the energy 3 study: evaluation of efficacy and safety of inz-701 in children with enpp1 deficiency

Conditions: Ectonucleotide Pyrophosphatase/Phosphodiesterase1 Deficiency; Autosomal Recessive Hypophosphatemic Rickets; Generalized Arterial Calcification of Infancy

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.

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.

Eligibility criteria:
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

Keywords: ectonucleotide pyrophosphatase/phosphodiesterase1 deficiency hypopyrophosphatemia enpp1 autosomal recessive hypophosphatemic rickets type 2 arhr2 generalized arterial calcification of infancy gaci