Fabry DiseasePhase 3NCT04840667
A Study of Replagal in Treatment-naïve Adults With Fabry Disease
A Phase 3 study testing REPLAGAL in people with Fabry Disease, run by Shire at 28 sites in 8 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Fabry Disease
- What is being tested?
- REPLAGAL
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 28 sitesin 8 countries
- Study dates
- 28 Dec 2021to 16 Dec 2022
- Phase
- Phase 3
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- For male participants, Fabry disease is confirmed by a deficiency of alpha-galactosidase A (GLA) activity and a mutation in the GLA gene
- 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.
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- 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.
Who cannot join
- 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.
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- 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:
- FABRAZYME (agalsidase beta) and its biosimilars
- GLYSET (miglitol)
- ZAVESCA (miglustat)
- CERDELGA (eliglustat)
- GALAFOLD (migalastat)
- Any investigational product for treatment of Fabry disease
- Treatment at any time during the study with the following medications:
- Chloroquine
- Amiodarone
- Monobenzone
- 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.
Trial locations and contacts
28 sites in 8 countries.
28 sites in 8 countries
Greece6 sites
Laiko General Hospital of Athens
Athens, 11527
Attikon University General Hospital
Athens, 12462
University General Hospital of Heraklion
Heraklion, 71500
University Hospital of Ioannina
Ioannina, 45500
Onasseio Private Practise Hospital of Piraeus
Kallithea, 17674
Papageorgiou General Hospital of Thessaloniki
Thessaloniki, 54645
Spain6 sites
Hospital General Universitario de Alicante
Alicante, 3010
Hospital de Torrecárdenas
Almería, 4009
Hospital Universitario Vall d'Hebrón - PPDS
Barcelona, 8035
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario Virgen del Rocio - PPDS
Seville, 41013
Hospital Quironsalud Zaragoza
Zaragoza, 50012
Germany5 sites
Charité - Universitätsklinikum
Berlin, 10117
SphinCS
Höchheim, 65239
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, 55131
Fachinternistische Gemeinschaftspraxis
Müllheim, 79379
Universitaetsklinikum Wuerzburg
Würzburg, 97080
Poland3 sites
Szpital Uniwersytecki
Krakow, 30-033
Narodowy Instytut Kardiologii im Prymasa Tysiaclecia Kardynala Stefana Wyszynskiego - Instytut Badaw
Warsaw, 04-628
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
Wroclaw, 50-556
Portugal3 sites
Centro Hospitalar e Universitário de Coimbra EPE
Coimbra, 3000-459
Hospital Senhora da Oliveira - Guimaraes, E.P.E
Guimarães, 4835-044
Centro Hospitalar Lisboa Norte, E.P.E. - Hospital de Santa Maria
Lisbon, 1649-035
Canada2 sites
M.A.G.I.C. Clinic Ltd. Metabolics and Genetics in Calgary
Calgary, AB T2E 7Z4
Queen Elizabeth II Health Sciences Center
Halifax, B3H 1V7
Finland2 sites
Turun Yliopistollinen Keskussairaala
Turku, FI-20521
Vaasan Keskussairaala
Vaasa, 65130
About this study
Official title: 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.
- Conditions
- Fabry Disease
- Being tested
- REPLAGAL
- Medical subject headings
- Fabry Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
REPLAGALDrug
Also called SHP675
Participants will receive REPLAGAL 0.2 mg/kg body weight of IV infusion for 104 weeks.
| Study group | Role | What they receive |
|---|---|---|
| REPLAGAL | Experimental | Participants will receive REPLAGAL 0.2 milligram per kilogram (mg/kg) body weight of intravenous (IV) infusion Every Other Week (EOW) for 104 weeks. Receives: Drug: REPLAGAL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Renal Function at 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.
Measured: Baseline, Week 104
Change From Baseline in Cardiac Structure at 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.
Measured: Baseline, Week 104
Secondary outcomes (10)
Annualized Rate of Change in Estimated Glomerular Filtration Rate (eGFR) up to Week 104
Annualized rate of change in eGFR up to Week 104 was planned to be reported.
