Access Program for Asfotase Alfa
- Conditions
- HypophosphatasiaMedDRA version: 18.0Level: PTClassification code 10049933Term: HypophosphatasiaSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Body processes [G] - Genetic Phenomena [G05]
- Registration Number
- EUCTR2015-000809-39-FR
- Lead Sponsor
- Alexion Pharma International Sàrl
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 100
Patients must meet all of the following inclusion criteria to be eligible for participation in this program:
1.Parent or legal guardian must provide written informed consent prior to the performance of any program-related procedures and must be willing to comply with program procedures. Where appropriate and required by local regulations, patient assent for participation must also be obtained.
2.Patient must have a documented diagnosis of HPP as indicated by a documented history of HPP-related skeletal abnormalities and one or more of the following:
• Documented tissue-nonspecific alkaline phosphatase (TNSALP) gene mutation(s)
• Serum alkaline phosphatase (ALP) level below the age-adjusted normal range AND plasma pyridoxal-5’-phosphate (PLP) above the upper limit of normal at Screening.
3.Patient must have infantile- or juvenile-onset HPP, defined as documented onset of signs/symptoms of HPP prior to 18 years of age.
4.Male patient is:
• Prepubertal; OR
• Surgically sterile (defined as vasectomized for =6 months at Baseline); OR
• Non-surgically sterile (defined as non-vasectomized or vasectomized for <6 months at Baseline) and his female spouse/partner who is of childbearing potential must be using highly effective contraception consisting of two forms of birth control (at least one of which must be a barrier method) as described below starting at Baseline and continuing for 3 months after program completion.
- Simultaneous use of condom, and for the female partner established use of hormonal contraceptives (eg, oral, injected, implanted) or intra-uterine contraceptive device
- Simultaneous use of condom, and for the female partner occlusive cap (diaphragm or cervical/vault caps) with intravaginally applied spermicide5.Patient must have infantile- or juvenile-onset HPP, defined as documented onset of signs/symptoms of HPP prior to 18 years of age.
5.Female patient is:
• Of non-childbearing potential, defined as:
- Prepubertal; OR
- Post-menopausal (defined as absence of menses for 12 months prior to Baseline or bilateral oophorectomy or hysterectomy with bilateral oophorectomy at least 6 months prior to Baseline); OR
- Surgically sterile (defined as having hysterectomy or tubal ligation at least 6 months prior to Baseline)
OR
• Of childbearing potential, and:
- Not sexually active; OR
- Sexually active with non-sterile male spouse/partner (sterile male spouse/partner defined as a man vasectomized for =6 months) and must be using highly effective contraception consisting of two forms of birth control (at least one of which must be a barrier method) as described below and continuing for 3 months after program completion.
- Simultaneous use of hormonal contraceptives (eg, oral, injected, implanted) or intrauterine contraceptive device since at least 4 weeks prior to Baseline, and condom for the male partner
- Simultaneous use of occlusive cap (diaphragm or cervical/vault caps) with
intravaginally applied spermicide,
6. Male patients who are pubertal or post-pubertal and not surgically sterile (surgically sterile defined as vasectomized for =6 months) must agree to not donate sperm during program participation and for 3 months after program completion.
7.Female patients of childbearing potential (ie, those who are not prepubertal or post-menopausal or surgically sterile as defined in inclusion criteria 5 above) must have a negative urine or serum pregnancy test at Screening.
Are the trial subjects under
Patients will be excluded from participation in this program if they meet one or more of the following exclusion criteria:
1.Patient has geographic access to and qualifies for enrollment (as determined by the Sponsor and Investigator) in any other Alexion-sponsored clinical trials of asfotase alfa that are open to enrollment (eg, ENB-010-10).
2.Patient is pregnant, trying to become pregnant, or is lactating.
3.Patient has a documented sensitivity to any of the components of asfotase alfa.
4.Patient has serum calcium and/or phosphorus levels below the normal range at Screening.
5.Patient is currently enrolled in any other program or study involving an investigational new drug, device, or treatment for HPP (eg, bone marrow transplantation).
6.Patient has any other medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the investigator, may significantly interfere with program compliance, including all evaluations and follow-up activities.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the safety and tolerability of subcutaneous (SC) injections of asfotase alfa administered 6 times weekly (at a dose of 1 mg/kg) or 3 times weekly (at a dose of 2 mg/kg) at the discretion of the Investigator.;Secondary Objective: To evaluate the effect of asfotase alfa on:<br>1.Physical function<br>2.Change in assistive device use for ambulation<br>3.Growth as measured by change in height and weight Z-scores<br>4.Change in the skeletal manifestations of HPP as measured by skeletal radiographs<br>5.Overall survival<br>6.Respiratory support as measured by respiratory support status<br>;Primary end point(s): To assess the safety and tolerability of subcutaneous (SC) injections of asfotase alfa administered 6 times weekly (at a dose of 1 mg/kg) or 3 times weekly (at a dose of 2 mg/kg);Timepoint(s) of evaluation of this end point: Study duration
- Secondary Outcome Measures
Name Time Method Secondary end point(s): evaluation of the effect of asfotase alfa on:<br>1.Physical function<br>2.Change in assistive device use for ambulation<br>3.Growth as measured by change in height and weight Z-scores<br>4.Change in the skeletal manifestations of HPP as measured by skeletal radiographs<br>5.Overall survival<br>6.Respiratory support as measured by respiratory support status<br>;Timepoint(s) of evaluation of this end point: Physical function, Respiratory support status and Physical examination (including length/height and weight) : at screening, day 1, week 4, week 12, week 24, every 6 months and EOP<br>Ambulatory assistive devices assessments: day 1, week 12, week 24, every 6 months and EOP<br>Skeletal radiographs: Day1, performed as part of standard of care and as clincally indicated<br>Overall survival : study duration