The ENERGY 3 Study: Evaluation of Efficacy and Safety of INZ-701 in Children With ENPP1 Deficiency

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 exclusion criteria will not be eligible to participate in the study:

1. 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
2. If receiving any of the following prohibited medications as indicated in the protocol: systemic corticosteroids (>5 mg prednisone equivalent per day), anti-fibroblast growth factor 23 (FGF23), and oral and/or IV bisphosphonates
3. Unable or unwilling to discontinue calcitriol or other active forms of vitamin D3 (or analogs) within 7 days prior to Study Day 1 and/or oral phosphate supplements within 36 hours prior to Study Day 1 if randomized to the INZ-701 arm
4. Planned orthopedic surgery that may confound the interpretation of study results during the 52-week Randomized Treatment Period
5. Known intolerance to INZ-701 or any of its excipients
6. A positive COVID-19 test within 5 days prior to Randomization, only if required as per local regulations or institutional policy
7. Previous treatment with INZ-701
8. Concurrent participation in another interventional clinical study and/or has received an investigational drug within 5 half-lives of the last dose or within 4 weeks prior to Randomization, whichever is longer, or use of an investigational device