NCT02956122终止2 期
A Two-Part, Multi-Center, Prospective, Phase 2/3 Clinical Study to Evaluate the Safety and Efficacy of GLASSIA as an Add-On Biopharmacotherapy to Conventional Steroid Treatment in Subjects With Acute Graft-Versus-Host Disease With Lower Gastrointestinal Involvement
Baxalta now part of Shire1 个研究点 分布在 1 个国家目标入组 1 人开始时间: 2017年4月26日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Percentage of Participants Achieving Overall Response (OR) At Day 28
研究概览
简要总结
The purpose of the study is to evaluate the safety and efficacy of GLASSIA as an add-on biopharmacotherapy to standard-of-care steroid treatment as the first-line treatment in participants with acute GvHD with lower GI involvement.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants aged ≥18 years at the time of screening
- •Recipient of an hematopoietic stem cell transplantation (HSCT)
- •The disease indication for which the participant required HSCT must be in remission
- •Newly diagnosed acute graft-versus-host disease (GvHD), including lower Gastrointestinal (GI) involvement (modified International Bone Marrow Transplant Registry [IBMTR] Severity Stage 1 to 4 [>500 mL diarrhea/day]), with or without other organ system involvement.
- •Willing to undergo or must have had a lower GI biopsy within 7 days of informed consent to confirm GI GvHD. Biopsy results are not needed to initiate treatment; however, if biopsy results are not consistent with aGvHD, treatment with GLASSIA will be discontinued.
- •Participants must be receiving systemic corticosteroids. Treatment with methylprednisolone/systemic steroids must have been initiated within 72 hours prior to the first dose of study treatment after enrollment
- •Evidence of myeloid engraftment (absolute neutrophil count ≥0.5 x 10^9/L)
- •Lower GI GvHD manifested by diarrhea must have other causes of diarrhea ruled out (eg, negative for Clostridium difficile or cytomegalovirus [CMV] infection or oral magnesium administration)
- •Karnofsky Performance Score ≥50%
- •If female of childbearing potential, participant presents with a negative blood pregnancy test
- •Females of childbearing potential with a fertile male sexual partner must agree to employ adequate contraception for the duration of the study.
- •Males must use adequate contraception and must not donate sperm for the duration of the study.
- •Participant is willing and able to comply with the requirements of the protocol
排除标准
- •Participant with manifestations of chronic GvHD
- •Participant with acute/chronic GvHD overlap syndrome
- •Participant whose GvHD developed after donor lymphocyte infusion
- •Participant with myocardial infarction within 6 months prior to enrollment or New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to the first dose of study treatment, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
- •Participant with evidence of recurrent malignancy
- •Participant with veno-occlusive disease (ie, sinusoidal obstruction syndrome)
- •Participant receiving GvHD treatment other than continued prophylaxis (eg, cyclosporine and/or mycophenolate mofetil, etc) or corticosteroid therapy. In addition, a participant who received the first dose of corticosteroid therapy for acute GvHD with lower GI involvement more than 72 hours before the first dose of study treatment is not eligible for the study
- •Participant with severe sepsis involving at least 1 organ failure
- •Participant who is seropositive or positive in the nucleic acid test for human immunodeficiency virus (HIV)
- •Participant with active hepatitis B or C
- •Participant has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study
- •If female, participant is pregnant or lactating at the time of enrollment, or has plans to become pregnant during the study
- •Participant with a serious medical or psychiatric illness likely to interfere with participation in the study
- •Participant is a family member or employee of the investigator
研究组 & 干预措施
Study Part 1 - All Participants - GLASSIA
Experimental
Participants to receive GLASSIA (intravenously) and methylprednisolone or equivalent steroid (either IV or oral per investigator discretion)
干预措施: GLASSIA (Biological)
Study Part 1 - All Participants - GLASSIA
