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CompletedNCT00084084Updated Jul 30, 2021Results posted

Replagal Enzyme Replacement Therapy for Children With Fabry Disease

A Phase 2 interventional study of Agalsidase alfa in Fabry Disease, sponsored by Shire. Completed at 14 sites in 2 countries. Open to participants aged 7 Years to 17 Years. Per ClinicalTrials.gov, last updated 2021-07-30.

Sponsored by Shire · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
17
Allocation
Non-randomized
Ages
7 Years to 17 Years
Sex
All
01

Study summary

Primary Objective(s):

  • To assess the safety of Replagal at a dose of 0.2 mg/kg administered over 40 (+/-10) minutes in children with Fabry disease
  • To assess the effect of Replagal on heart rate variability in patients 7 to 17 years of age

Secondary Objective(s):

  • To determine the pharmacokinetics of Replagal at baseline and after the initiation of enzyme replacement therapy (ERT)
  • To determine exploratory measurements of efficacy including renal function (ie, estimated glomerular filtration rate [eGFR] and creatinine clearance), clinical outcomes (in Cohorts 1 and 2), and sweating and left ventricular mass index (LVMI) (Cohort 1, Phase 1 only)
Read the detailed description

TKT029 is an open label multi-center study to assess the safety of enzyme replacement therapy with Replagal (agalsidase alfa) in children with Fabry disease, who have completed 6 months of agalsidase alfa therapy in study TKT023 (Cohort 1) or who are treatment-naïve (Cohort 2) and meet all inclusion/exclusion criteria of this study. The study will consist of every other week treatment with Replagal for 52 weeks, with periodic reassessments by Shire HGT for continuation of the study beyond 52 weeks. A decision on the part of the study sponsor to terminate the study may be made at any time.

In Cohort 1, safety and clinical measurement assessments performed during Week 25 or 26 of Study TKT023 served as the baseline assessments for TKT029. Patients in Cohort 1 began treatment with Replagal manufactured using a roller bottle process (Replagal RB); this portion of treatment is denoted as Cohort 1, Phase 1. Safety evaluation visits for Cohort 1, Phase 1 were to be performed at Weeks 13, 25, 55, and every 26 weeks thereafter until the patient discontinued from the study or transitioned to treatment with Replagal manufactured using a bioreactor process (Replagal AF). The transition to Replagal AF marked the restart of the study clock and was denoted as Cohort 1, Phase 2. Safety evaluation visits for Cohort 1, Phase 2 will be performed at Weeks 1, 13, 25, 55, and every 26 weeks thereafter until the patient discontinues from or the sponsor terminates the study.

Patients in Cohort 2 will receive treatment with Replagal AF only; therefore there is only 1 study phase for these patients. Screening assessments performed at Week -1 will serve as the baseline assessments for this study. Safety evaluation visits for Cohort 2 will be performed at Weeks 13, 25, 37, 55 and every 26 weeks thereafter until the patients discontinues from or the sponsor terminates the study.

The final study visit for both cohorts will follow 30 days after the study study drug infusion, at which time a final safety evaluation will be performed. Patients who complete the study will be interviewed by telephone 30 days after their last study infusion for resolution of any outstanding adverse events (AEs) or concomitant medication changes. Any patient who withdraws early from the study will have a final study visit 30 days after the last study drug infusion, at which time a final safety evaluation will be performed.

02

Conditions studied

  • Fabry Disease

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Keywords

  • Lysosomes
  • Storage
  • Glycolipid
  • Fabry disease
  • Stroke
  • Children
  • Pediatrics
03

In context

Fabry Disease

242 studies on the registry are indexed under Fabry Disease; 54 are open to participants now.

This study's enrollment of 17 is below the median of 22 across 105 interventional studies indexed under Fabry Disease.

Browse Fabry Disease studies →

Lead sponsor

Shire is the lead sponsor of 346 studies on the registry; 2 are open to participants now.

Of its 47 completed or terminated interventional studies of FDA-regulated products, 47 (100%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
7 Years to 17 Years
Sexes eligible
All
Accepts healthy volunteers
No

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.
  1. 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.
  1. 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

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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
17 participants (actual)

Study arms

  • Experimental
    Agalsidase alfa (Cohort 1)

    Cohort 1: Patients who completed TKT023.

    Drug: Agalsidase alfa

  • Experimental
    Agalsidase Alfa (Cohort 2)

    Cohort 2: Treatment-naive patients.

