A Study of Replagal in Treatment-naïve Adults With Fabry Disease

June 14, 2024 updated by: Shire

A Phase 3, Open-label Study to Evaluate the Efficacy and Safety of REPLAGAL® in Treatment-naïve Subjects With Fabry Disease

In this study, adults with Fabry Disease who have not had any treatment for this condition will be treated with Replagal. The main aim of the study is to check if Replagal improves kidney function and heart structure of participants with Fabry Disease. Participants will receive one Replagal infusion every other week for up to 104 weeks. They will visit the clinic every 12 to 14 weeks during treatment with a follow-up visit 2 weeks after treatment.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
17

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Canada
      • Calgary, Canada, AB T2E 7Z4
        • M.A.G.I.C. Clinic Ltd. Metabolics and Genetics in Calgary
      • Halifax, Canada, B3H 1V7
        • Queen Elizabeth II Health Sciences Center
  • Finland
      • Turku, Finland, FI-20521
        • Turun yliopistollinen keskussairaala
      • Vaasa, Finland, 65130
        • Vaasan Keskussairaala
  • Germany
      • Berlin, Germany, 10117
        • Charité - Universitätsklinikum
      • Hochheim, Germany, 65239
        • SphinCS
      • Mainz, Germany, 55131
        • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
      • Müllheim, Germany, 79379
        • Fachinternistische Gemeinschaftspraxis
      • Wuerzburg, Germany, 97080
        • Universitaetsklinikum Wuerzburg
  • Greece
      • Athens, Greece, 12462
        • Attikon University General Hospital
      • Athens, Greece, 11527
        • Laiko General Hospital of Athens
      • Heraklion, Greece, 71500
        • University General Hospital of Heraklion
      • Ioannina, Greece, 45500
        • University Hospital of Ioannina
      • Kallithea, Greece, 17674
        • Onasseio Private Practise Hospital of Piraeus
      • Thessaloniki, Greece, 54645
        • Papageorgiou General Hospital of Thessaloniki
  • Poland
      • Krakow, Poland, 30-033
        • Szpital Uniwersytecki
      • Warszawa, Poland, 04-628
        • Narodowy Instytut Kardiologii im Prymasa Tysiaclecia Kardynala Stefana Wyszynskiego - Instytut Badaw
      • Wroclaw, Poland, 50-556
        • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
  • Portugal
      • Coimbra, Portugal, 3000-459
        • Centro Hospitalar E Universitario de Coimbra EPE
      • Guimaraes, Portugal, 4835-044
        • Hospital Senhora da Oliveira - Guimaraes, E.P.E
      • Lisboa, Portugal, 1649-035
        • Centro Hospitalar Lisboa Norte, E.P.E. - Hospital de Santa Maria
  • Spain
      • Alicante, Spain, 3010
        • Hospital General Universitario de Alicante
      • Almeria, Spain, 4009
        • Hospital de Torrecardenas
      • Barcelona, Spain, 8035
        • Hospital Universitario Vall d'Hebron - PPDS
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio - PPDS
      • Zaragoza, Spain, 50012
        • Hospital Quironsalud Zaragoza
  • Sweden
      • Uppsala, Sweden, 75185
        • Akademiska Sjukhuset i Uppsala

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • The participant must voluntarily sign an Institutional Review Board (IRB)/Independent Ethics Committee/Research Ethics Board approved informed consent form after all relevant aspects of the study have been explained and discussed with the participant.

