Safety and Efficacy Study of Asfotase Alfa in Adolescents and Adults With Hypophosphatasia (HPP)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01163149
• Date of registration: 24/06/2010
• Prospective Registration: No
• Primary sponsor: Alexion Pharmaceuticals
• Public title: Safety and Efficacy Study of Asfotase Alfa in Adolescents and Adults With Hypophosphatasia (HPP)
• Scientific title: A Randomized, Open-Label, Multicenter, Multinational, Dose-Ranging, Concurrent Control Study of the Safety, Efficacy, Pharmacokinetic of ENB-0040 (Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein) in Adolescents and Adults With Hypophosphatasia (HPP)
• Date of first enrolment: June 2010
• Target sample size: 19
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01163149
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Canada, United States

Key inclusion & exclusion criteria

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



Age minimum: 13 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Hypophosphatasia

Intervention(s)

Drug: asfotase alfa

Primary Outcome(s)

Change From Baseline to Week 24 for Plasma Pyridoxal-5' Phosphate (PLP) [Time Frame: Baseline, Week 24]

Change From Baseline to Week 24 for Plasma Inorganic Pyrophosphate (PPi) [Time Frame: Baseline, Week 24]

Safety and Tolerability of Asfotase Alfa [Time Frame: Up to 288 weeks exposure to asfotase alfa]

Secondary Outcome(s)

Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Thickness [Time Frame: Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups).]

Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Volume/Bone Volume [Time Frame: Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups).]

Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA) [Time Frame: Baseline, every 24 weeks through Week 96, then every 48 weeks until Week 288.]

Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) [Time Frame: Baseline, every 24 weeks through Week 96, then every 48 weeks until Week 288.]

Change in Walking Ability as Measured by the Six-Minute Walk Test (6MWT) [Time Frame: Baseline, Week 24 (primary treatment period) and up to 288 weeks of asfotase alfa exposure]

Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Mineralization Lag Time [Time Frame: Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups).]

Secondary ID(s)

ENB-009-10

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 18/09/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01163149