Experimental
Participants to receive GLASSIA (intravenously) and methylprednisolone or equivalent steroid (either IV or oral per investigator discretion)
干预措施: methylprednisolone or equivalent steroid (Drug)
Study Part 2 - GLASSIA
Experimental
Participants to receive GLASSIA (intravenously) and methylprednisolone or equivalent steroid (either IV or oral per investigator discretion)
干预措施: GLASSIA (Biological)
Study Part 2 - GLASSIA
Experimental
Participants to receive GLASSIA (intravenously) and methylprednisolone or equivalent steroid (either IV or oral per investigator discretion)
干预措施: methylprednisolone or equivalent steroid (Drug)
Study Part 2 - Albumin (Control)
Placebo Comparator
Participants to receive control (intravenously) and methylprednisolone or equivalent steroid (either IV or oral per investigator discretion)
干预措施: methylprednisolone or equivalent steroid (Drug)
Study Part 2 - Albumin (Control)
Placebo Comparator
Participants to receive control (intravenously) and methylprednisolone or equivalent steroid (either IV or oral per investigator discretion)
干预措施: Albumin (Biological)
结局指标
主要结局
Percentage of Participants Achieving Overall Response (OR) At Day 28
时间窗: Day 28
OR was defined as graft-versus-host disease (GvHD) complete response (CR) + partial response (PR), defined as: - GvHD CR was complete resolution of all signs and symptoms of acute GvHD in all organs without intervening salvage and GvHD PR was improvement of 1 stage in 1 or more organs involved in GvHD without progression in other organs.
次要结局
- Incidence of Chronic Graft-versus-host Disease (GvHD)(Days 180 and 365)
- Transplant-related Mortality(Days 28, 56, 100 and 180)
- Percentage of Participants Achieving Overall Response at Day 56(Day 56)
- Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180(Days 28, 56 and 180)
- Overall Survival (OS) - Percentage of Participants With an Event(Days 100, 180 and 365)
- Percentage of Participants Achieving Gastrointestinal (GI) Response at Day 28(Day 28)
- Apparent Volume of Distribution at Steady State (Vss) of GLASSIA(Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours)
- Duration of Overall Response (OR)(Baseline up to Day 365)
- Graft-versus-host Disease (GvHD)-Free Survival - Percentage of Participants With an Event(Days 28, 56, 100, 180 and 365)
- Number of Participants With Clinically Significant Changes in Vital Signs(Baseline up to Day 56)
- Number of Participants With Recurrence of Primary Malignancies(Baseline up to Day 365)
- Maximum Observed Plasma Concentration (Cmax) of GLASSIA(Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours)
- Apparent Terminal Half-life (t1/2) of GLASSIA(Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours)
- Duration of Gastrointestinal (GI) Response(Baseline up to Day 365)
- Infection-related Mortality - Percentage of Participants With an Event(Days 28, 56, 100 and 180)
- Number of Participants With Adverse Events (AEs), Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs and Temporally-associated AEs(From start of study drug administration up to 371 days)
- Area Under the Plasma Concentration Curve From Time Zero to Time "t" AUC(0-t) of GLASSIA(Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours)
- Trough Plasma Concentration at Steady State (Ctrough) of GLASSIA(Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours)
- Failure-free Survival - Percentage of Participants With an Event(Days 100 and 180)
- Graft-versus-host Disease (GvHD)-Related Mortality - Percentage of Participants With an Event(Days 28, 56, 100 and 180)
- All-cause Mortality - Percentage of Participants With an Event(Days 28, 56, 100 and 180)
- Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments(Baseline up to Day 56)
- Area Under the Plasma Concentration Curve (AUC0-inf) From Time Zero to Infinity(Day 1: through 48 hours; Day 13: through 48 hours; Day 22 and Day 50: through approximately 168 hours)
- Systemic Clearance at Steady State (CLss) of GLASSIA(Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours)
- Mean Residence Time (MRT) of GLASSIA(Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours)
研究者
研究点 (1)
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