the enable study: safety and efficacy study of inz-701 in patients with enpp1 deficiency

Conditions: Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency; Autosomal Recessive Hypophosphatemic Rickets; Generalized Arterial Calcification of Infancy 1

Summary: 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 who have not previously received inz-701 and are not eligible for existing inozyme-sponsored clinical studies that are still open to enrollment.

inz-701 is an ectonucleotide pyrophosphatase/phosphodiesterase 1 (enpp1) enzyme replacement therapy in development for the treatment of the ultra-rare genetic disorder, enpp1 deficiency. study inz701-108 (enable) is an open-label study to assess the long-term safety and efficacy of inz-701 in patients 1 year of age and older with enpp1 deficiency who have not previously received inz-701 and are not eligible for an inozyme-sponsored clinical study that is open to recruitment. the study will consist of a 30-day screening period, followed by an open-label treatment period during which all participants will receive once-weekly subcutaneous (sc) doses of inz-701 and continue treatment through 104 weeks. the dose will be determined by the participant's age and weight.

Eligibility criteria:
inclusion criteria: individuals eligible to participate must meet all of the following inclusion criteria: 1. provide written or electronic informed consent after the nature of the study has been explained, and prior to any research-related procedures, per international council for harmonisation of technical requirements for pharmaceuticals for human use (ich) good clinical practice (gcp) 2. provide assent in accordance with local regulations, if \<18 years of age 3. male or female, ≥1 year of age 4. a confirmed postnatal molecular genetic diagnosis of enpp1 deficiency with biallelic variants (ie, homozygous or compound heterozygous) performed using assays that meet ce-marked requirements, or from a college of american pathologists/clinical laboratory improvement amendments (cap/clia) certified laboratory, or regional equivalent 5. must have at least one of the following clinical signs and/or symptoms consistent with enpp1 deficiency: 1. ≥1 atraumatic vertebral fracture 2. ≥2 fractures as an adult (eg, long bones, digits, vertebrae) 3. for participants \<55 years of age, low bone mineral density measured at any of the following sites: lumbar spine, radius, and hip (dxa z-score less than -1.5) 4. history of myocardial infarction, unstable angina, transient ischemic attack, or low cardiac output before the age of 40 years 5. renal vascular hypertension or other evidence for vascular insufficiency/stenosis 6. history of rickets or bone deformity 7. diagnosis of ossification of the posterior longitudinal ligament 8. other clinical signs/symptoms, with approval by inozyme 6. fasting plasma ppi concentration of \<1400 nm at screening 7. serum level of 25-hydroxyvitamin d (25\[oh\]d) ≥12 ng/ml at screening (participants may be rescreened after receiving cholecalciferol treatment.) 8. women of childbearing potential (wocbp, as defined in clinical trials coordination group \[ctcg 2024\]) must have a negative serum pregnancy test at screening and must not be breastfeeding 9. males who are sexually active must agree to use condoms from the period following first dose of inz-701 through 30 days after the last dose of inz-701 10. wocbp and partners of fertile males who are wocbp must be using or agree to use a highly effective form of contraception (as per ctcg 2024) from at least 1 month before the first dose of inz-701 through 30 days after the last dose of inz701 (greater than 5 half-lives of inz-701) 11. in the opinion of the investigator, able to complete all aspects of the study exclusion criteria: individuals who meet any of the following exclusion criteria will not be eligible to participate: 1. in the opinion of the investigator, presence of any clinically significant disease or laboratory abnormality not due to enpp1 deficiency that may confound interpretation of study results 2. eligible for another inozyme sponsored study of inz-701 treatment that is open for enrollment 3. receiving prohibited medications 4. unable or unwilling to discontinue calcitriol or other active forms of vitamin d3 (or analogs) within 7 days prior to day 1 and/or oral phosphate supplements within 36 hours prior to day 1 5. received previous treatment with inz-701 6. concurrent participation in another interventional clinical study and/or has received an investigational drug within 5 half-lives or within 4 weeks prior to the first dose of inz-701, whichever is longer 7. pregnant, trying to become pregnant, or breastfeeding 8. male participants trying to father a child

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