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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01163149
Other study ID # ENB-009-10
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date June 2010
Est. completion date June 2016

Study information

Verified date March 2019
Source Alexion Pharmaceuticals
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This clinical trial was conducted to study hypophosphatasia (HPP), a bone disorder caused by gene mutations or changes. These gene mutations cause low levels of an enzyme needed to harden bone. The purpose of this study was to test the safety and efficacy of two doses of the study drug called asfotase alfa as compared to a control group to see effects on adolescents and adults with HPP.


Description:

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.


Recruitment information / eligibility

Status Completed
Enrollment 19
Est. completion date June 2016
Est. primary completion date June 2016
Accepts healthy volunteers No
Gender All
Age group 13 Years to 65 Years
Eligibility Inclusion criteria:

Patients must meet all of the following inclusion criteria to be eligible for participation in this study:

- Patients or their legal representative(s) must provide written informed consent prior to undergoing any study-related procedures

- Patients must be = 13 and = 65 years of age at the time of study enrollment

- Female patients of childbearing potential and sexually mature males must agree to use a medically acceptable form of birth control; for the purposes of this study, females are considered of non-childbearing potential if they are surgically sterile (i.e., have undergone a total hysterectomy, bilateral salpingo-oophorectomy or tubal ligation) or are post-menopausal, defined as having complete cessation of menstruation for at least 1 year after 45 years of age

- Patients must have a pre-established clinical diagnosis of HPP as indicated by:

- Serum alkaline phosphatase (ALP) below the age-adjusted normal range

- Plasma PLP at least twice the upper limit of normal (no vitamin B6 administered for at least 1 week prior to determination)

- Evidence of osteopenia or osteomalacia on skeletal radiographs

- Patients must have osteomalacia on bone biopsy, characterized by an MLT z-score of +2 or more (results from ENB-001-08 may be used)

- Patients must be willing to comply with study procedures and the visit schedule

Exclusion criteria:

Patients will be excluded from participation in this study if they meet any of the following exclusion criteria:

- Women who are pregnant or lactating

- History of sensitivity to tetracycline

- Serum calcium or phosphate levels below the normal range

- Serum 25(OH) vitamin D below 20 ng/mL

- Serum creatinine or parathyroid hormone (PTH) levels above the upper limit of normal

- Medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities

- Orthopedic surgery within 12 months prior to study entry that may interfere with the ability to perform functional assessments for the study

- Prior treatment with bisphosphonates within 2 years of study entry for any length of time or for more than 2 years at any time point; for patients with prior bisphosphonate use that is allowed, the bone resorption markers serum C-telopeptide and urine N-telopeptide or urine deoxypyridinoline must also be within the normal range or elevated to be eligible for study participation

- Treatment with PTH within 6 months prior to the start of asfotase alfa administration

- Participation in an interventional or investigational drug study within 30 days prior to study participation

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
asfotase alfa
Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (total of 2.1 mg/kg/week)
asfotase alfa
Cohort 2: Daily SC injections of 0.5 mg/kg Asfotase Alfa (3.5 mg/kg/week total)

Locations

Country Name City State
Canada Health Sciences Centre Winnipeg, University of Manitoba Winnipeg Manitoba
United States Duke University Medical Center Durham North Carolina
United States Shriner's Hospital for Children Saint Louis Missouri

Sponsors (1)

Lead Sponsor Collaborator
Alexion Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

