A Phase III, Randomized, Double-blind Study of Ianalumab (VAY736) Versus Placebo in Addition to First-line Corticosteroids in Primary Immune Thrombocytopenia (VAYHIT1)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 226
- 试验地点
- 135
- 主要终点
- Time from randomization to treatment failure (TTF)
研究概览
简要总结
The purpose of this study is to evaluate the effect of two different doses of ianalumab versus placebo in addition to first-line corticosteroids in maintaining platelet count ≥30 G/L in adult participants with primary ITP.
详细描述
This is a multi-center, randomized, double-blind Phase 3 study to assess the efficacy and safety of two different doses of ianalumab compared to placebo in adults with primary ITP (platelets count <30 G/L) who require first-line standard-of-care corticosteroids.
After completion of the screening period, the participants will enter the randomized treatment period (ianalumab/placebo with standard of care corticosteroids).
After the treatment period, all participants will enter the follow-up period to be monitored for efficacy and safety or safety only depending on how they respond to the study treatment.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent prior to participation in the study.
- •Male or female participants aged 18 years and older on the day of signing informed consent
- •Primary ITP diagnosed within 3 months before initiating first-line ITP therapy (corticosteroids, IVIG)
- •Platelet count below 30 G/L before starting any first-line ITP therapy (corticosteroids, IVIG)
- •Response (platelet count >=50 G/L) to corticosteroids (+/- IVIG) at any time prior to randomization. Note: Platelet count measured within 7 days of platelet transfusion will not be considered as response.
排除标准
- •Evans syndrome or any other cytopenia (patients with low grade anemia related to bleeding or iron deficiency are eligible)
- •Current life-threatening bleeding
- •Previous ITP treatment, including splenectomy, except for corticosteroids and/or IVIG initiated as first-line therapy for up to 28 days before randomization and rescue corticosteroids and/or IVIG given prior to confirmed diagnosis of primary ITP .
- •Prior use of B-cell depleting therapy (e.g., rituximab).
- •Absolute neutrophil count below 1.0 G/L at randomization
- •Participants with concurrent coagulation disorders and/or receiving anti-platelet or anticoagulant medication with an exemption of low dose of acetylsalicylic acid
- •Other protocol-defined Inclusion/Exclusion may apply.
研究组 & 干预措施
Ianalumab Lower dose
Lower dose of ianalumab administered intravenously with corticosteroids oral or parental (if clinically justified)
干预措施: Ianalumab (Biological)
Ianalumab Lower dose
Lower dose of ianalumab administered intravenously with corticosteroids oral or parental (if clinically justified)
干预措施: Corticosteroids (Drug)
Ianalumab Higher dose
Higher dose of ianalumab administered intravenously with corticosteroids oral or parental (if clinically justified)
干预措施: Ianalumab (Biological)
Ianalumab Higher dose
Higher dose of ianalumab administered intravenously with corticosteroids oral or parental (if clinically justified)
干预措施: Corticosteroids (Drug)
Placebo
Placebo administered intravenously with corticosteroids oral or parental (if clinically justified)
干预措施: Placebo (Drug)
Placebo
Placebo administered intravenously with corticosteroids oral or parental (if clinically justified)
干预措施: Corticosteroids (Drug)
结局指标
主要结局
Time from randomization to treatment failure (TTF)
时间窗: Randomization to end of study (up to 39 months after randomization of last patient)
Time from randomization until platelet count below 30 G/L, need for a rescue treatment or start of a second-line therapy or death.
次要结局
- Complete Response (CR) rate in each treatment group(Randomization to end of study (up to 39 months after randomization of last patient))
- Response (R) rate in each treatment group(Randomization to end of study (up to 39 months after randomization of last patient))
- Time to complete response in each treatment group(Randomization to end of study (up to 39 months after randomization of last patient))
- Duration of response in each treatment group(Randomization to end of study (up to 39 months after randomization of last patient))
- Stable response at 6 months(At 6 months)
- Stable response at 1 year(At 1 year)
- Percentage of participants with bleeding events overall and by World Health Organization (WHO) bleeding scale severity(Randomization to end of study (up to 39 months after randomization of last patient))
- Number of participants with bleeding events overall and by World Health Organization (WHO) bleeding scale severity(Randomization to end of study (up to 39 months after randomization of last patient))
- Number of participants receiving rescue treatment (cummulative dose/duration of steroids exposure)(Randomization to end of study (up to 39 months after randomization of last patient))
- Percentage of participants receiving rescue treatment (cummulative dose/duration of steroids exposure)(Randomization to end of study (up to 39 months after randomization of last patient))
- Cumulative dose/duration of steroids exposure(From screening to end of study (up to 39 months after randomization of last patient))
- Change from baseline on T scores of the PROMIS SF v1.0 Fatigue 13a(From screening (baseline) till end of study (up to 39 months after randomization of last patient))
- Change from baseline in ITP-PAQ domain scores(From screening (baseline) till end of study (up to 39 months after randomization of last patient))
- Change from baseline in frequency of CD19+ B cell counts(Randomization to end of study (up to 39 months after randomization of last patient))
- Change from baseline in absolute number of CD19+ B cell counts(Randomization to end of study (up to 39 months after randomization of last patient))
- Time to first occurrence of B-cell recovery(Randomization to end of study (up to 39 months after randomized of last patient))
- Change from baseline in inmmunoglobulins(Randomization to end of study (up to 39 months after last randomized patients))
- PK parameters: AUClast(After first dose (pre-dose, 2, 168, 336 and 504 hours post dose) and after last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose))
- PK parameter: AUCtau(After first dose (pre-dose, 2, 168, 336 and 504 hours post dose) and after last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose))
- PK parameters: Cmax(After first dose (pre-dose, 2, 168, 336 and 504 hours post dose) and after last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose))
- PK parameters: Tmax(After first dose (pre-dose, 2, 168, 336 and 504 hours post dose) and after last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose))
- PK parameters: Accumulation ratio Racc(After last dose (pre-dose, 2, 336, 672, 1344, 2016, 3360 hours post dose))
- Incidence of anti-ianalumab antibodies in serum (ADA assay) over time(Up to Week 33)
- Titer of anti-ianalumab antibodies in serum (ADA assay) over time(Up to Week 33)