    Drug: Agalsidase alfa

Interventions

  • DrugAgalsidase alfa

    0.2 mg/kg agalsidase alfa administered by IV infusion over 40 (+/- 10) minutes every other week for 52 weeks, with periodic reassessments for study continuation beyond 52 weeks

    Also known as: Replagal

06

What researchers measure

Primary outcomes

  1. Patients Who Experienced At Least One Adverse Event (AE)

    Time frame: 362 weeks

Secondary outcomes

  1. Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 81

    AUC0-∞ is a measure of the total exposure to a drug.

    Time frame: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.

  2. Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 133

    AUC0-∞ is a measure of the total exposure to a drug.

    Time frame: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.

  3. Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 159

    AUC0-∞ is a measure of the total exposure to a drug.

    Time frame: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.

  4. Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 315/341

    AUC0-∞ is a measure of the total exposure to a drug.

    Time frame: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.

  5. Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 81

    Cmax is the peak plasma concentration of a drug after administration.

    Time frame: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.

  6. Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 133

    Cmax is the peak plasma concentration of a drug after administration.

    Time frame: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.

  7. Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 159

    Cmax is the peak plasma concentration of a drug after administration.

    Time frame: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.

  8. Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 315/341

    Cmax is the peak plasma concentration of a drug after administration.

    Time frame: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.

Other outcomes

  1. Heart Rate Variability - Change From Baseline at Week 185 in SDNN

    Heart rate variability was assessed by 2-hour Holter monitoring. Standard deviation of all filtered RR intervals over the length of the analysis (SDNN) was measured.

    Time frame: Week 185

07

Results

Posted Oct 10, 2013

Participant flow

Phase 1 (Treatment With Replagal RB)
Participant flow — Phase 1 (Treatment With Replagal RB)
MilestoneAgalsidase Alfa (Cohort 1)
Started17
Completed16
Not completed1
Withdrew: Lost to follow-up1
Phase 2 (Transition to Replagal AF)
Participant flow — Phase 2 (Transition to Replagal AF)
MilestoneAgalsidase Alfa (Cohort 1)
Started11
Completed10
Not completed1
Withdrew: Failure to visit clinic as scheduled1

Outcome measures

PrimaryPatients Who Experienced At Least One Adverse Event (AE)
Time frame:
362 weeks
Reported as:
Number · participants
Patients Who Experienced At Least One Adverse Event (AE)
participantsAgalsidase Alfa (Cohort 1)
Patients Who Experienced At Least One Adverse Event (AE)17
SecondaryPharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 81

AUC0-∞ is a measure of the total exposure to a drug.

Time frame:
Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Reported as:
Mean · min·U/mL
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 81
min·U/mLAgalsidase Alfa (Cohort 1)
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 81245282 ± 159071
SecondaryPharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 133

AUC0-∞ is a measure of the total exposure to a drug.

Time frame:
Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Reported as:
Mean · min·U/mL
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 133
min·U/mLAgalsidase Alfa (Cohort 1)
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 133295779 ± 161058
SecondaryPharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 159

AUC0-∞ is a measure of the total exposure to a drug.

Time frame:
Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Reported as:
Mean · min·U/mL
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 159
min·U/mLAgalsidase Alfa (Cohort 1)
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 159218078 ± 73560
SecondaryPharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 315/341

AUC0-∞ is a measure of the total exposure to a drug.

Time frame:
Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Reported as:
Mean · min·U/mL
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 315/341
min·U/mLAgalsidase Alfa (Cohort 1)
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 315/341213193 ± 119581
Other pre-specifiedHeart Rate Variability - Change From Baseline at Week 185 in SDNN

Heart rate variability was assessed by 2-hour Holter monitoring. Standard deviation of all filtered RR intervals over the length of the analysis (SDNN) was measured.

Time frame:
Week 185
Reported as:
Mean · msec
Heart Rate Variability - Change From Baseline at Week 185 in SDNN
msecAgalsidase Alfa (Cohort 1)
Heart Rate Variability - Change From Baseline at Week 185 in SDNN20.256 ± 29.060
SecondaryPharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 81

Cmax is the peak plasma concentration of a drug after administration.

Time frame:
Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Reported as:
Mean · U/mL
Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 81
U/mLAgalsidase Alfa (Cohort 1)
Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 813173 ± 969
SecondaryPharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 133

Cmax is the peak plasma concentration of a drug after administration.

Time frame:
Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Reported as:
Mean · U/mL
Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 133
U/mLAgalsidase Alfa (Cohort 1)
Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 1333842 ± 1235
SecondaryPharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 159

Cmax is the peak plasma concentration of a drug after administration.

