Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multi-center, Phase 2, Open-Label Study of Fabrazyme (Recombinant Human a-Galactosidase A) Replacement Therapy in Pediatric Patients With Fabry Disease
Brief Summary: People with Fabry disease have an alteration in their genetic material (DNA) which causes a deficiency of the a-galactosidase A enzyme. This enzyme helps to break down and remove certain types of fatty substances called "glycolipids". These glycolipids are normally present within the body in most cells. In people with Fabry disease, glycolipids build up in various tissues such as the liver, kidney, skin, and blood vessels because a-galactosidase A is not present, or is present in small quantities. The build up of glycolipid levels (also referred to as "globotriaosylceramide" or "GL-3") in these tissues is thought to cause the clinical symptoms that are common to Fabry disease. Symptoms commonly appear during childhood with pain in the hands and feet. This study explored the safety, efficacy and pharmacokinetics of Fabrazyme in pediatric patients aged between 7 and 15 years.


Options:
A: Inclusion Criteria:

* The participant and/or participant's parent(s)/legal guardian(s) must provide written informed assent/consent prior to any protocol-related procedures being performed.
* The participant must had a confirmed diagnosis of Fabry disease as documented by leukocyte α-Galactosidase A (αGAL) activity of \<4 nmol/hr/mg leukocyte (preferred assay; resulted from a central laboratory). If the leukocyte αGAL activity assay was difficult to obtain, the participant might be enrolled based on documented plasma αGAL \<1.5 nmol/hr/mL, with the agreement of the Medical Monitor (resulted from a central laboratory).
* The participant must had evidence of globotriaosylceramide (GL-3) accumulation as documented by plasma GL-3 (\>7.0 µg/mL) or urinary GL-3 (\>0.3 mg GL-3/mmol creatinine) levels (results from a central laboratory).
* The participant must be male ≥5 and ≤18 years of age.

Exclusion Criteria:

* Participant had albuminuria (first morning void urinary albumin/creatinine ratio \>30 mg/g on at least 2 out of 3 consecutive samples, each at least 1 week apart).
* Participant had a Glomerular Filtration Rate (GFR) by iohexol \<90 L/min/1.73m\^2. In case of properly documented low protein intake, values as low as 80 mL/min/1.73 m\^2 might be acceptable, after consultation with the Medical Monitor.
* Participant had documented evidence of stroke or transient ischemic attack (TIA), or if a brain magnetic resonance imaging (MRI) had been performed, bright lesions \>2 mm on T2- or fluid attenuated inversion recovery (FLAIR)- weighted images within the white matter or the basal ganglia.
* Participant had severe and recurrent acroparesthesia, judged by the physician as frequent (more than once a week) pain episodes for at least 3 months that influenced daily activities, irrespective of medication.
* Participant had an end-diastolic left ventricular posterior wall thickness (LVPWTd) and/or an end-diastolic interventricular septum thickness (IVSTd)≥2 standard deviations (SD) compared to normal (based on body surface area \[BSA\] normal ranges from Kampmann, et al 2000) as read at the study site.
* Participant had received prior treatment specific to Fabry Disease.
* Participant had participated in a study employing an investigational drug within 30 days of the start of their participation in this study.
* Participant had any medical condition or extenuating circumstance, which in the opinion of the Study Investigator, could interfere with study compliance.
* Participant had any medical condition or extenuating circumstance, for example diabetes mellitus, which in the opinion of the Study Investigator, could interfere with the interpretation of study results.
* Participant was on treatment with angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs).
* Participant had any contra-indication mentioned in the labeling of Fabrazyme and/or iohexol (Omnipaque).
* Participant or parent(s)/legal guardian(s) was unwilling to comply with the requirements of the protocol.
B: Inclusion Criteria:

