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This clinical trial studies the long term safety and efficacy of asfotase alfa in children with HPP who completed Study ENB-006-09 (NCT00952484).
Asfotase alfa was formerly referred to as ENB-0040
Hypophosphatasia (HPP) is a life-threatening, genetic, and ultra-rare metabolic disease characterized by defective bone mineralization and impaired phosphate and calcium regulation that can lead to progressive damage to multiple vital organs, including destruction and deformity of bones, profound muscle weakness, seizures, impaired renal function, and respiratory failure. There are limited data available on the natural course of this disease over time, particularly in patients with the juvenile-onset form.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| asfotase alfa | Experimental | asfotase alfa starting dose 3 mg/kg/week SC injection, increased to 6 mg/kg/week SC injection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Asfotase Alfa | Biological |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Skeletal Radiograph Evaluation Using a Qualitative Radiographic Global Impression of Change (RGI-C) Scale Compared to Baseline (Pre-treatment) in Study ENB-006-09. | Evaluation of radiographic change in rickets severity (as assessed by skeletal radiographs of the hands/wrists and knees) from the Baseline of Study ENB-006-09 (NCT00952484) to the End of Study (EOS) visit in Study ENB-008-10 using an ordinal RGI-C scale score. The RGI-C is a 7-point rating scale that ranges from -3 (indicative of severe worsening of HPP associated rickets) to +3 (indicative of complete or near complete healing of HPP associated rickets). The time points will be pre-treatment (Baseline from Study ENB-006-09) to the last radiographic assessment in Study ENB-008-10, which represents at least 72 months of treatment. | At least 72 months of treatment with asfotase alfa |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shriners Hospital for Children | St Louis | Missouri | 63110 | United States | ||
| Children's Hospital Health Sciences Centre |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32417537 | Derived | Simmons JH, Rush ET, Petryk A, Zhou S, Martos-Moreno GA. Dual X-ray absorptiometry has limited utility in detecting bone pathology in children with hypophosphatasia: A pooled post hoc analysis of asfotase alfa clinical trial data. Bone. 2020 Aug;137:115413. doi: 10.1016/j.bone.2020.115413. Epub 2020 May 14. | |
| 27699270 | Derived |
| Label | URL |
|---|---|
| Hypophosphatasia Website | View source |
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The main criteria for inclusion in Study ENB-006-09 were patients ages 5 to 12 years inclusive, with open growth plates at time of study entry and a documented diagnosis of HPP. To enter the extension, Study ENB-008-10, patients had to successfully complete Study ENB-006-09 and provide consent.
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| ID | Title | Description |
|---|---|---|
| FG000 | 2 mg/kg Asfotase Alfa | The starting dose of asfotase alfa was 3 mg/kg/week for all patients in Study ENB-008-10 and was subsequently increased per study-wide dose adjustment to a total dose of 6 mg/kg/week. Results are shown by the patient's dose group assignment from Study ENB-006-09. |
| FG001 | 3 mg/kg Asfotase Alfa | The starting dose of asfotase alfa was 3 mg/kg/week for all patients in Study ENB-008-10 and was subsequently increased per study-wide dose adjustment to a total dose of 6 mg/kg/week. Results are shown by the patient's dose group assignment from Study ENB-006-09. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 2 mg/kg Asfotase Alfa | Dose group shown is as per patient's randomization in Study ENB-006-09 |
| BG001 | 3 mg/kg Asfotase Alfa | Dose group shown is as per patient's randomization in Study ENB-006-09 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age at Enrollment |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Skeletal Radiograph Evaluation Using a Qualitative Radiographic Global Impression of Change (RGI-C) Scale Compared to Baseline (Pre-treatment) in Study ENB-006-09. | Evaluation of radiographic change in rickets severity (as assessed by skeletal radiographs of the hands/wrists and knees) from the Baseline of Study ENB-006-09 (NCT00952484) to the End of Study (EOS) visit in Study ENB-008-10 using an ordinal RGI-C scale score. The RGI-C is a 7-point rating scale that ranges from -3 (indicative of severe worsening of HPP associated rickets) to +3 (indicative of complete or near complete healing of HPP associated rickets). The time points will be pre-treatment (Baseline from Study ENB-006-09) to the last radiographic assessment in Study ENB-008-10, which represents at least 72 months of treatment. | Each visit in Study ENB-008-10 was calculated relative to the start of exposure to asfotase alfa in Study ENB-006-09 (NCT00952484); 24 weeks are added to each visit in Study ENB-008-10. Results shown are for the last assessment in Study ENB-008-10 and represent at least 72 months of treatment with asfotase alfa. | Posted | Median | Full Range | units on a scale | At least 72 months of treatment with asfotase alfa |
Treatment emergent AEs are events starting on or after the day of first dose of asfotase alfa and recorded in Study ENB-008-10 (at least 66 months of treatment in Study ENB-008-10).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 2 mg/kg Asfotase Alfa | Dose group shown is as per patient's randomization in Study ENB-006-09. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection site erythema | General disorders | MedDRA 13.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director of Clinical Trials | Alexion Pharmaceuticals, Inc. | 475-230-2596 | ClinicalTrials@alexion.com |
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| ID | Term |
|---|---|
| D007014 | Hypophosphatasia |
| D001847 | Bone Diseases |
| D012279 | Rickets |
| D010018 | Osteomalacia |
| ID | Term |
|---|---|
| D008664 | Metal Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| C570710 | asfotase alfa |
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| Winnipeg |
| Manitoba |
| R3A 1S1 |
| Canada |
| Whyte MP, Madson KL, Phillips D, Reeves AL, McAlister WH, Yakimoski A, Mack KE, Hamilton K, Kagan K, Fujita KP, Thompson DD, Moseley S, Odrljin T, Rockman-Greenberg C. Asfotase alfa therapy for children with hypophosphatasia. JCI Insight. 2016 Jun 16;1(9):e85971. doi: 10.1172/jci.insight.85971. |
| Hypophosphatasia Website for Healthcare Providers | View source |
| HPP support group | View source |
| US Hypophosphatasia Group (Soft Bones) | View source |
| BG002 | Total | Total of all reporting groups |
| Standard Deviation |
| years |
|
| Age, Customized | n % | Count of Participants | Participants |
|
| Sex: Female, Male | n % | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | n % | Count of Participants | Participants |
|
| Race (NIH/OMB) | n % | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants | No |
|
| Hypophosphatasia Phenotype | n % | Count of Participants | Participants |
|
| Age at Onset of Hypophosphatasia Symptoms | Mean | Standard Deviation | Months |
|
| Tanner Stage 1 | n %; Tanner Stage 1 = Prepubertal children | Count of Participants | Participants |
|
| ID | Title | Description |
|---|
| OG000 | Asfotase Alfa Combined | ITT population for Study ENB-008-10, which included all patients that received treatment with asfotase alfa. |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 6 |
| 6 |
| EG001 | 3 mg/kg Asfotase Alfa | Dose group shown is as per patient's randomization in Study ENB-006-09. | 0 | 6 | 0 | 6 | 6 | 6 |
| EG002 | Combined Asfotase Alfa Group | All patients treated with asfotase alfa during Study ENB-008-10 | 0 | 12 | 0 | 12 | 12 | 12 |
| Injection site macule | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Injection site hypertrophy | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Injection site atrophy | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Injection site discolouration | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Injection site pain | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Injection site pruritis | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Discomfort | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Injection site hypersensitivity | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Injection site induration | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Injection site papule | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Injection site reaction | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Injection site swelling | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Enterobiasis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Pharyngitis streptococcal | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Staphylococcal skin infection | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Tinea cruris | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Joint sprain | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Limb injury | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Accidental exposure | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Arthropod sting | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Burns second degree | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Drug administration error | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Joint injury | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Periorbital haematoma | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Post-traumatic pain | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Radius fracture | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Testicular injury | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Epiphyses premature fusion | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Joint hyperextension | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dental discomfort | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Food poisoning | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Tooth crowding | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Conjunctival deposit | Eye disorders | MedDRA 13.0 | Systematic Assessment |
|
| Conjunctivitis | Eye disorders | MedDRA 13.0 | Systematic Assessment |
|
| Conjunctivitis allergic | Eye disorders | MedDRA 13.0 | Systematic Assessment |
|
| Corneal deposits | Eye disorders | MedDRA 13.0 | Systematic Assessment |
|
| Optic atrophy | Eye disorders | MedDRA 13.0 | Systematic Assessment |
|
| Optic disc drusen | Eye disorders | MedDRA 13.0 | Systematic Assessment |
|
| Retinal vascular disorder | Eye disorders | MedDRA 13.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Allergic cough | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Allergic sinusitis | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Ingrowing nail | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Hair colour changes | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Skin discolouration | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 13.0 | Systematic Assessment |
|
| Acute stress disorder | Psychiatric disorders | MedDRA 13.0 | Systematic Assessment |
|
| Attention deficit/hyperactivity disorder | Psychiatric disorders | MedDRA 13.0 | Systematic Assessment |
|
| Initial insomnia | Psychiatric disorders | MedDRA 13.0 | Systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Blood 25-hydroxycholecalciferol decreased | Investigations | MedDRA 13.0 | Systematic Assessment |
|
| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 13.0 | Systematic Assessment |
|
| Haemangioma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 13.0 | Systematic Assessment |
|
| Melanocytic naevus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 13.0 | Systematic Assessment |
|
| Nephrolithiasis | Renal and urinary disorders | MedDRA 13.0 | Systematic Assessment |
|
| Nephrocalcinosis | Renal and urinary disorders | MedDRA 13.0 | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA 13.0 | Systematic Assessment |
|
| Middle ear inflammation | Ear and labyrinth disorders | MedDRA 13.0 | Systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Phimosis | Congenital, familial and genetic disorders | MedDRA 13.0 | Systematic Assessment |
|
| Growth hormone deficiency | Endocrine disorders | MedDRA 13.0 | Systematic Assessment |
|
| Balanitis | Reproductive system and breast disorders | MedDRA 13.0 | Systematic Assessment |
|
| Injection site urticaria | General disorders | MedDRA 13.0 | Systematic Assessment |
|
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| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D009140 | Musculoskeletal Diseases |
| D001851 | Bone Diseases, Metabolic |
| D002128 | Calcium Metabolism Disorders |
| D014808 | Vitamin D Deficiency |
| D001361 | Avitaminosis |
| D003677 | Deficiency Diseases |
| D044342 | Malnutrition |
| D009748 | Nutrition Disorders |