  • The participant has Fabry disease as confirmed at screening by the following criteria using a dried blood spot (DBS) assay:

    1. For male participants, Fabry disease is confirmed by a deficiency of alpha-galactosidase A (GLA) activity and a mutation in the GLA gene
    2. For female participants, Fabry disease is confirmed by a mutation in the GLA gene
  • The participant is 18 to 65 years of age, inclusive.
  • Female participants must have a negative pregnancy test at screening.
  • Female participants of child-bearing potential must agree to use a medically acceptable method of contraception at all times during the study and for at least 14 days after the final study infusion; the methods of acceptable contraception are listed in the protocol.
  • The participant is deemed, as determined by the investigator, to have adequate general health to undergo the specified protocol-related procedures and to have no safety or medical contraindications for participation.
  • The participant has not received any treatment (approved or investigational) specific to Fabry disease, such as enzyme replacement therapy (ERT), chaperone therapy, or substrate reduction therapy.
  • The participant must have an eGFR of 45 to 120 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2); eGFR will be calculated by a Shire-designated laboratory using the CKD-EPI formula. If the eGFR measurement at screening is not within the range, a second eGFR measurement may be completed and, if in range, used as the screening value. If a second measurement is taken, a minimum of 1 week and maximum of 30 days should separate it from the first. This inclusion criterion follows the European Guidelines for Treatment of Fabry Disease and Kidney Disease Improving Global Outcomes guidelines for classification of renal disease.
  • The participant has left ventricular hypertrophy (LVH), where LVH is defined as left ventricular mass index (LVMI) greater than (>) 50 gram per square meter (g/m^2.7) confirmed by cardiac magnetic resonance imaging (cMRI) at screening. The cMRI value at screening will serve as the baseline value.

Exclusion Criteria:

  • In the opinion of the investigator, the participant's life expectancy is less than or equal to (<=) 5 years.
  • The participant has undergone or is scheduled to undergo kidney transplantation or is currently on dialysis, or has any signs or symptoms of end stage renal disease.
  • Urine protein/creatinine ratio (PCR) greater than (>) 1.5 milligram per milligram (mg/mg).
  • Participants who have clinically relevant history of allergy or signs or symptoms of severe hypersensitivity, (including hypersensitivity to the REPLAGAL active substance or any of the excipients), which in the investigator's judgment, will substantially increase the participant's risk if he or she participates in the study.
  • Cardiac fibrosis involving more than 2 segments, as determined by cMRI at screening.
  • In the opinion of the investigator, the participant has non-Fabry disease-related cause of end-organ (renal, cardiac, central nervous system) dysfunction/failure or is receiving medications that may affect the rate of disease progression, as assessed by cardiac and/or renal measures.
  • The participant has a positive test at screening for hepatitis B surface antigen, positive test for hepatitis B core antibody, positive test for hepatitis C (HCV) antibody with confirmation by HCV-ribonucleic acid polymerase chain reaction testing, or positive test for human immunodeficiency virus antibody.
  • Treatment with REPLAGAL at any time prior to the study.

  • Prior treatment with any of the following medications:

    1. FABRAZYME (agalsidase beta) and its biosimilars
    2. GLYSET (miglitol)
    3. ZAVESCA (miglustat)
    4. CERDELGA (eliglustat)
    5. GALAFOLD (migalastat)
    6. Any investigational product for treatment of Fabry disease

  • Treatment at any time during the study with the following medications:

    1. Chloroquine
    2. Amiodarone
    3. Monobenzone
    4. Gentamicin
  • The participant is pregnant or lactating.
  • The participant has a body mass index > 39 kilogram per square meter (kg/ m^2). (Body mass index [BMI] = kg/ m^2).
  • The participant is treated or has been treated with any investigational drug within 30 days of study start.
  • The participant is unable to understand the nature, scope, and possible consequences of the study.
  • The participant is unable to comply with the protocol, eg, uncooperative with protocol schedule, refusal to agree to all of the study procedures, inability to return for evaluations, or is otherwise unlikely to complete the study, as determined by the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: REPLAGAL
Participants will receive REPLAGAL 0.2 milligram per kilogram (mg/kg) body weight of intravenous (IV) infusion Every Other Week (EOW) for 104 weeks.
Drug: REPLAGAL
Participants will receive REPLAGAL 0.2 mg/kg body weight of IV infusion for 104 weeks.
Other Names:
  • SHP675

