INZ-701 for Metabolic Bone Disease

(ENERGY Trial)

Recruiting at 6 trial locations

Overseen By Inozyme Clinical Trial Information

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Inozyme Pharma

Disqualifiers: Uncontrolled thyroid disease, Malignancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called INZ-701 for infants with certain metabolic bone diseases, specifically ENPP1 Deficiency or ABCC6 Deficiency. The main goal is to determine if INZ-701 is safe and tolerable for infants. The trial adjusts doses based on participants' responses, starting with small doses and potentially increasing them. Infants diagnosed with these conditions and showing symptoms like heart problems or breathing issues might be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications. However, if you are participating in another study or have recently taken another investigational drug, you may need to wait before joining this trial.

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 past studies, individuals with ENPP1 Deficiency and ABCC6 Deficiency did not experience major side effects from the treatment. Additionally, INZ-701 has shown promise in raising PPi levels, which are crucial for healthy bones and minerals. This suggests the treatment could be both effective and safe for those with these conditions. Although the current trial remains in its early stages, previous results encourage confidence in the safety of INZ-701. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about INZ-701 for metabolic bone disease because it represents a novel approach to treatment by targeting an enzyme deficiency. Unlike current therapies that primarily focus on symptom management, INZ-701 aims to address the root cause by compensating for the lack of a specific enzyme involved in bone metabolism. This mechanism could potentially lead to more effective and long-lasting results. Additionally, the dosing flexibility, with various levels being tested, may help optimize treatment based on individual patient needs.

What evidence suggests that INZ-701 might be an effective treatment for metabolic bone disease?

Research has shown that INZ-701, the investigational treatment in this trial, may help treat conditions linked to ENPP1 Deficiency and ABCC6 Deficiency. In earlier studies, INZ-701 was generally safe and increased levels of PPi, a type of phosphate important for healthy bones. These results suggest that INZ-701 could improve bone and mineral health, which is vital for patients with these conditions. Although more research is needed, early findings are promising for those considering participation in this trial. ^{1 5 6 7 8}

Who Is on the Research Team?

Alex Lai, MD

Principal Investigator

Inozyme Pharma

Are You a Good Fit for This Trial?

The ENERGY study is for infants weighing at least 0.5 kg with a genetic diagnosis of ENPP1 Deficiency, which can cause rickets and other related conditions. Infants must be between 1 month to less than 1 year old and able to complete the study procedures. Caregivers must consent and provide medical records access.

Inclusion Criteria

Caregiver(s) must provide written or electronic consent after the nature of the study has been explained, and prior to any research-related procedures, per International Conference on Harmonisation (ICH) Good Clinical Practice (GCP).

In the opinion of the Investigator, the subject must be able to complete all aspects of the study

I have a confirmed genetic diagnosis of ENPP1 Deficiency.

Exclusion Criteria

I have been diagnosed with cancer.

According to the doctor, you have a serious disease or abnormal test results that could affect your participation in the study or make it hard to understand the study results. This includes uncontrolled thyroid disease or other unrelated bone, muscle, or tissue diseases.

I am not in another drug study or haven't taken any experimental drugs recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

8 weeks

Treatment

Participants receive INZ-701 for safety, tolerability, pharmacokinetics, and pharmacodynamics assessment

52 weeks

Twice weekly visits for dosing

End of Treatment (EOT)

Participants have a final visit 30 days after the last dose of INZ-701

4 weeks

Extension

Participants may continue to receive INZ-701 until it is commercially available or an alternative study is available

Follow-up

Participants are monitored for survival outcomes at least quarterly through the end of the study

What Are the Treatments Tested in This Trial?

Interventions

• INZ-701

Trial Overview This trial tests the safety and tolerability of a medication called INZ-701 in infants diagnosed with ENPP1 Deficiency, which affects bone development and can lead to rickets or vascular calcification.

How Is the Trial Designed?

Group I: INZ-701 Experimental Treatment 1 Intervention

The first 2 study participants will receive 1 dose of 0.2 mg/kg on Day 1 and start at Dose Level A (0.2 mg/kg twice weekly) on Day 8. The Data Review Committee (DRC) comprised of representatives of the Sponsor, the study Investigators, and a physician who is a subject matter expert not affiliated with the study or Sponsor, will review the safety data of the first study participant through Day 8. Contingent upon this review, the Sponsor will decide if additional study participants can begin receiving INZ-701. After the second study participant completes Day 32, the DRC will perform a cumulative review of safety and PK/PD data and will make dosing recommendations, for example, modifying the dose of the ongoing study participants and/or changing the starting dose for future participants. Dose Level A: 0.2 mg/kg twice weekly Dose Level B: 0.6 mg/kg twice weekly Dose Level C: 0.2 mg/kg once weekly Dose Level D: 0.6 mg/kg once weekly Dose Level E: 1.8 mg/kg once weekly

Who Is Running the Clinical Trial?

Inozyme Pharma

Lead Sponsor

Trials

10

Recruited

1,400+

Published Research Related to This Trial

INZ-701, a human ENPP1-Fc protein, shows promise as an enzyme replacement therapy for ENPP1 deficiency, effectively restoring pyrophosphate (PPi) levels and preventing ectopic calcification in a mouse model over an 8-week treatment period.