* Patients must provide written informed consent
* Patients must be at least 16 years old
* Patients must have a current diagnosis of Fabry disease and have a clinical presentation consistent of Fabry disease (decreased sweating, Fabry pain, angiokeratoma, etc.)
* Patients may not have received enzyme replacement therapy as a treatment for Fabry disease
* Patients must have a documented plasma a-galactosidase A (aGAL) activity of \< 1.5 nmol/hr/mL or a documented leukocyte aGAL activity of \< 4 nmol/hr/mg
* Patients must have one or more of the following: a serum creatinine measurement of 1.2 to 3 mg/dL (106.1 to 265 umol/L) OR estimated creatinine clearance \< 80 mL/min only if the patient's serum creatinine measurement is \< 1.2 mg/dL
* Female patients of childbearing potential must have a negative pregnancy test prior to each dosing and all female patients must use a medically accepted form of contraception

Exclusion Criteria:

* Patient has undergone or is currently scheduled for kidney transplantation or is currently on dialysis
* Patient has acute renal failure
* Patient has participated in a study employing an investigational drug within 30 days of study entry
* Patient has diabetes mellitus or presence of confounding renal disease
* Patient has a history of transient ischemic attack (TIA) or ischemic stroke within 3 months of study entry documented by mild-to-moderate neurological deficit
* Patient has critical coronary disease
* Patient has congestive heart failure
* Patient has severe residual neurological deficit that will confound the detection of new events as determined by an attending neurologist and/or Principal Investigator
* Patient is unwilling to comply with the requirements of the protocol or the patient has a medical condition, serious intercurrent illness, or extenuating circumstances that would significantly decrease study compliance, including prescribed follow-up
C: Inclusion Criteria:

1a. For Cohort 1 (both phases):

- Patients must have completed all study requirements and assessments for Study TKT023 less than 30 (+/-7) days prior to enrolling in Study TKT029 and must have no safety or medical issues that contraindicate participation.

OR

1b. For Cohort 2:

* The patient is between 7 and 17 years of age at the time of informed consent, inclusive.
* The patient must be ERT-naive.
* The patient is a hemizygous male with Fabry disease as confirmed by a deficiency of alpha-galactosidase A activity measured in serum, leukocytes, or fibroblasts. Male patients who do not already have a documented deficiency of alpha-galactosidase A activity will provide a blood sample during screening for determination of alpha-galactosidase A activity level in their serum.

OR

- The patient is a heterozygous female or hemizygous male with Fabry disease as confirmed by a mutation of the alpha-galactosidase A gene. Patients who do not already have a documented mutation of the alpha-galactosidase A gene will provide a blood sample during screening for genotyping.

2. Adequate general health (as determined by the Investigators) to undergo the specified phlebotomy regimen and protocol-related procedures and no safety or medical contraindications for participation.

3. The minor child must assent to participate in the protocol and the parent(s) or legally authorized guardian(s) must have voluntarily signed an Institutional Review Board/Independent Ethics Committee (IRB/IEC) approved informed concent form after all relevant aspects of the study have been explained and discussed with the child and the child's parent(s) or legal guardian(s).

Exclusion Criteria:

Patients who meet any of the following criteria are not eligible for this study:

* Patient and/or the patient's parent(s) or legal guardian(s) are unable to understand the nature, scope, and possible consequences of the study.
* Patient is unable to comply with the protocol, e.g., uncooperative with protocol schedule, refusal to agree to all of the study procedures, inability to return for safety evaluations, or is otherwise unlikely to complete the study, as determined by the Investigator or the medical monitor.
D: Inclusion criteria:

* Patient or legal guardian must provide written informed consent
* Patients must have a clinical diagnosis of Fabry disease and active Fabry disease (clinical signs and symptoms)
* Patients must be at least 7 years of age but no older than 15 years of age at time of enrollment
* Patients must be Tanner Stage ≤ III
* Female patients must have a negative pregnancy test prior to each infusion and use a medically accepted form of contraception throughout the study

Exclusion Criteria:

* Patient has a clinically significant organic disease (with the exception of symptoms relating to Fabry disease) that in the opinion of the investigator would preclude participation in the trial
* Patient has participated in a study employing investigational drug within 30 days of the start of this study
* Patient has received prior treatment with enzyme replacement therapy
* Patient is unable to comply with the clinical protocol

Answer: D