This study will evaluate the efficacy and safety of 2.0 mg/kg/week and 2.0 mg/kg/every other week BMN 110 in patients with mucopolysaccharidosis IVA (Morquio A Syndrome). This study will compare the effects of 24 weeks of infusions of BMN 110 at…
ID
Source
Brief title
Condition
- Cytoplasmic disorders congenital
- Inborn errors of metabolism
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of this trial is to evaluate the ability of 2.0 mg/kg/week
BMN 110 and 2.0 mg/kg/qow BMN 110 compared with placebo to enhance endurance in
patients with MPS IVA, as measured by an increase in the number of meters
walked in the 6-minute walk (6MW) test from baseline to Week 24.
Secondary outcome
The secondary objectives of the study are:
* To evaluate the ability of 2.0 mg/kg/week BMN 110 and 2.0 mg/kg/qow BMN 110
compared with placebo to enhance endurance in patients with MPS IVA, as
measured by an increase in the number of stairs climbed per minute in the 3MSC
test from baseline to Week 24.
* To evaluate the ability of 2.0 mg/kg/week BMN 110 and 2.0 mg/kg/qow BMN 110
compared with placebo to reduce urine KS levels in patients with MPS IVA, as
measured by a decrease in urine KS levels from baseline to Week 24.
Background summary
Mucopolysaccharidosis IVA (Morquio A syndrome, MPS IVA) is an inherited
autosomal recessive disorder characterized by deficient activity of
N-acetylgalactosamine-6-sulfatase (GALNS), resulting in macroscopic
accumulation of the glycosaminoglycan (GAG) keratan sulfate (KS) in tissue
macrophages, hyaline cartilage and other connective tissues, heart valve, and
cornea as well as excretion in the urine. This accumulation causes multiple
clinical manifestations including impaired functional capacity, endurance, and
quality of life. There is currently no standard accepted treatment for MPS IVA
other than supportive care. Enzyme replacement therapy (ERT) with BMN 110
(rhGALNS) may be a potential new treatment option for MPS IVA patients. BMN 110
is expected to reduce the progressive accumulation of KS and improve signs and
symptoms of the disease. This study will compare the effects of 24 weeks of
infusions of BMN 110 at doses of 2.0 mg/kg/week and 2.0 mg/kg/every other week
(qow) with placebo in patients with MPS IVA.
Study objective
This study will evaluate the efficacy and safety of 2.0 mg/kg/week and 2.0
mg/kg/every other week BMN 110 in patients with mucopolysaccharidosis IVA
(Morquio A Syndrome). This study will compare the effects of 24 weeks of
infusions of BMN 110 at doses of 2.0 mg/kg/week and 2.0 mg/kg/every other week
(qow) with placebo in patients with MPS IVA.
Study design
This is a Phase 3, randomized, double-blind, placebo-controlled, multinational
study in patients with MPS IVA. Eligible patients will be randomized 1:1:1 to
the 2.0 mg/kg/week BMN 110 group, the 2.0 mg/kg/qow BMN 110 group, or the
placebo control group. All patients will receive weekly double-blind infusions
of 2.0 mg/kg/week BMN 110, 2.0 mg/kg/qow BMN 110 and infusions of placebo on
alternating weeks, or placebo for a total of 24 consecutive weeks. As patients
may experience hypersensitivity reactions associated with the administration of
BMN 110, antihistamine will be administered prior to infusions for all
patients. Pretreatment with an antipyretic may be given at the Investigator*s
discretion. Vital signs will be measured just before, during, and immediately
following the infusion. Adverse events and changes in concomitant medication
will be recorded throughout the study. All patients who participate in this
study will be eligible to receive BMN 110 in an extension study.
Intervention
Patients randomized to active treatment will receive intravenous (IV) infusions
of BMN 110 at a dose of 2.0 mg/kg/week or infusions of BMN 110 at a dose of 2.0
mg/kg/qow. Patients randomized to the 2.0 mg/kg/qow arm will receive infusions
of placebo on alternating weeks. Each infusion will be administered over a
period of approximately 4 hours once a week for 24 consecutive weeks. Patients
randomized to placebo will receive weekly IV infusions of placebo solution at a
volume equivalent to that needed for a 2.0 mg/kg dose of BMN 110. BMN 110 as
well as placebo should be diluted in 0.9% sodium chloride.
Study burden and risks
All of the possible risks from treatment with BMN 110 are unknown. BMN 110 has
been tested in animals and has also been used in a small group of patients with
MPS IVA in another clinical study. The most common side effects seen in the
clinical study so far have been mild or moderate and include cough, fever,
vomiting, headache, and pain in arms or legs.Allergic Reactions: As with any
drug, it is possible that patients could experience an allergic reaction to any
of the drugs or combination of the drugs used in this study. Symptoms of any
allergic reaction can include a rash, hives, itching, and/or difficulty
breathing, closing of the throat, swelling of the lips, tongue or face, and
rarely death. When a X-ray is performed, the patient will be exposed to a small
amount of radiation. Risks associated with drawing blood include: possibility
of discomfort while the blood is being drawn or for a short time afterward,
possibility of bruising or bleeding at the needle puncture site, and rarely,
infection at the needle puncture site. Other possible side effects from blood
draws include lightheadedness and/or fainting. Risks of the physical endurance
tests: The effects of the study drug and some study procedures on a fetus or
baby are unknown. Females who are sexually active and/or are capable of
becoming pregnant must either (a) not have sex or (b) use birth control for 30
days after taking study drug. Like any other experimental drug, this study drug
may have unknown and serious risks that could lead to death. Study procedures
may involve risks or side effects that are not known because of MPS IV A. Also,
things could happen that the doctors don*t know about yet.
105 Digital Drive
Novato, CA 94949
US
105 Digital Drive
Novato, CA 94949
US
Listed location countries
Age
Inclusion criteria
* At least 5 years of age.
* Documented clinical diagnosis of MPS IVA based on clinical signs and symptoms of
MPS IVA and documented reduced fibroblast or leukocyte GALNS enzyme activity
or genetic testing confirming diagnosis of MPS IVA.
* Willing and able to provide written, signed informed consent, or in the case of
patients under the age of 18 (or 16 years, depending on the region), provide written
assent (if required) and written informed consent by a legally authorized
representative after the nature of the study has been explained, and prior to any
research-related procedures.
* Must have an average screening 6MW test distance * 30 and * 325 meters.
* Sexually active patients must be willing to use an acceptable method of contraception
while participating in the study.
* Females of childbearing potential must have a negative pregnancy test at Screening
and be willing to have additional pregnancy tests during the study.
Exclusion criteria
* Previous hematopoietic stem cell transplant (HSCT).
* Previous treatment with BMN 110.
* Has known hypersensitivity to any of the components of BMN 110.
* Major surgery within 3 months prior to study entry or planned major surgery during
the 24-week treatment period.
* Pregnant or breastfeeding at Screening or planning to become pregnant (self or
partner) at any time during the study.
* Use of any investigational product or investigational medical device within 30 days
prior to Screening, or requirement for any investigational agent prior to completion of
all scheduled study assessments.
* Concurrent disease or condition, including but not limited to symptomatic cervical
spine instability, clinically significant spinal cord compression, or severe cardiac
disease that would interfere with study participation or safety as determined by the
Investigator.
* Any condition that, in the view of the Investigator, places the patient at high risk of
poor treatment compliance or of not completing the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010020198-18-NL |
| CCMO | NL34445.018.11 |