In humans, earlier trials showed that this treatment raises levels of a compound called PPi in the blood, which helps control calcium buildup. Positive results from ongoing trials in adults with ABCC6 Deficiency or ENPP1 Deficiency support its potential effectiveness. Overall, these findings suggest that INZ-701 may help manage symptoms related to these conditions by preventing calcium buildup. ^{1 2 6 7 8}

Who Is on the Research Team?

Kurt Gunter, MD

Principal Investigator

Inozyme Pharma, Inc.

Are You a Good Fit for This Trial?

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 meet one of the specific criteria listed.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• INZ-701

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05030831

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, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10077110/

INZ-701, a recombinant ENPP1 enzyme, prevents ectopic ... INZ-701, a recombinant ENPP1 enzyme, prevents ectopic calcification in an Abcc6−/− mouse model of pseudoxanthoma elasticum · Abstract. Pseudoxanthoma elasticum ( ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05734196

NCT05734196 | The ENERGY Study: Evaluation of Safety ... The primary purpose of Study INZ701-104 (the ENERGY study) is to assess the safety and tolerability of INZ-701 in infants with ENPP1 Deficiency or with ABCC6 ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S152500162400652X

Novel treatment for PXE: Recombinant ENPP1 enzyme ... Our previous studies demonstrated that daily or every other day subcutaneous injections of INZ-701 increased plasma PPi levels and completely ...

5. biospace.com biospace.com/inozyme-pharma-announces-positive-topline-data-from-ongoing-phase-1-2-trials-of-inz-701-in-adults-with-abcc6-deficiency-pxe-and-enpp1-deficiency

Inozyme Pharma Announces Positive Topline Data from ... Inozyme Pharma Announces Positive Topline Data from Ongoing Phase 1/2 Trials of INZ-701 in Adults with ABCC6 Deficiency (PXE) and ENPP1 ...

6. go.drugbank.com go.drugbank.com/drugs/DB17629/clinical_trials?conditions=DBCOND0076421%2CDBCOND0135548%2CDBCOND0161755%2CDBCOND0106836&phase=2&purpose=treatment&status=recruiting

INZ-701 Recruiting Phase 2 Trials for Arterial Calcification ... INZ-701 Recruiting Phase 2 Trials for Arterial Calcification / Gene Mutations / Elasticum, Incomplete Pseudoxanthoma / Ectonucleotide Pyrophosphatase/ ...

7. clinicaltrials.eu clinicaltrials.eu/trial/long-term-safety-study-of-inz-701-for-patients-with-enpp1-and-abcc6-deficiencies-including-pseudoxanthoma-elasticum-and-generalized-arterial-calcification-of-infancy/

Long-term Safety Study of INZ-701 for Patients with ENPP1 ... This clinical trial is focused on studying the long-term safety of a treatment called INZ-701 for patients with certain rare conditions.

8. medicine.yale.edu medicine.yale.edu/news-article/new-data-reported-from-trials-of-drug-developed-at-yale-pathology-to-treat-rare-often-fatal-neonatal-disorder/

New Data Reported From Trials of Drug Developed at Yale ... Inozyme Pharma announced positive topline pharmacokinetic, pharmacodynamic and safety data from the ongoing Phase 1/2 clinical trials of INZ-701 ...