A Prospective, Open-label, Multicentre, Interventional, Single-arm, Phase IV Study to Evaluate the Safety and Efficacy of Replagal (Agalsidase Alfa [r-DNA Origin]) in Indian Children and Adults With Fabry Disease
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- Shire
- 入组人数
- 5
- 试验地点
- 6
- 主要终点
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female Replagal naïve participants (and who are not part of any other program that allows participant to get access to free enzyme replacement therapy [ERT] at the time of study enrollment and during the study period) of any age with confirmed diagnosis of Fabry disease.
- •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 nanomole 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).
- •Participant must have any clinical manifestations of Fabry disease based on investigator's discretion.
- •Participant/legal authorized representative (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.
- •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 two medically accepted forms of contraception throughout the study, that is, either a barrier method or hormonal contraceptive with norethindrone and ethinyl estradiol or similar active components.
- •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]).
排除标准
- •Participants who have received Replagal.
- •Participants with poorly controlled hypertension as per investigator's discretion.
- •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.
- •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.
- •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.
- •Participant/LAR/guardian is unable to understand the nature, scope, and possible consequences of the study.
- •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.
- •If male, the participant intends to donate sperm during the course of this study.
- •Participants who had participated in any other investigational drug study within the past 4 weeks prior to screening.
- •Any participant deemed as unfit for this trial, as per investigator's clinical judgment.
研究组 & 干预措施
Replagal
Participants with fabry disease will receive Replagal 0.2 milligram per kilogram (mg/kg) intravenous infusion on Day 1 and every 2 weeks up to Week 51.
干预措施: Replagal (Biological)
结局指标
主要结局
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From the start of study up to 53 weeks
An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical (study) product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (study) product, whether or not related to the medicinal (study) product. An SAE is any untoward medical occurrence (whether considered to be related to study product or not) that at any dose results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality or birth defect, an important medical event.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
时间窗: From the study drug administration up to Week 53
AE is any unfavorable and unintended sign, symptom, or disease temporally associated with study or use of investigational drug product (IP), whether or not the AE is considered related to IP. TEAEs: AEs occurring or worsening at or after first dose of IP or ongoing at time of enrollment. SAE :untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. Severity: Mild: event that does not generally interfere with usual activities of daily living; Moderate: event that interferes with usual activities of daily living, causing discomfort, permanent risk of harm; Severe: AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention.
Number of Participants With Adverse Drug Reactions (ADRs) Related to Replagal
时间窗: From the study drug administration up to Week 53
An ADR is defined as a response to a drug which is noxious and unintended, and which occurs at doses normally used in humans for prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function. Number of participants with ADRs will be reported.
Number of Participants With Infusion-related Reactions of Replagal
时间窗: From the study drug administration up to Week 53
Number of participants with infusion-related reactions of Replagal will be reported.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From the start of study up to 53 weeks
An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical (study) product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (study) product, whether or not related to the medicinal (study) product. An SAE is any untoward medical occurrence (whether considered to be related to study product or not) that at any dose results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality or birth defect, an important medical event.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
时间窗: From the study drug administration up to Week 53
AE is any unfavorable and unintended sign, symptom, or disease temporally associated with study or use of investigational drug product (IP), whether or not the AE is considered related to IP. TEAEs: AEs occurring or worsening at or after first dose of IP or ongoing at time of enrollment. SAE :untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. Severity: Mild: event that does not generally interfere with usual activities of daily living; Moderate: event that interferes with usual activities of daily living, causing discomfort, permanent risk of harm; Severe: AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention.
Number of Participants With Adverse Drug Reactions (ADRs) Related to Replagal
时间窗: From the study drug administration up to Week 53
An ADR is defined as a response to a drug which is noxious and unintended, and which occurs at doses normally used in humans for prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function. Number of participants with ADRs will be reported.
Number of Participants With Infusion-related Reactions of Replagal
时间窗: From the study drug administration up to Week 53
Number of participants with infusion-related reactions of Replagal will be reported.
次要结局
- Change From Baseline in Urine Concentration of Globotriaosylceramide (Gb3)(Baseline and at Weeks 13, 27, 39, and 53)
- Number of Participants With Change in Frequency and Regimen of Analgesic use of Replagal for Neuropathic Pain(Baseline up to Week 53)
- 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)(Baseline and at Weeks 27 and 53)
- Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)(Baseline and at Weeks 13, 27, 39, and 53)
- Change From Baseline in Urine Protein Creatinine Ratio(Baseline and at Weeks 13, 27, 39, and 53)
- Percent Change From Baseline in Left Ventricular Mass Index (LVMI)(Baseline and at Weeks 27 and 53)
- Percent Change From Baseline in Left Ventricular Wall Thickness(Baseline and at Weeks 27 and 53)
- Percent Change From Baseline in Ejection Fraction(Baseline and at Weeks 27 and 53)