Clinical trial NCT06046820: The ENERGY 3 Study: Evaluation of Efficacy and Safety of INZ-701 in Children With ENPP1 Deficiency
Official title: The ENERGY 3 Study: A Randomized, Controlled, Open-Label, Phase 3 Study to Evaluate the Efficacy and Safety of INZ-701 in Children With Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) Deficiency
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Ectonucleotide Pyrophosphatase/Phosphodiesterase1 Deficiency
Autosomal Recessive Hypophosphatemic Rickets
Generalized Arterial Calcification of Infancy
Keywords: Ectonucleotide Pyrophosphatase/Phosphodiesterase1 Deficiency
Hypopyrophosphatemia
ENPP1
Autosomal Recessive Hypophosphatemic Rickets Type 2
ARHR2
Generalized Arterial Calcification of Infancy
GACI
Lead sponsor: Inozyme Pharma
Sponsor class: INDUSTRY
First posted: 2023-09-21
Enrollment: 27
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) concentration through Week 52
timeFrame: 52 weeks (Baseline through Week 52)
Secondary outcomes:
measure: Change from Baseline in skeletal abnormalities as measured by the Radiographic Global Impression of Change (RGI-C) global score through Week 52
timeFrame: Baseline, Week 26, Week 52
measure: Change from Baseline in rickets as measured by Rickets Severity Score (RSS) total score through Week 52
timeFrame: Baseline, Week 26, Week 52
measure: Change from Baseline in growth Z-score (height/body length and weight) through Week 52
timeFrame: Baseline, Day 29, Week 8, Week 13, Week 26, Week 39, Week 52
measure: Area under the Plasma Concentration versus Time Curve (AUC) of INZ-701
timeFrame: 52 weeks (Randomized Treatment Period)
measure: Maximum Plasma Concentration (Cmax) of INZ-701
timeFrame: 52 weeks (Randomized Treatment Period)
measure: Change from Baseline in ENPP1 activity (µM/min) through week 52
timeFrame: 52 weeks (Randomized Treatment Period)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
city: Montréal
country: Canada
facility: Centre Hospitalier Universitaire (CHU) Sainte-Justine
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital Bicêtre, Service d'endocrinologie et diabète de l'enfant (Childhood Endocrinology and Diabetes Department)
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital and Research Centre
city: Barcelona
country: Spain
facility: Hospital San Joan de Deu
city: Istanbul
country: Turkey
facility: Umraniye Training and Research Hospital
city: Sarıçam
country: Turkey
facility: Cukurova Universitesi Tip Fakultesi
city: Dubai
country: United Arab Emirates
facility: Al Jalila Children's Specialty Hospital
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
Study officials:
affiliation: Inozyme Pharma, Inc.
name: Kurt Gunter, MD
role: STUDY_DIRECTOR
References: