Clinical trial NCT05067868: A Study of Replagal in Children and Adults With Fabry Disease in India
Official title: A Prospective, Open-label, Multicentre, Interventional, Single-arm, Phase IV Study to Evaluate the Safety and Efficacy of Agalsidase Alfa (r-DNA Origin) (Replagal™) in Indian Children and Adults With Fabry Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Fabry Disease
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2021-10-05
Enrollment: 5
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main aim of this study is to learn more about the safety profile of Replagal.

Participants will receive Replagal every 2 weeks at the clinic for about 1 year.


Eligibility criteria: Inclusion Criteria:

1. Male and female Replagal naïve participants (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. Participants 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 (less than \[\<\] 4.0 nanomol per milliliter per hour (nmol/mL/hour) in plasma or serum or \<8 percent (%) of average mean normal in leukocytes and sequencing of GLA gene for females).
3. Participant must have any clinical manifestations of Fabry disease based on investigator's discretion.
4. Participant/legal authorized representative (LAR)/guardian must be 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 participants of childbearing potential (example, nonsterilised, premenopausal female participants) must have a documented negative pregnancy test prior to administration of the first dose of Replagal in this study. In addition, all female participants of childbearing potential must use a medically accepted form of contraception throughout the study, that is, either a barrier method or hormonal contraceptive with norethindrone and ethinyl estradiol or similar active components.
6. Male participant who is nonsterilised and sexually active with a female partner of childbearing potential agrees to use barrier method of contraception (example, condom with or without spermicide) from signing of informed consent throughout the duration of the study.

Note: Female participants not of childbearing potential defined as those who have been surgically sterilized (hysterectomy, bilateral oophorectomy, or tubal ligation) or who are postmenopausal (example, defined as at least 1 year since last regular menses with an appropriate clinical profile \[that is, age appropriate, history of vasomotor symptoms\]).

Exclusion Criteria:

1. Participants who have received Replagal.
2. Participants with poorly controlled hypertension as per investigator's discretion.
3. Participants with chronic kidney disease (CKD) with estimated Glomerular Filtration rate less than 15 milliliter per minute (mL/min) /1.73 meter square (m\^2) and who had/will have kidney transplantation or are currently on dialysis.
4. Participants with any serious hepatic disorder who had abnormal hepatic function test values at screening (when either alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] 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 investigator for hematology and biochemistry. These abnormal laboratory values could be discussed with medical monitor before excluding the participant.
5. If female, the participant 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. Participant/LAR/guardian is unable to understand the nature, scope, and possible consequences of the study.
7. Participant is unable to comply with the protocol, example, 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 participant intends to donate sperm during the course of this study.
9. Participants who had participated in any other investigational drug study within the past 4 weeks prior to screening.
10. Any participant deemed as unfit for this trial, as per investigator's clinical judgment.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From the start of study up to 53 weeks
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: From the study drug administration up to Week 53
measure: Number of Participants With Adverse Drug Reactions (ADRs) Related to Replagal
timeFrame: From the study drug administration up to Week 53
measure: Number of Participants With Infusion-related Reactions of Replagal
timeFrame: From the study drug administration up to Week 53
measure: Number of Participants With Death
timeFrame: From the study drug administration up to Week 53
Secondary outcomes:
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Baseline and at Weeks 13, 27, 39, and 53
measure: Number of Participants With Change in Frequency and Regimen of Analgesic use of Replagal for Neuropathic Pain
timeFrame: Baseline up to Week 53
measure: Change From Baseline in Urine Concentration of Globotriaosylceramide (Gb3)
timeFrame: Baseline and at Weeks 13, 27, 39, and 53
measure: Change From Baseline in Urine Protein Creatinine Ratio
timeFrame: Baseline and at Weeks 13, 27, 39, and 53
measure: Percent Change From Baseline in Left Ventricular Mass Index (LVMI)
timeFrame: Baseline and at Weeks 27 and 53
measure: Percent Change From Baseline in Left Ventricular Wall Thickness
timeFrame: Baseline and at Weeks 27 and 53
measure: Percent Change From Baseline in Ejection Fraction
timeFrame: Baseline and at Weeks 27 and 53
measure: Percent Change From Baseline in Quality of Life Based on Questionnaire 36-itme Form Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores)
timeFrame: Baseline and at Weeks 27 and 53
Other outcomes:
Locations:
city: Hyderabad
country: India
facility: Rainbow Super Specialty Hospital
city: Jaipur
country: India
facility: J K Lone Hospital
city: Kolkata
country: India
facility: Institute of Child Health
city: New Delhi
country: India
facility: All India Institute of Medical Sciences (AIIMS)
city: New Delhi
country: India
facility: Sir Gangaram Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: