Autosomal Recessive Hypophosphatemic Rickets, Ectonucleotide Pyrophosphatase/Phosphodiesterase1 Deficiency, Generalized Arterial Calcification of Infancy
Conditions
Keywords
Ectonucleotide Pyrophosphatase/Phosphodiesterase1 Deficiency, Hypopyrophosphatemia, ENPP1, Autosomal Recessive Hypophosphatemic Rickets Type 2, ARHR2, Generalized Arterial Calcification of Infancy, GACI
Brief summary
The primary purpose of Study INZ701-106 (The ENERGY 3 Study) is to assess the efficacy and safety of INZ-701 in children with ENPP1 Deficiency.
Detailed description
INZ-701 is an ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzyme replacement therapy (ERT) in development for the treatment of ENPP1 Deficiency, an ultra-rare genetic disorder with an incidence of 1 in 64,000 pregnancies. Study INZ701-106 (The ENERGY 3 Study) is a multi-center, randomized in a 2:1 ratio, controlled, open-label Phase 3 study to evaluate the efficacy and safety of INZ-701 in children with ENPP1 Deficiency. The study will consist of a Screening Period of up to 52 days (including a washout period of up to 7 days for prohibited medications post-Randomization) and a Randomized Treatment Period (INZ-701 or control) of 52 weeks, followed by an Open-label Extension Period during which all study participants may receive INZ-701, and an End of Study (EOS) Safety visit 30 days after the last dose of INZ-701.
Interventions
DRUGINZ-701
Recombinant fusion protein that contains the extracellular domains of human ENPP1 coupled with an Fc fragment from an immunoglobulin gamma-1 (IgG1) antibody.
Conventional therapy is defined as oral phosphate supplements and calcitriol or other active forms of vitamin D3 (or analogs). No other agents for treatment of ENPP1 Deficiency are allowed in the control arm.
Sponsors
Inozyme Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Study INZ701-106 (ENERGY 3) is a multicenter, randomized in a 2:1 ratio, controlled, open-label Phase 3 study to evaluate the efficacy and safety of INZ-701 in children with ENPP1 Deficiency.
Eligibility
Sex/Gender
ALL
Age
1 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
Study participants must meet all of the following inclusion criteria: 1. Caregiver's written or electronic informed 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) 2. Study participant's assent in accordance with local regulations 3. A confirmed postnatal molecular genetic diagnosis of ENPP1 Deficiency with biallelic mutations (ie, homozygous or compound heterozygous) performed by a College of American Pathologists/Clinical Laboratory Improvement Amendments (CAP/CLIA) certified laboratory or regional equivalent 4. Males and females ≥1 year and \<13 years of age at Study Day 1 5. Open growth plates of the distal femur and proximal tibia in both legs 6. Plasma PPi concentration of \<1400 nM at Screening 7. 25-hydroxyvitamin D (25\[OH\]D) levels of ≥12 ng/mL at Screening 8. Radiographic evidence of skeletal abnormalities based on an RSS ≥2 9. Female participants of childbearing potential must have a negative serum pregnancy test at Screening and must not be breastfeeding 10. Study participants of childbearing potential who are sexually active must agree to use a highly effective form of contraception in accordance with Clinical Trials Facilitation and Coordination Group (CTFG) guidance and local guidelines for the duration of the study 11. In the opinion of the Investigator, able to complete all aspects of the study
Exclusion criteria
Study participants meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) concentration through Week 52 | 52 weeks (Baseline through Week 52) | For each subject, plasma PPi will be measured via a series of blood samples obtained throughout the study, comparing the subject's baseline value over time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in rickets as measured by Rickets Severity Score (RSS) total score through Week 52 | Baseline, Week 26, Week 52 | The RSS assesses rickets severity by utilizing a scoring system that uses a scale from 0 to 4 for the wrists and 0 to 6 for the knees, to generate a total score of 0 to 10, where 0 is normal and 10 is the worst score possible ie, most severe skeletal abnormalities observed radiographically. |
| Change from Baseline in growth Z-score (height/body length and weight) through Week 52 | Baseline, Day 29, Week 8, Week 13, Week 26, Week 39, Week 52 | A Z-score represents the degree to which that particular measurement for that individual differs from the reference value in the general population. (height/body length and weight) through Week 52 |
| Change from Baseline in skeletal abnormalities as measured by the Radiographic Global Impression of Change (RGI-C) global score through Week 52 | Baseline, Week 26, Week 52 | The RGI-C is an overall radiographic score which can be used to monitor response to a therapeutic intervention comparing scores from 2 time points. A determination of healing on a scale of 0 to +3 with 0 being no change or healing and +3 being complete healing; worsening is also measured on a scale of 0 to -3 with 0 being no change and -3 being severe worsening. |
| Maximum Plasma Concentration (Cmax) of INZ-701 | 52 weeks (Randomized Treatment Period) | For each subject, the maximum concentration of INZ-701 in the plasma will be measured via a series of blood samples obtained throughout the study, comparing the subject's baseline value over time. |
| Change from Baseline in ENPP1 activity (µM/min) through week 52 | 52 weeks (Randomized Treatment Period) | For each subject, the activity of INZ-701 (µM/min) in the serum will be assessed through hydrolysis of a substrate to the enzyme, via a series of blood samples obtained throughout the study, comparing the subject's baseline value over time. |
| Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701 | 52 weeks (Randomized Treatment Period) | For each subject, variation of concentration of INZ-701 in the plasma will be measured via a series of blood samples obtained throughout the study, comparing the subject's baseline value over time. |
Countries
Australia, Canada, France, Saudi Arabia, Spain, Turkey (Türkiye), United Arab Emirates, United Kingdom, United States
Outcome results
None listed