Measured: From Baseline up to Week 104
Annualized Rate of Change in Left Ventricular Mass Index (LVMI) up to Week 104
Annualized rate of change in LVMI up to Week 104 was planned to be reported.
Measured: From Baseline up to Week 104
Change From Baseline in eGFR up to Week 104
Change from baseline in eGFR up to Week 104 was planned to be reported.
Measured: From Baseline up to Week 104
Change From Baseline in LVMI up to Week 104
Change from baseline in LVMI up to Week 104 was planned to be reported.
Measured: From Baseline up to Week 104
Change From Baseline in Proteinuria 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.
Measured: From Baseline up to Week 104
Change From Baseline in Cardiac Fibrotic Segments 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.
Measured: 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
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.
Measured: From Baseline up to Week 104
Change From Baseline in Plasma Globotriaosylsphingosine (Lyso-Gb3) up to Week 104
Change from baseline in lyso-Gb3 up to Week 104 was planned to be reported.
Measured: From Baseline up to Week 104
Number of Participants With Adverse Events (AEs)
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.
Measured: 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
Number of participants who will develop ADA to REPLAGAL was planned to be reported.
Measured: From Baseline up to Week 104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2021
- Study start28 Dec 2021
- Primary completion16 Dec 2022
- Study completion16 Dec 2022
Why it stopped: Study closed due to enrolment challenges, not for any safety issues
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.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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, Shire
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04840667
- Sponsor's protocol ID
- SHP675-301
- Other IDs
- 2018-004689-32, 2018
- Status last verified
- Jun 2024
- First submitted
- 7 Jul 2020
- Last updated
- 17 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The study was terminated by the Sponsor due to enrolment challenges. No participants were evaluated, and no data were collected.
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Open-label Study to Evaluate the Efficacy and Safety of REPLAGAL® in Treatment-naïve Subjects With Fabry Disease
- ClinicalTrials.gov ID
- NCT04840667
- Acronym / sponsor ID
- SHP675-301
- Conditions
- Fabry Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study closed due to enrolment challenges, not for any safety issues
- Enrolment
- 17 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 28 Dec 2021 (actual)
- Primary completion
- 16 Dec 2022 (actual)
- Study completion
- 16 Dec 2022 (actual)
- First posted
- 12 Apr 2021 (actual)
- Results
- Posted 17 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| REPLAGAL | Experimental | Drug: REPLAGALParticipants will receive REPLAGAL 0.2 milligram per kilogram (mg/kg) body weight of intravenous (IV) infusion Every Other Week (EOW) for 104 weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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:
- 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.
Key exclusion criteria (25 listed)
- 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.
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 |
|---|---|---|
| REPLAGALAlso: SHP675Participants will receive REPLAGAL 0.2 mg/kg body weight of IV infusion for 104 weeks. | Drug | REPLAGAL |
Primary outcome
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.
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.
10 secondary outcomes
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 Left Ventricular Mass Index (LVMI) up to Week 104
Time frame: 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 LVMI up to Week 104
Time frame: From Baseline up to Week 104
Change From Baseline in Proteinuria up to Week 104
Time frame: 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 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 Plasma Globotriaosylsphingosine (Lyso-Gb3) up to Week 104
Time frame: 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)
Number of Participants Who Will Develop Anti-drug Antibodies (ADA) to REPLAGAL
Time frame: From Baseline up to Week 104
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain more information on the study, click here/on this linkLink provided by the sponsor.
- Individual participant dataSharing planned: No. The study was terminated by the Sponsor due to enrolment challenges. No participants were evaluated, and no data were collected.
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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
Shire
28 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing REPLAGAL in people with Fabry Disease, run by Shire at 28 sites in 8 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 25 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: stopped early, as of the sponsor's last update on 17 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in Greece, Spain, Germany, Poland, Portugal and 3 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 17 Jun 2024). 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?
Change From Baseline in Renal Function at Week 104 (time frame: Baseline, Week 104). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Jun 2024.