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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04840667




Registration number
NCT04840667
Ethics application status
Date submitted
7/07/2020
Date registered
12/04/2021
Date last updated
6/05/2023

Titles & IDs
Public title
A Study of Replagal in Treatment-naïve Adults With Fabry Disease
Scientific title
A Phase 3, Open-label Study to Evaluate the Efficacy and Safety of REPLAGAL® in Treatment-naïve Subjects With Fabry Disease
Secondary ID [1] 0 0
2018-004689-32
Secondary ID [2] 0 0
SHP675-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fabry Disease 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - REPLAGAL

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.


Treatment: Drugs: REPLAGAL
Participants will receive REPLAGAL 0.2 mg/kg body weight of IV infusion for 104 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Renal Function at Week 104
Timepoint [1] 0 0
Baseline, Week 104
Primary outcome [2] 0 0
Change From Baseline in Cardiac Structure at Week 104
Timepoint [2] 0 0
Baseline, Week 104
Secondary outcome [1] 0 0
Annualized Rate of Change in Estimated Glomerular Filtration Rate (eGFR) up to Week 104
Timepoint [1] 0 0
Baseline, up to Week 104
Secondary outcome [2] 0 0
Annualized Rate of Change in Left Ventricular Mass Index (LVMI) up to Week 104
Timepoint [2] 0 0
Baseline, up to Week 104
Secondary outcome [3] 0 0
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) up to Week 104
Timepoint [3] 0 0
Baseline, up to Week 104
Secondary outcome [4] 0 0
Change From Baseline in Left Ventricular Mass Index (LVMI) up to Week 104
Timepoint [4] 0 0
Baseline, up to Week 104
Secondary outcome [5] 0 0
Change From Baseline in Proteinuria up to Week 104
Timepoint [5] 0 0
Baseline, up to Week 104
Secondary outcome [6] 0 0
Change From Baseline in Cardiac Fibrotic Segments up to Week 104
Timepoint [6] 0 0
Baseline, up to Week 104
Secondary outcome [7] 0 0
Change From Baseline in Interventricular Septal End-Diastolic Thickness and Posterior Wall Thickness in Diastole up to Week 104
Timepoint [7] 0 0
Baseline, up to Week 104
Secondary outcome [8] 0 0
Change From Baseline in Plasma Globotriaosylsphingosine (lyso-Gb3) up to Week 104
Timepoint [8] 0 0
Baseline, up to Week 104
Secondary outcome [9] 0 0
Number of Participants with Adverse Events (AEs)
Timepoint [9] 0 0
From start of study drug administration up to follow-up (Week 106)
Secondary outcome [10] 0 0
Number of Participants Who Will Develop Anti-drug Antibodies (ADA) to REPLAGAL
Timepoint [10] 0 0
Baseline, up to Week 104

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/12/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/12/2022
Sample size
Target
Accrual to date
Final
17
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Calgary
Country [2] 0 0
Canada
State/province [2] 0 0
Halifax
Country [3] 0 0
Finland
State/province [3] 0 0
Turku
Country [4] 0 0
Finland
State/province [4] 0 0
Vaasa
Country [5] 0 0
Germany
State/province [5] 0 0
Berlin
Country [6] 0 0
Germany
State/province [6] 0 0
Hochheim
Country [7] 0 0
Germany
State/province [7] 0 0
Mainz
Country [8] 0 0
Germany
State/province [8] 0 0
Müllheim
Country [9] 0 0
Germany
State/province [9] 0 0
Wuerzburg
Country [10] 0 0
Greece
State/province [10] 0 0
Athens
Country [11] 0 0
Greece
State/province [11] 0 0
Heraklion
Country [12] 0 0
Greece
State/province [12] 0 0
Ioannina
Country [13] 0 0
Greece
State/province [13] 0 0
Kallithea
Country [14] 0 0
Greece
State/province [14] 0 0
Thessaloniki
Country [15] 0 0
Poland
State/province [15] 0 0
Krakow
Country [16] 0 0
Poland
State/province [16] 0 0
Warszawa
Country [17] 0 0
Poland
State/province [17] 0 0
Wroclaw
Country [18] 0 0
Portugal
State/province [18] 0 0
Coimbra
Country [19] 0 0
Portugal
State/province [19] 0 0
Guimaraes
Country [20] 0 0
Portugal
State/province [20] 0 0
Lisboa
Country [21] 0 0
Spain
State/province [21] 0 0
Alicante
Country [22] 0 0
Spain
State/province [22] 0 0
Almeria
Country [23] 0 0
Spain
State/province [23] 0 0
Barcelona
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid
Country [25] 0 0
Spain
State/province [25] 0 0
Sevilla
Country [26] 0 0
Spain
State/province [26] 0 0
Zaragoza
Country [27] 0 0
Sweden
State/province [27] 0 0
Uppsala

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Shire
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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. 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04840667
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Shire
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04840667