NCT06739980撤回2 期
The ENABLE Study: An Open-Label, Long-Term Safety and Efficacy Study of INZ-701 in Patients With Ectonucleotide Pyrophosphatase/ Phosphodiesterase 1 (ENPP1) Deficiency
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 40
- 主要终点
- Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) concentration through Week 52
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Individuals eligible to participate must meet all of the following inclusion criteria:
- •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)
- •Provide assent in accordance with local regulations, if <18 years of age
- •Male or female, ≥1 year of age
- •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
- •Must have at least one of the following clinical signs and/or symptoms consistent with ENPP1 Deficiency:
- •≥1 atraumatic vertebral fracture
- •≥2 fractures as an adult (eg, long bones, digits, vertebrae)
- •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)
- •History of myocardial infarction, unstable angina, transient ischemic attack, or low cardiac output before the age of 40 years
- •Renal vascular hypertension or other evidence for vascular insufficiency/stenosis
- •History of rickets or bone deformity
- •Diagnosis of ossification of the posterior longitudinal ligament
- •Other clinical signs/symptoms, with approval by Inozyme
- •Fasting plasma PPi concentration of <1400 nM at Screening
- •Serum level of 25-hydroxyvitamin D (25[OH]D) ≥12 ng/mL at Screening (Participants may be rescreened after receiving cholecalciferol treatment.)
- •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
- •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
- •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)
- •In the opinion of the Investigator, able to complete all aspects of the study
排除标准
- •Individuals who meet any of the following exclusion criteria will not be eligible to participate:
- •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
- •Eligible for another Inozyme sponsored study of INZ-701 treatment that is open for enrollment
- •Receiving prohibited medications
- •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
- •Received previous treatment with INZ-701
- •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
- •Pregnant, trying to become pregnant, or breastfeeding
- •Male participants trying to father a child
研究组 & 干预措施
INZ-701
Experimental
INZ-701 will be administered by SC injection on a once-weekly basis as follows:
- Study participants from 1 year to <18 years of age will receive a dose of 2.4 mg/kg
- Study participants ≥18 years and:
weighing <50 kg or >100 kg will receive a 1.8 mg/kg dose,
OR
weighing ≥50 and ≤100 kg will receive a 150 mg dose of INZ-701
干预措施: INZ-701 (Drug)
结局指标
主要结局
Change from Baseline in Plasma Inorganic Pyrophosphate (PPi) concentration through Week 52
时间窗: 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.
次要结局
- Change from Baseline in skeletal abnormalities as measured by the Radiographic Global Impression of Change (RGI-C) global score through Week 104 for patients 1 to <13 years(52 weeks (Baseline through Week 52))
- Change from Baseline in Rickets Severity Score (RSS) total score through Week 104 (measured on all long bones with open growth plates in the knee or wrist) for patients 1 to <13 years(104 weeks (Baseline through Week 104))
- Change from Baseline in arterial calcification score based on low dose computed tomography (CT) through Week 104 for patients 1 to <18 years(104 weeks (Baseline through Week 104))
- Change over time in serum biomarkers: Fibroblast growth factor 23 for patients >1 year(104 weeks (Baseline through Week 104))
- Change over time in serum biomarkers: Procollagen type 1 N-terminal propeptide for patients >1 year(104 weeks (Baseline through Week 104))
- Change over time in serum biomarkers: Bone-specific alkaline phosphatase for patients >1 year(104 weeks (Baseline through Week 104))
- Change over time in serum biomarkers: Carboxy terminal cross-linked telopeptide of type I collagen for patients >1 year(104 weeks (Baseline through Week 104))
