Fabry DiseasePhase 2NCT00084084
Replagal Enzyme Replacement Therapy for Children With Fabry Disease
A Phase 2 study testing Agalsidase alfa in people with Fabry Disease, run by Shire at 14 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 7 to 17 years
- Conditions the study is for
- Fabry Disease
- What is being tested?
- Agalsidase alfa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 14 sitesin 2 countries
- Study dates
- 10 Jun 2004to 15 Jun 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Show all 11Show fewer
- 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).
Who cannot join
- 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.
Trial locations and contacts
14 sites in 2 countries.
14 sites in 2 countries
United States13 sites
Sacred Heart Hospital
Allentown, Pennsylvania, 18102
Clinical Center, National Institutes of Health
Bethesda, Maryland, 20892
Institute of Metabolic Diseases
Dallas, Texas, 75226
Memorial Hospital
Easton, Maryland, 21601
East Tennessee Children's Hospital
Knoxville, Tennessee, 37916
Christus St. Patrick Hospital
Lake Charles, Louisiana, 70601
University of Tennessee, Health Science Center
Memphis, Tennessee, 38163
NYU School of Medicine
New York, New York, 10016
Children's Physician Group
Palm Beach Gardens, Florida, 33410
St. Louis Children's Hospital
St Louis, Missouri, 63110
Office of Michael Cohen
Stafford, Virginia, 22556
Tucson Access Center of Arizona Kidney Disease Hypertension Center
Tucson, Arizona, 85719
University of Arizona Health Sciences Center
Tucson, Arizona, 85724
About this study
Official title: An Open Label Clinical Trial of Replagal Enzyme Replacement Therapy In Children With Fabry Disease Who Have Completed Study TKT023 or Who Are Naive to Enzyme Replacement Therapy
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.
- Conditions
- Fabry Disease
- Being tested
- Agalsidase alfa
- Keywords
- Lysosomes, Storage, Glycolipid, Fabry disease, Stroke, Children, Pediatrics
- Medical subject headings
- Fabry Disease, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Agalsidase alfaDrug
Also called Replagal
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
| Study group | Role | What they receive |
|---|---|---|
| Agalsidase alfa (Cohort 1) | Experimental | Cohort 1: Patients who completed TKT023. Receives: Drug: Agalsidase alfa |
| Agalsidase Alfa (Cohort 2) | Experimental | Cohort 2: Treatment-naive patients. Receives: Drug: Agalsidase alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patients Who Experienced At Least One Adverse Event (AE)
Measured: 362 weeks
Secondary outcomes (8)
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 81
AUC0-∞ is a measure of the total exposure to a drug.
Measured: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 133
AUC0-∞ is a measure of the total exposure to a drug.
Measured: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 159
AUC0-∞ is a measure of the total exposure to a drug.
Measured: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 315/341
AUC0-∞ is a measure of the total exposure to a drug.
Measured: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 81
Cmax is the peak plasma concentration of a drug after administration.
Measured: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 133
Cmax is the peak plasma concentration of a drug after administration.
Measured: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 159
Cmax is the peak plasma concentration of a drug after administration.
Measured: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 315/341
Cmax is the peak plasma concentration of a drug after administration.
Measured: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2004 (estimated)
- Study start10 Jun 2004
- Primary completion15 Jun 2011
- Study completion15 Jun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fabry DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00084084
- Sponsor's protocol ID
- TKT029
- Status last verified
- Jul 2021
- First submitted
- 5 Jun 2004
- Last updated
- 30 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Clinical Trial of Replagal Enzyme Replacement Therapy In Children With Fabry Disease Who Have Completed Study TKT023 or Who Are Naive to Enzyme Replacement Therapy
- ClinicalTrials.gov ID
- NCT00084084
- Acronym / sponsor ID
- TKT029
- Conditions
- Fabry Disease
- Keywords
- Lysosomes, Storage, Glycolipid, Fabry disease, Stroke, Children, Pediatrics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 10 Jun 2004 (actual)
- Primary completion
- 15 Jun 2011 (actual)
- Study completion
- 15 Jun 2011 (actual)
- First posted
- 7 Jun 2004 (estimated)
- Results
- Posted 10 Oct 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Agalsidase alfa (Cohort 1) | Experimental | Drug: Agalsidase alfaCohort 1: Patients who completed TKT023. |
| Agalsidase Alfa (Cohort 2) | Experimental | Drug: Agalsidase alfaCohort 2: Treatment-naive patients. |
Who may qualify
- Ages
- 7 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (11 listed)
- 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
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Agalsidase alfaAlso: Replagal0.2 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 | Drug | Agalsidase Alfa (Cohort 2), Agalsidase alfa (Cohort 1) |
Primary outcome
Patients Who Experienced At Least One Adverse Event (AE)
Time frame: 362 weeks
8 secondary outcomes
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 81
Time frame: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 133
Time frame: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 159
Time frame: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 315/341
Time frame: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 81
Time frame: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 133
Time frame: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 159
Time frame: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 315/341
Time frame: Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25425121Schiffmann 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
14 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Agalsidase alfa in people with Fabry Disease, run by Shire at 14 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Oct 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patients Who Experienced At Least One Adverse Event (AE) (time frame: 362 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00084084, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2021.