Expanded Access Program for Asfotase Alfa Treatment for Patients With Infantile- or Juvenile-onset Hypophosphatasia (HPP)
Expanded Access Program for Asfotase Alfa Treatment for Patients With Infantile- or Juvenile-onset Hypophosphatasia (HPP)
This clinical trial is being conducted in Hypophosphatasia, a bone disorder caused by gene
 mutation(s) resulting in bone defects. These gene mutations cause low levels of an enzyme
 needed to harden bone. The purpose of this study is to provide access to treatment in a
 disease where no approved treatment exists. This is an experimental treatment provided under
 specific treatment guidelines in which safety endpoints will be collected.
U.S. sites participating in the expanded access program are closed to enrollment.
Inclusion Criteria

 Patients must meet all of the following inclusion criteria for participation in this
 program:

 1. Patient or 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.
 NOTE: Historical results for PLP may be used to determine patient eligibility.
 The criterion for plasma PLP is not applicable if the patient is receiving
 pyridoxine treatment.

 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 spermicide

 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 intra-uterine 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, and a condom for the male partner, since
 at least 14 days prior to Baseline

 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
 postmenopausal or surgically sterile as defined in inclusion criteria 5 above) must
 have a negative urine or serum pregnancy test at Screening.

 Exclusion Criteria

 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.
 Patients who previously received treatment with asfotase alfa may be considered for
 enrollment.