Millán JL, Narisawa S, Lemire I, Loisel TP, Boileau G, Leonard P, Gramatikova S, Terkeltaub R, Camacho NP, McKee MD, Crine P, Whyte MP. Enzyme replacement therapy for murine hypophosphatasia. J Bone Miner Res. 2008 Jun;23(6):777-87. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Change From Baseline to Week 24 for Plasma Pyridoxal-5' Phosphate (PLP) Blood samples were collected to evaluate the effect of asfotase alfa on reduction in plasma pyridoxal-5' phosphate (PLP) Baseline, Week 24
Primary Change From Baseline to Week 24 for Plasma Inorganic Pyrophosphate (PPi) Blood samples were collected to evaluate the effect of asfotase alfa on reduction in plasma inorganic pyrophosphate (PPi) Baseline, Week 24
Primary Safety and Tolerability of Asfotase Alfa The safety and tolerability of daily subcutaneous (SC) injections of asfotase alfa was assessed by routine monitoring of patients for treatment-emergent adverse events (TEAEs) and injection-associated reactions (IARs). Up to 288 weeks exposure to asfotase alfa
Secondary Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) A DXA scan was performed to evaluate bone mineral content (BMC) of the spine, hip, and whole body during the primary (first 24 weeks) and extension treatment periods (up to 288 weeks). Baseline, every 24 weeks through Week 96, then every 48 weeks until Week 288.
Secondary Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) A DXA scan was performed to evaluate bone bone mineral density (BMD) of the spine, hip, and whole body during the primary (first 24 weeks) and extension treatment periods (up to 288 weeks). Baseline, every 24 weeks through Week 96, then every 48 weeks until Week 288.
Secondary Change in Walking Ability as Measured by the Six-Minute Walk Test (6MWT) The patient was instructed to walk the length of a pre-measured hallway for 6 minutes. The primary measurement was distance walked (in meters). Baseline, Week 24 (primary treatment period) and up to 288 weeks of asfotase alfa exposure
Secondary Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Volume/Bone Volume A trans-iliac crest bone biopsy was performed to quantify changes from Baseline in histomorphometric parameters relevant for evaluation of osteomalacia severity, including Osteoid Volume/Bone Volume (%). The difference in time under observation between asfotase alfa groups (Week 48) and control group (Week 24) resulted from study design, ie, control subjects transitioned to active treatment after the Week 24 visit. Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups).
Secondary Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Thickness A trans-iliac crest bone biopsy was performed to quantify changes from Baseline in histomorphometric parameters relevant for evaluation of osteomalacia severity, including Osteoid Thickness (um). The difference in time under observation between asfotase alfa groups (Week 48) and control group (Week 24) resulted from study design, ie, control subjects transitioned to active treatment after the Week 24 visit. Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups).
Secondary Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Mineralization Lag Time A trans-iliac crest bone biopsy was performed to quantify changes from Baseline in histomorphometric parameters relevant for evaluation of osteomalacia severity, including Mineralization Lag Time (days). The difference in time under observation between asfotase alfa groups (Week 48) and control group (Week 24) resulted from study design, ie, control subjects transitioned to active treatment after the Week 24 visit. Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups).
See also
  Status Clinical Trial Phase
Completed NCT03418389 - Evaluate and Monitor Physical Performance of Adults Treated With Asfotase Alfa for Hypophosphatasia
Recruiting NCT02237625 - Natural History Study of Patients With Hypophosphatasia (HPP)
Completed NCT02291497 - Burden of Disease in Hypophosphatasia (HPP) N/A
Enrolling by invitation NCT03655223 - Early Check: Expanded Screening in Newborns
Active, not recruiting NCT04195763 - Patient Reported Outcomes in Adults With Pediatric-onset Hypophosphatasia Treated With Strensiq® (Asfotase Alfa)
Not yet recruiting NCT05596539 - Prospective, Longitudinal, Observational Registry of Adult Patients With Hypophosphatasia (REG-HYPO)
Completed NCT02796885 - Characterisation of Adult-Onset Hypophosphatasia
Completed NCT02751801 - Health Burden of Hypophosphatasia
Completed NCT05890794 - Pilot Trial of Single Dose Ilofotase Alfa in Hypophosphatasia Phase 1/Phase 2
Recruiting NCT06079359 - Phase 3 Study of ALXN1850 in Treatment-Naïve Pediatric Participants With HPP Phase 3
Recruiting NCT05234567 - A Prospective Sub-Study of the Global Hypophosphatasia Registry
Completed NCT02797821 - Pharmacokinetic and Dose Response Study of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia (HPP) Phase 2
Completed NCT04925804 - Unraveling Genetics of HypoPhosPhatasia (HPP Genetics)
Completed NCT02531867 - Post-approval Clinical Study of Asfotase Alfa Treatment for Patients With Hypophosphatasia (HPP) in Japan Phase 4
Completed NCT01406977 - Dose Escalation Study to Evaluate the Safety and Tolerability of Multiple Infusions of BPS804 in Adults With Hypophosphatasia (HPP) Phase 2
Recruiting NCT01793168 - Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Completed NCT01176266 - Open-Label Study of Asfotase Alfa in Infants and Children ≤ 5 Years of Age With Hypophosphatasia (HPP) Phase 2/Phase 3
Withdrawn NCT00894075 - Safety and Efficacy Study of ENB-0040 in Juvenile Patients With Hypophosphatasia (HPP) Phase 2
Active, not recruiting NCT04222452 - The PORTRAIT Study
Recruiting NCT06079281 - Phase 3 Study of ALXN1850 Versus Placebo in Adolescent and Adult Participants With HPP Who Have Not Previously Been Treated With Asfotase Alfa Phase 3