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

• Register: EUCTR
• Last refreshed on: 22 May 2017
• Main ID: EUCTR2017-001831-38-Outside-EU/EEA
• Date of registration: 09/05/2017
• Prospective Registration: Yes
• Primary sponsor: Alexion Pharma GmbH
• 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, and Pharmacokinetics of ENB-0040 (Human Recombinant Tissue-Nonspecific Alkaline Phosphatase Fusion Protein) in Adolescents and Adults with Hypophosphatasia (HPP)
• Target sample size: 19
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001831-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: No treatment Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, United States

Contacts

• Name: European Clinical Trial Information
• Affiliation: Alexion Europe SAS

• Name: European Clinical Trial Information
• Affiliation: Alexion Europe SAS

Key inclusion & exclusion criteria

Inclusion criteria:
Patients must meet all of the following criteria for enrollment 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

Are the trial subjects under 18? yes
Number of subjects for this age range: 6
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 13
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
Patients will be excluded from enrollment 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:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Hypophosphatasia
MedDRA version: 20.0 Level: PT Classification code 10049933 Term: Hypophosphatasia System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Body processes [G] - Genetic Phenomena [G05]

Intervention(s)

Trade Name: Strensiq
Product Name: Asfotase alfa
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ASFOTASE ALFA
Other descriptive name: Human recombinant tissue non-specific alkaline phosphatase fusion protein
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-
INN or Proposed INN: ASFOTASE ALFA
Other descriptive name: Human recombinant tissue non-specific alkaline phosphatase fusion protein
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Efficacy endpoint: Baseline to Week 24
Safety Endpoint: continuous monitoring

Secondary Objective: To evaluate the following:
- Change in bone mineral content (BMC) and bone mineral density (BMD) as measured by dual-energy
X-ray absorptiometry (DEXA)
- Change in walking ability as measured by the Six-Minute Walk Test (6MWT)
- Change in HPP-related osteomalacia as measured by trans-iliac crest bone biopsy

Primary end point(s): - Effect of asfotase alfa on reduction in plasma inorganic pyrophosphate (PPi) and plasma pyridoxal-5' phosphate (PLP)
- Safety and Tolerability of asfotase alfa

Main Objective: To determine the following:
- Effect of asfotase alfa on reduction in plasma inorganic pyrophosphate (PPi) and plasma pyridoxal-5’-phosphate (PLP)
- Tolerability of daily subcutaneous (SC) injections of asfotase alfa

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: For DEXA and 6MWT measures: Every 24 weeks
for osteomalacia measure: Week 24, Week 48

Secondary end point(s): - Change in bone mineral content and density as measured by dual-energy X-ray absorptiometry (DXA)
- Change in walking ability as measured by the Six-Minute Walk Test (6MWT)
- Change in HPP-related osteomalacia as measured by trans-iliac crest bone biopsy

Secondary ID(s)

ENB-009-10

Source(s) of Monetary Support

Alexion Pharma GmbH