- Change from Baseline in growth parameters (body weight expressed as Z-score) through Week 104 for patients 1 to <13 years(104 weeks (Baseline through Week 104))
- Change over time in serum biomarkers: Serum phosphate for patients >1 year(104 weeks (Baseline through Week 104))
- Change from Baseline in growth parameters (height/length expressed as Z-score) through Week 104 for patients 1 to <13 years(104 weeks (Baseline through Week 104))
- Change from Baseline over time in growth velocity as measured by height over time through Week 104 for patients 1 to <13 years(104 weeks (Baseline through Week 104))
- Change from Baseline in lower extremity angle measurements from radiographic x-rays through Week 104 for patients 1 to <13 years(104 weeks (Baseline through Week 104))
- Change from Baseline in audiometric outcomes as measured by hearing tests through Week 104 for patients 1 to <18 years(104 weeks (Baseline through Week 104))
- Change from Baseline in 6 Minute Walk Test (6MWT) for patients >5 years(104 weeks (Baseline through Week 104))
- Change in Baseline in bone mineral content and bone mineral density Z-score via dual X-ray absorptiometry (DXA) scan through Week 104 for patients ≥13 years(104 weeks (Baseline through Week 104))
- Change from Baseline in age-appropriate motor performance-mobility assessments through Week 104 (Peabody Developmental Motor Scale - third edition [PDMS] for patients 1 to < 5 years(104 weeks (Baseline through Week 104))
- Patient Reported Outcomes (PROs) through Week 104 assessed via Patient-Reported Outcome Measurement Information System (PROMIS) Pediatric - Cognitive Function, Fatigue, Pain Intensity, Pain Interference, Mobility) for patients 1 to <18 years(104 weeks (Baseline through Week 104))
- PROs through Week 104 (Patient-Reported Outcome Measurement Information System [PROMIS] Pediatric - Cognitive Function, Fatigue, Pain Intensity, Pain Interference, Physical Function) for patients >17 years(104 weeks (Baseline through Week 104))
- PROs through Week 104 (Clinical-, Caregiver-, and Patient-reported Global Impression of Change [CGI-C, CaGI-C, and PGI-C for patients >17 years(104 weeks (Baseline through Week 104))
- Change from Baseline in bone histomorphometry as measured by bone biopsy through Week 104 for patients >17 years(104 weeks (Baseline through Week 104))
- Change from Baseline in pain visual analog VAS) score through Week 104 for patients >17 years(104 weeks (Baseline through Week 104))
研究者
相似试验
进行中（未招募）
2 期
ADAPT Study: Long-term Safety Study of INZ-701 in Patients With ENPP1 Deficiency and ABCC6 DeficiencyGene MutationsArterial CalcificationEctonucleotide Pyrophosphatase/phosphodiesterase1 DeficiencyAutosomal Recessive Hypophosphatemic Rickets Type 2Pseudoxanthoma ElasticumNCT06462547Inozyme Pharma22
进行中（未招募）
1 期
The ENERGY Study: Evaluation of Safety and Tolerability of INZ-701 in Infants With ENPP1 Deficiency or ABCC6 DeficiencyEctonucleotide Pyrophosphatase/phosphodiesterase1 DeficiencyAutosomal Recessive Hypophosphatemic RicketsGeneralized Arterial Calcification of InfancyATP-Binding Cassette Subfamily C Member 6 DeficiencyPseudoxanthoma ElasticumNCT05734196Inozyme Pharma16
已完成
2 期
Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD) Extension Study for Subjects Previously Enrolled in Triheptanoin StudiesCarnitine Palmitoyltransferase (CPT I or CPT II) DeficiencyVery Long Chain Acyl-CoA Dehydrogenase (VLCAD) DeficiencyLong-chain 3-hydroxy-acyl-CoA Dehydrogenase (LCHAD) DeficiencyTrifunctional Protein (TFP) DeficiencyCarnitine-acylcarnitine Translocase (CACT) DeficiencyNCT02214160Ultragenyx Pharmaceutical Inc94
终止
1 期
A Study of ZW171 in Participants With Advanced or Metastatic Mesothelin-expressing CancersMesothelin-expressing Advanced CancersNCT06523803Zymeworks BC Inc.32
已完成
3 期
A Trial of E7777 in Persistent and Recurrent Cutaneous T-Cell LymphomaPersistent or Recurrent Cutaneous T-Cell LymphomaNCT01871727Eisai Inc.112