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Renal Function at Week 104
Time Frame: Baseline, Week 104
Renal function was planned to be assessed by estimated glomerular filtration rate (eGFR) using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. The eGFR was planned to be calculated by CKD-EPI formula: eGFR = 141 x min (Serum Creatinine [Scr]/κ,1)^(α) x max(Scr/κ,1)^(-1.209) x 0.993^(Age) x 1.018 (if female) x 1.159 (if black) where: Scr was serum creatinine (mg/dL); κ was 0.7 for females and 0.9 for males; α was -0.329 for females and -0.411 for males; min indicated the minimum of Scr/κ or 1; max indicated the maximum of Scr /κ or 1. Change from baseline in renal function at Week 104 was planned to be reported.
Baseline, Week 104
Change From Baseline in Cardiac Structure at Week 104
Time Frame: Baseline, Week 104
Cardiac structure was planned to be assessed by left ventricular mass index (LVMI) using cardiac magnetic resonance imaging (cMRI). Change from baseline in cardiac structure at Week 104 was planned to be reported.
Baseline, Week 104

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Annualized Rate of Change in Estimated Glomerular Filtration Rate (eGFR) up to Week 104
Time Frame: From Baseline up to Week 104
Annualized rate of change in eGFR up to Week 104 was planned to be reported.
From Baseline up to Week 104
Annualized Rate of Change in Left Ventricular Mass Index (LVMI) up to Week 104
Time Frame: From Baseline up to Week 104
Annualized rate of change in LVMI up to Week 104 was planned to be reported.
From Baseline up to Week 104
Change From Baseline in eGFR up to Week 104
Time Frame: From Baseline up to Week 104
Change from baseline in eGFR up to Week 104 was planned to be reported.
From Baseline up to Week 104
Change From Baseline in LVMI up to Week 104
Time Frame: From Baseline up to Week 104
Change from baseline in LVMI up to Week 104 was planned to be reported.
From Baseline up to Week 104
Change From Baseline in Proteinuria up to Week 104
Time Frame: From Baseline up to Week 104
Proteinuria was to be measured based on protein/creatinine ratio (PCR). Change from baseline in proteinuria up to Week 104 was planned to be reported.
From Baseline up to Week 104
Change From Baseline in Cardiac Fibrotic Segments up to Week 104
Time Frame: From Baseline up to Week 104
Change from baseline in cardiac fibrotic segments suggestive of cardiac fibrosis up to Week 104 was planned to be assessed by volume of fibrosis, measured by cMRI.
From Baseline up to Week 104
Change From Baseline in Interventricular Septal End-Diastolic Thickness and Posterior Wall Thickness in Diastole up to Week 104
Time Frame: From Baseline up to Week 104
Change from baseline in interventricular septal end-diastolic thickness and posterior wall thickness in diastole up to Week 104 was planned to be measured by cMRI.
From Baseline up to Week 104
Change From Baseline in Plasma Globotriaosylsphingosine (Lyso-Gb3) up to Week 104
Time Frame: From Baseline up to Week 104
Change from baseline in lyso-Gb3 up to Week 104 was planned to be reported.
From Baseline up to Week 104
Number of Participants With Adverse Events (AEs)
Time Frame: From start of study drug administration up to follow-up visit (i.e., up to Week 106)
An adverse event (AE) is any untoward medical occurrence in a clinical investigation participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.
From start of study drug administration up to follow-up visit (i.e., up to Week 106)
Number of Participants Who Will Develop Anti-drug Antibodies (ADA) to REPLAGAL
Time Frame: From Baseline up to Week 104
Number of participants who will develop ADA to REPLAGAL was planned to be reported.
From Baseline up to Week 104

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Shire

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Study Director, Shire

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 28, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 16, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 16, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 7, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 9, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 12, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 17, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 14, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SHP675-301
  • 2018-004689-32 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The study was terminated by the Sponsor due to enrolment challenges. No participants were evaluated, and no data were collected.

IPD Sharing Access Criteria

IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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