The treatment not only improved growth and corrected bone defects in ENPP1-deficient mice but also significantly reduced mortality, highlighting its potential efficacy in addressing the severe symptoms associated with conditions like generalized arterial calcification of infancy (GACI) and autosomal-recessive hypophosphatemic rickets type 2 (ARHR2).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

INZ-701 Prevents Ectopic Tissue Calcification and Restores Bone Architecture and Growth in ENPP1-Deficient Mice. Cheng, Z., O'Brien, K., Howe, J., et al.[2021]

Conventional therapy for ARHR2 patients improves rickets symptoms but does not increase bone mineral density (BMD), and half of the treated patients developed medullary nephrocalcinosis, indicating potential risks associated with phosphate supplementation.

In contrast, treatment with recombinant Enpp1-Fc protein in ENPP1-deficient mice not only normalized trabecular bone mass and improved bone strength but also prevented nephrocalcinosis, suggesting that enzyme replacement therapy could be a safer and more effective option for increasing bone mass in ARHR2 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice. Ferreira, CR., Kavanagh, D., Oheim, R., et al.[2022]

Heterozygous mutations in the ENPP1 gene can lead to early onset osteoporosis in adults, characterized by fractures and low bone mineral density, indicating a gene dose effect on bone health.

The study found that individuals with ENPP1 deficiency had elevated FGF23 levels and hypophosphatemia, similar to findings in mice with ENPP1 deficiency, suggesting a shared mechanism affecting bone mineralization and structural integrity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Heterozygous ENPP1 Deficiency Is Associated With Early Onset Osteoporosis, a Phenotype Recapitulated in a Mouse Model of Enpp1 Deficiency. Oheim, R., Zimmerman, K., Maulding, ND., et al.[2022]

ENPP1 deficiency leads to osteoporosis through mechanisms that suppress Wnt signaling pathways, rather than through reduced bone volume, as shown in studies of Enpp1asj/asj mice compared to wild-type siblings.

The skeletal phenotype in younger ENPP1 deficient mice is driven by non-catalytic functions of ENPP1, while older mice show that low levels of extracellular pyrophosphate (PPi) contribute to bone issues, indicating a complex relationship between ENPP1 function and bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic pathways disrupted by ENPP1 deficiency provide insight into mechanisms of osteoporosis, osteomalacia, and paradoxical mineralization. Maulding, ND., Kavanagh, D., Zimmerman, K., et al.[2022]

In a study using genetically modified mice, the removal of the Nmp4 gene from mesenchymal stem/progenitor cells significantly enhanced the bone-building effects of parathyroid hormone (PTH), indicating that targeting this gene could improve osteoporosis treatments.

The research showed that while Nmp4 deletion in osteocytes increased bone volume, it did not enhance the response to PTH, suggesting that the timing and type of cell targeted are crucial for maximizing the effectiveness of bone anabolic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conditional Loss of Nmp4 in Mesenchymal Stem Progenitor Cells Enhances PTH-Induced Bone Formation. Atkinson, EG., Adaway, M., Horan, DJ., et al.[2023]

The study identified Inpp4bα as a crucial regulator of osteoclast differentiation, with its expression linked to both the early and activation stages of osteoclasts, impacting bone mass.

Mice lacking Inpp4b showed increased osteoclast differentiation and reduced bone mass, indicating that INPP4B is a significant gene associated with osteoporosis risk in both mice and humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inositol polyphosphate 4-phosphatase B as a regulator of bone mass in mice and humans. Ferron, M., Boudiffa, M., Arsenault, M., et al.[2021]

Citations

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

7217 Impact of INZ-701 on Bone and Mineral Metabolism ... Purpose: To describe the safety, tolerability, immunogenicity, and exploratory efficacy (bone and mineral metabolism biomarkers and clinical ...

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

Inozyme Pharma Announces Positive Interim Data from ... INZ-701 was generally safe and well tolerated and meaningfully increased PPi levels in patients with ENPP1 Deficiency and ABCC6 Deficiency.

3. checkrare.com checkrare.com/enpp1-and-abcc6-deficiency-data-presented-at-asbmr-2024/

ENPP1 and ABCC6 Deficiency Data Presented at ASBMR ... Kurt Gunter, MD, Inozyme Pharma, discusses data presented on ENPP1 deficiency and ABCC6 deficiency at ASBMR 2024.

4. 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, ...

5. synapse.patsnap.com synapse.patsnap.com/article/inozyme-to-present-phase-12-inz-701-data-for-enpp1-and-pxe-at-medical-conferences

Inozyme to Present Phase 1/2 INZ-701 Data for ENPP1 ... The open-label Phase 2 extension is designed to evaluate long-term safety and efficacy over a 48-week period, with a focus on skeletal, vascular ...

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

7217 Impact of INZ-701 on Bone and Mineral Metabolism ... No targeted therapy exists for this disease. INZ-701 is a recombinant ENPP1-Fc investigational product. Purpose: To describe the safety ...

7. 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.

8. checkrare.com checkrare.com/investigational-therapy-inz-701-for-enpp1-deficiency/

Investigational Therapy INZ-701 for ENPP1 Deficiency INZ-701 is a subcutaneous investigational ENPP1 enzyme replacement therapy (ERT). It is currently in development for the treatment of ENPP1 deficiency, ABCC6 ...