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

NCT04840667 | Terminated Phase 3 Results

• 2 other identifiers: SHP675-3012018-004689-32
• Study Type: interventional
• Target: 17
• Locations: 8 countries
• Sites: 28

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.

Conditions

Fabry Disease

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Baseline, Week 104

Secondary Outcomes (10)

• Annualized Rate of Change in Estimated Glomerular Filtration Rate (eGFR) up to Week 104

  From Baseline up to Week 104

• Annualized Rate of Change in Left Ventricular Mass Index (LVMI) up to Week 104

  From Baseline up to Week 104

• Change From Baseline in eGFR up to Week 104

  From Baseline up to Week 104

• Change From Baseline in LVMI up to Week 104

  From Baseline up to Week 104

• Change From Baseline in Proteinuria up to Week 104

  From Baseline up to Week 104

Study Arms (1)

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.

Drug: REPLAGAL

Interventions

REPLAGAL DRUG

Participants will receive REPLAGAL 0.2 mg/kg body weight of IV infusion for 104 weeks.

Also known as: SHP675

REPLAGAL

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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 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.

You may not qualify if:

• 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:
• FABRAZYME (agalsidase beta) and its biosimilars
• GLYSET (miglitol)
• ZAVESCA (miglustat)
• CERDELGA (eliglustat)
• GALAFOLD (migalastat)
• Any investigational product for treatment of Fabry disease

Sponsors & Collaborators

• Shire: lead

Study Sites (28)

M.A.G.I.C. Clinic Ltd. Metabolics and Genetics in Calgary

Calgary, AB T2E 7Z4, Canada

Location

Queen Elizabeth II Health Sciences Center

Halifax, B3H 1V7, Canada

Location

Turun Yliopistollinen Keskussairaala

Turku, FI-20521, Finland

Location

Vaasan Keskussairaala

Vaasa, 65130, Finland

Location

Charité - Universitätsklinikum

Berlin, 10117, Germany

Location

SphinCS

Höchheim, 65239, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

Fachinternistische Gemeinschaftspraxis

Müllheim, 79379, Germany

Location

Universitaetsklinikum Wuerzburg

Würzburg, 97080, Germany

Location

Laiko General Hospital of Athens

Athens, 11527, Greece

Location

Attikon University General Hospital

Athens, 12462, Greece

Location

University General Hospital of Heraklion

Heraklion, 71500, Greece

Location

University Hospital of Ioannina

Ioannina, 45500, Greece

Location

Onasseio Private Practise Hospital of Piraeus

Kallithea, 17674, Greece

Location

Papageorgiou General Hospital of Thessaloniki

Thessaloniki, 54645, Greece

Location

Szpital Uniwersytecki

Krakow, 30-033, Poland

Location

Narodowy Instytut Kardiologii im Prymasa Tysiaclecia Kardynala Stefana Wyszynskiego - Instytut Badaw

Warsaw, 04-628, Poland

Location

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu

Wroclaw, 50-556, Poland

Location

Centro Hospitalar e Universitário de Coimbra EPE

Coimbra, 3000-459, Portugal

Location

Hospital Senhora da Oliveira - Guimaraes, E.P.E

Guimarães, 4835-044, Portugal

Location

Centro Hospitalar Lisboa Norte, E.P.E. - Hospital de Santa Maria

Lisbon, 1649-035, Portugal

Location

Hospital General Universitario de Alicante

Alicante, 3010, Spain

Location

Hospital de Torrecárdenas

Almería, 4009, Spain

Location

Hospital Universitario Vall d'Hebrón - PPDS

Barcelona, 8035, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocio - PPDS

Seville, 41013, Spain

Location

Hospital Quironsalud Zaragoza

Zaragoza, 50012, Spain

Location

Akademiska Sjukhuset I Uppsala

Uppsala, 75185, Sweden

Location

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Conditions

Fabry Disease

Interventions

agalsidase alfa

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Limitations and Caveats

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

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@takeda.com

+1 866 842 5335

Study Officials

• Study Director

  Shire

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2020
• First Posted: April 12, 2021
• Study Start: December 28, 2021
• Primary Completion: December 16, 2022
• Study Completion: December 16, 2022
• Last Updated: June 17, 2024
• Results First Posted: June 17, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

PL (3); ES (6); CA (2); PT (3); DE (5); GR (6); SE (1); FI (2)