| CTRI Number |
CTRI/2021/12/038690 [Registered on: 16/12/2021] Trial Registered Prospectively |
| Last Modified On: |
17/05/2023 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
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Type of Study
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Biological |
| Study Design |
Single Arm Study |
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Public Title of Study
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A Replagal study in Indian Children and Adults With Fabry Disease
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Scientific Title of Study
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A Prospective, Open-label, Multicentre, Interventional, Single-arm, Phase IV Study to Evaluate the Safety and Efficacy of Agalsidase alfa (r-DNA origin) (Replagalâ„¢) in Indian Children and Adults With Fabry Disease
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| Trial Acronym |
NA |
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Secondary IDs if Any
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| Secondary ID |
Identifier |
| TAK-675-4008 version 2.0 dated 22 February 2021 |
Protocol Number |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
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| Name |
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| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
Modification(s)
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| Name |
Dr Sandeep Arora |
| Designation |
Head Medical Affairs |
| Affiliation |
Takeda Biopharmaceuticals India Pvt. Ltd. |
| Address |
Takeda Biopharmaceuticals India Pvt. Ltd.
6th Floor, Tower C,
Building No. 8,
Cyber City
Gurgaon
HARYANA
122002
India |
| Phone |
91-124-4559100 |
| Fax |
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| Email |
sandeep.arora@takeda.com |
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Details of Contact Person
Public Query
Modification(s)
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| Name |
Ruchi Sogarwal |
| Designation |
Head – Public Affairs & Patient Advocacy |
| Affiliation |
Takeda Biopharmaceuticals India Pvt. Ltd. |
| Address |
Takeda Biopharmaceuticals India Pvt. Ltd.
6th Floor, Tower C,
Building No. 8,
Cyber City
Gurgaon
HARYANA
122002
India |
| Phone |
91-124-4559100 |
| Fax |
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| Email |
ruchi.sogarwal@takeda.com |
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Source of Monetary or Material Support
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| Shire Biotech India Pvt. Ltd. Plot No. 70, A-26, Second Floor, Rama Road, Industrial Area,New Delhi-110015,
India
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Primary Sponsor
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| Name |
Shire Biotech India Pvt Ltd |
| Address |
Shire Biotech India Pvt. Ltd. Plot No. 70, A-26, Second Floor, Rama Road, Industrial Area, New Delhi-110015, India
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| Type of Sponsor |
Pharmaceutical industry-Global |
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Details of Secondary Sponsor
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Countries of Recruitment
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India |
Sites of Study
Modification(s)
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| No of Sites = 5 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Neerja Gupta |
AIIMS |
Department of Pediatrics, Sri Aurobindo Marg, Ansari Nagar, Ansari Nagar East, New Delhi, Delhi 110029
New Delhi
DELHI |
9999995630
neerja17@gmail.com |
| Dr Monjori Mitra |
Institute of Child Health |
Department of Pediatrics, Park Circus, Ballygunge, Kolkata, West Bengal 700017
Kolkata
WEST BENGAL |
9831075734
monjorimr@gmail.com |
| Dr Priyanshu Mathur |
JK Lone Hospital |
Department of Pediatrics Medicine, Jawahar Lal Nehru Marg, Near Trimurti Circle, Gangawal Park, Adarsh Nagar, Jaipur, Rajasthan 302004
Jaipur
RAJASTHAN |
9982451490
priyanshu82@gmail.com |
| Dr Kaushik Mandal |
Sanjay Gandhi Post Graduate Institute of Medical Sciences |
Dept. of Medical Genetics, Raebareli Road, Lucknow, 226014
Lucknow
UTTAR PRADESH |
8765974049
mandal.kausik@gmail.com |
| Dr Ratna Dua Puri |
Sir Gangaram Hospital |
Department of Pediatrics Medicine, Sarhadi Gandhi Marg, Old Rajinder Nagar, Rajinder Nagar, New Delhi, Delhi 110060
New Delhi
DELHI |
9811869192
ratnadpuri@yahoo.com |
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Details of Ethics Committee
Modification(s)
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| No of Ethics Committees= 5 |
| Name of Committee |
Approval Status |
| Institute Ethics committee, All India Institute of Medical sciences Room No.102, 1st Floor,Old O.T Block Ansari Nagar, New Delhi - 110029 |
Submittted/Under Review |
| Institute Ethics Committee, Sanjay Gandhi Post Graduate Institute of Medical Sciences |
Approved |
| Institute of child health Institutional Ethics Committee, Institute of child health Insitutuional Ethics Committee 11,Dr.Biresh Guha Street Kolkota West Bengal - 700017 |
Submittted/Under Review |
| S.M.S. Medical College and Attached Hospitals, S.M.S. Medical College and Attached Hospitals Jawahar Lal Nehru Marg, Near Trimurti Circle, Gangawal Park, Adarsh Nagar, Jaipur, Rajasthan 302004 |
Approved |
| Sir Ganga Ram Hospital Ethics Committee, Sir Gangaram Hospital, Sarhadi Gandhi Marg, Old Rajinder Nagar, Rajinder Nagar, New Delhi, Delhi 110060 |
Submittted/Under Review |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
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| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: E752||Other sphingolipidosis, |
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Intervention / Comparator Agent
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| Type |
Name |
Details |
| Comparator Agent |
Nil |
Nil |
| Intervention |
Replagal |
Each single-use vial of Replagal contains 3.5 mg of agalsidase alfa in 3.5 mL of solution. |
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Inclusion Criteria
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| Age From |
0.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1. Male and female Replagal naïve subjects (and who are not part of any other program at the time of study enrollment and during the study period) of any age with confirmed diagnosis of Fabry disease.
2. Subjects who have documented confirmed diagnosis of Fabry disease based on proof of gene mutation: α-galactosidase A gene compatible with Fabry disease and/or a deficiency of α-galactosidase A (<4.0 nmol/mL/hour in plasma or serum or <8% of average mean normal in leukocytes and sequencing of GLA gene for females).
3. Subject must have any clinical manifestations of Fabry disease based on investigator’s discretion.
4. Subject/LAR/guardian is able to understand and willing to give written informed consent before performing any study specific procedures and willing to adhere to protocol requirements.
5. Female subjects of childbearing potential (eg, nonsterilised, premenopausal female subjects) must have a documented negative pregnancy test prior to administration of the first dose of Replagal in this study. In addition, all female subjects of childbearing potential must use a medically accepted form of contraception throughout the study, ie, either a barrier method or hormonal contraceptive with norethindrone and ethinyl estradiol or similar active components.
6. Male subject who is nonsterilised and sexually active with a female partner of childbearing potential agrees to use barrier method of contraception (eg, condom with or without spermicide) from signing of informed consent throughout the duration of the study.
Note: Female subjects not of childbearing potential defined as those who have been surgically sterilized (hysterectomy, bilateral oophorectomy, or tubal ligation) or who are postmenopausal (eg, defined as at least 1 year since last regular menses with an appropriate clinical profile [ie, age appropriate, history of vasomotor symptoms]
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| ExclusionCriteria |
| Details |
1. Subject who have received Replagal.
2. Subjects with poorly controlled hypertension as per investigator’s discretion.
3. Subjects with chronic kidney disease (CKD) with estimated Glomerular Filtration rate less than 15 mL/min/1.73 m2 and who had/will have kidney transplantation or are currently on dialysis.
4. Subjects with any serious hepatic disorder who had abnormal hepatic function test values at screening (when either ALT or AST level exceeded the value three times the upper limit of normal [ULN] and total bilirubin 1.5 times as high as the ULN); and deemed as clinically significant by investigstor for hematology and biochemistry. These abnormal laboratory values could be discussed with medical monitor before excluding the subject.
5. If female, the subject is pregnant or lactating or intending to become pregnant before participating in this study, during the study; or intending to donate ova during such time period.
6. Subject/LAR/guardian is unable to understand the nature, scope, and possible consequences of the study.
7. Subject 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 safety evaluations, or is otherwise unlikely to complete the study, as determined by the investigator.
8. If male, the subject intends to donate sperm during the course of this study.
9. Subjects who had participated in any other investigational drug study within the past 4 weeks prior to screening.
10. Any subject deemed as unfit for this trial, as per investigator’s clinical judgment.
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Method of Generating Random Sequence
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Not Applicable |
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Method of Concealment
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Not Applicable |
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Blinding/Masking
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Open Label |
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Primary Outcome
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| Outcome |
TimePoints |
| Incidence of adverse events (AEs), serious AEs(SAEs), treatment emergent AEs, treatment emergent SAEs, adverse drug reactions(ADRs), infusion-related reactions, and death |
53 weeks |
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Secondary Outcome
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| Outcome |
TimePoints |
| Changes in estimated glomerular filtration rate (eGFR) |
Baseline to Weeks 13, 27, 39, and 53 |
| Frequency and changes in regimen of analgesic use for neuropathic pain |
Baseline to 53 weeks |
| Changes in urine Gb3 (globotriaosylceramide) |
Baseline to Weeks 13,27,39,and 53 |
| Changes in urine protein/creatinine ratio |
Baseline to Weeks 13, 27, 39, and 53 |
| Percentage changes in left ventricular mass index (LVMI) (g/m2) |
Baseline to Weeks 27 and 53 |
| Percentage changes in left ventricular wall thickness |
Baseline to Weeks 27 and 53 |
| Percentage changes in ejection fraction |
Baseline to Weeks 27 and 53 |
| Changes from baseline to Weeks 27 and 53 in the quality of life based on the questionnaire (36-item short form survey [SF-36]) |
Baseline to Weeks 27 and 53 |
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Target Sample Size
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Total Sample Size="5"
Sample Size from India="5"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
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Phase of Trial
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Phase 4 |
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Date of First Enrollment (India)
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30/12/2021 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
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Estimated Duration of Trial
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Years="3"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
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Not Applicable |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
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Publication Details
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Individual Participant Data (IPD) Sharing Statement
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Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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Brief Summary
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This is a prospective, open-label, multicentre, interventional single-arm Phase IV study to be conducted at approximately 5 sites in India to evaluate the safety and efficacy of Replagal in Indian children and adult population with Fabry disease. A total of 5 subjects with Fabry disease will be enrolled in this study. The total duration of the study for each subject will be up to 55 weeks, consisting of 14 days screening period (Days -14 to -1), a 51 week treatment period (26 doses in 1 year), followed by 2 week follow-up period after the last dose of Replagal (Week 53). At Week 53, the subjects will be assessed for safety and efficacy which will also be considered the end of study (EOS). Subjects who meet all the inclusion criteria and none of the exclusion criteria will be administered Replagal at the site. Subjects will visit the site for dosing on Week 1 (Day 1), followed by every 2 weeks till Week 51 (Day 351). The dose administered on Week 51 will be considered as end of treatment (EOT). The subjects will be followed up for 2 weeks after the last dose of study drug administration for safety and efficacy assessments (EOS Visit). The study drug will be administered as 0.2 mg/kg given intravenously every 2 weeks. The intravenous infusion will be administered over a 40 minutes (±10 minutes).
Efficacy assessments will be done at Screening (Days -14 to -1), Week 13 (Visit 8, Day 85), Week 27 (Visit 15, Day 183), Week 39 (Visit 21, Day 267), and Week 53 (Visit 28/EOS, Day 365). If the subject discontinues study treatment, the subject will have to complete assessments done at Week 53 (Visit 28/EOS). Subjects will be evaluated for safety from initiation of Replagal treatment until 53 weeks (EOS), or until discontinuation of Replagal, whichever occurs earlier.
A subject diary will be provided to the subjects/subject’s parents/guardians/LAR to be filled at home. The diary will be used to capture information of any concomitant medications taken, and other AEs that may occur in between visits.
Apart from that, an unscheduled visit can be performed as per investigator’s discretion or if the trial subject experiences safety concerns. |
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