Time frame:
Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Reported as:
Mean · U/mL
Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 159
U/mLAgalsidase Alfa (Cohort 1)
Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 1593842 ± 1235
SecondaryPharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 315/341

Cmax is the peak plasma concentration of a drug after administration.

Time frame:
Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Reported as:
Mean · U/mL
Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 315/341
U/mLAgalsidase Alfa (Cohort 1)
Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 315/3413568 ± 1492

Adverse events

Collected over 362 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Safety Population RB—2/17 (11.8%)17/17 (100%)
Transition Safety Population—2/11 (18.2%)11/11 (100%)
Most frequent serious events
Most frequent serious events
EventSafety Population RBTransition Safety Population
Cerebrovascular AccidentNervous system disorders1/171/11
Vertigo PositionalEar and labyrinth disorders1/171/11
Facial Bones FractureInjury, poisoning and procedural complications1/171/11
Renal InjuryInjury, poisoning and procedural complications1/171/11
Road Traffic AccidentInjury, poisoning and procedural complications1/171/11
Traumatic Liver InjuryInjury, poisoning and procedural complications1/171/11
Pectus ExcavatumCongenital, familial and genetic disorders0/171/11
DehydrationMetabolism and nutrition disorders1/170/11
NeuralgiaNervous system disorders1/170/11
Most frequent other events
Showing 10 of 209
Most frequent other events
EventSafety Population RBTransition Safety Population
CoughRespiratory, thoracic and mediastinal disorders13/1710/11
PyrexiaGeneral disorders12/179/11
Abdominal PainGastrointestinal disorders8/178/11
Pain in ExtremityMusculoskeletal and connective tissue disorders8/178/11
HeadacheNervous system disorders9/177/11
NeuralgiaNervous system disorders9/177/11
Chest PainGeneral disorders6/177/11
Nasal CongestionRespiratory, thoracic and mediastinal disorders10/176/11
NasopharyngitisInfections and infestations7/176/11
DyspnoeaRespiratory, thoracic and mediastinal disorders3/176/11

Baseline characteristics

Age, Continuous
Age, Continuous(years)Agalsidase Alfa (Cohort 1)
Mean11.99 ± 3.2464
Sex: Female, Male
Sex: Female, Male(Participants)Agalsidase Alfa (Cohort 1)
Female1
Male16
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Agalsidase Alfa (Cohort 1)
White15
Hispanic2
Baseline Heart Rate Variability (SDNN)
Baseline Heart Rate Variability (SDNN)(msec)Agalsidase Alfa (Cohort 1)
Mean98.947 ± 32.324
08

Study locations

14 sites
  • Tucson Access Center of Arizona Kidney Disease Hypertension Center
    Tucson, Arizona 85719, United States
  • University of Arizona Health Sciences Center
    Tucson, Arizona 85724, United States
  • Children's Physician Group
    Palm Beach Gardens, Florida 33410, United States
  • Christus St. Patrick Hospital
    Lake Charles, Louisiana 70601, United States
  • Clinical Center, National Institutes of Health
    Bethesda, Maryland 20892, United States
  • Memorial Hospital
    Easton, Maryland 21601, United States
  • St. Louis Children's Hospital
    Saint Louis, Missouri 63110, United States
  • NYU School of Medicine
    New York, New York 10016, United States
  • Sacred Heart Hospital
    Allentown, Pennsylvania 18102, United States
  • East Tennessee Children's Hospital
    Knoxville, Tennessee 37916, United States
  • University of Tennessee, Health Science Center
    Memphis, Tennessee 38163, United States
  • Institute of Metabolic Diseases
    Dallas, Texas 75226, United States
  • Office of Michael Cohen
    Stafford, Virginia 22556, United States
  • The Hospital for Sick Children
    Toronto, Ontario M5G 1X8, Canada
09

References and documents

Publications

  • Schiffmann R, Pastores GM, Lien YH, Castaneda V, Chang P, Martin R, Wijatyk A. Agalsidase alfa in pediatric patients with Fabry disease: a 6.5-year open-label follow-up study. Orphanet J Rare Dis. 2014 Nov 26;9:169. doi: 10.1186/s13023-014-0169-6. PubMed 25425121 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 30, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00084084
Lead sponsor
Shire
Responsible party
Sponsor
First posted
Jun 7, 2004
Start date
Jun 10, 2004
Primary completion
Jun 15, 2011
Completion
Jun 15, 2011
Results posted
Oct 10, 2013
Last update
Jul 30, 2021

Study contacts

Study Director
study director · Takeda

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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