A Phase 2 Open-label Study to Evaluate the Tolerability of Ianalumab (VAY736) With Investigator's Choice Thrombopoietin Receptor Agonist (IC TPO-RA) in Patients With Primary Immune Thrombocytopenia (ITP) Previously Treated With at Least One Treatment (VAY2EXPLORE)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 164
- 试验地点
- 13
- 主要终点
- (Main cohort: Primary immune thrombocytopenia (ITP)): Percentages of participants who are tolerable to ianalumab (9 mg/kg)
研究概览
简要总结
The purpose of this study is to investigate the tolerability of ianalumab (9 mg/kg) with investigator's choice thrombopoietin receptor agonist (IC TPO-RA) in participants diagnosed with primary immune thrombocytopenia (ITP) who have been treated with at least one but no more than four prior treatments, and with no change in IC TPO-RA dose in at least the last 14 days prior to the start of ianalumab.
详细描述
The study will include an exploratory cohort of participants with primary Evans syndrome (ES) for whom IC TPO-RA therapy is appropriate per investigator's assessment.
The study will consist of a 28-day screening period; a 16-week treatment period; an IC TPO-RA tapering period during which all participants will be monitored for 16 weeks. All participants will then continue to be followed for another 60-weeks (15 months) of long-term safety follow-up period.
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
- None
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
- •Signed informed consent must be obtained prior to participation in the study.
- •Patients aged 18 years and older on the day of signing the informed consent.
- •ITP cohort only: Confirmed diagnosis of primary ITP that has previously responded to corticosteroid treatment or IVIG treatment but the response was not sustained (response is defined as a platelet count ≥ 50 G/L).
- •ITP cohort only: Received at least one prior treatment for ITP.
- •ITP cohort only: Patients with a platelet count < 100 G/L who are receiving a TPO-RA. Patients may already be receiving a TPO-RA or may start a TPO-RA at the time of screening. All patients should be on a stable dose of TPO-RA for at least 14 days prior to first dose of ianalumab. Note: during the screening period, a documented assessment of platelets < 100 G/L is mandatory for enrollment. For patients who received rescue medication before screening, platelet count results obtained prior to the start of the rescue therapy should be used to assess eligibility if collected within 14 days prior to screening.
- •ES cohort only: Patients with clinical diagnosis of primary ES with active thrombocytopenia (< 100 G/L) with warm autoimmune hemolytic anemia (wAIHA) for whom a TPO-RA is appropriate per Investigator.
- •ES cohort only: Inadequate response to or relapse after treatment with corticosteroid therapy.
- •ES cohort only: Diagnosis confirmed by current or past positive direct antiglobulin test (DAT) (IgG+, with or without C3+) and evidence of hemolysis.
- •ES cohort only: any supportive care treatment administered for wAIHA must be stable for at least 4 weeks prior to enrollment.
排除标准
- •Patients being treated with TPO-RA for > 6 months.
- •Current life-threatening bleeding (related to thrombocytopenia).
- •Prior splenectomy within 6 months of first administration of ianalumab.
- •Patients with the following laboratory abnormalities:
- •Neutrophils: < 1000/mm3
- •Serum creatinine > 1.5 × upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) > 3.0 × ULN
- •Alanine aminotransferase (ALT) > 3.0 × ULN
- •Immunoglobulin G (IgG) < 5 g/L
- •ITP cohort only: hemoglobin < 10 g/L, total bilirubin > 1.5 × ULN
- •Patients with significantly compromised liver disease (Child-Pugh 7 to 9) and decompensated liver disease (Child-Pugh 10 to 15).
- •Treatment with a B-cell depleting therapy (e.g. rituximab or anti-B cell Activating Factor (e.g. belimumab) within 12 weeks prior to the first administration of ianalumab. Patients who are refractory to rituximab will be excluded from this trial, where refractory is defined as:
- •~ Patients who have not achieved a response (defined as platelet count ≥ 30 G/L and at least doubling from baseline within 12 weeks in the absence of rescue therapy) following completion of a standard course of rituximab
- •History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes.
- •Known history of primary or secondary immunodeficiency, or a positive human immunodeficiency virus (HIV) enzyme-linked immunosorbent assay (ELISA) and Western blot) test result.
- •Patients exposed to more than 4 prior treatments for ITP.
- •ITP cohort only: Diagnosis of secondary thrombocytopenia.
- •ITP cohort: Use of immunosuppressant drugs other than corticosteroids or rituximab.
- •ES cohort only: Diagnosis of secondary ES.
- •ES cohort only: Life-threatening hemolysis.
- •ES cohort only: patients with autoimmune hemolytic anemia other than wAIHA
研究组 & 干预措施
Main cohort: Primary immune thrombocytopenia (ITP)
All participants will be assigned to ianalumab 9 mg/kg plus investigator's choice thrombopoietin receptor agonist (IC TPO-RA).
干预措施: thrombopoietin receptor agonist (TPO-RA) (Drug)
Main cohort: Primary immune thrombocytopenia (ITP)
All participants will be assigned to ianalumab 9 mg/kg plus investigator's choice thrombopoietin receptor agonist (IC TPO-RA).
干预措施: ianalumab (Biological)
Exploratory cohort: Primary Evans syndrome (ES)
All participants will be assigned to ianalumab 9 mg/kg plus investigator's choice thrombopoietin receptor agonist (IC TPO-RA).
干预措施: thrombopoietin receptor agonist (TPO-RA) (Drug)
Exploratory cohort: Primary Evans syndrome (ES)
All participants will be assigned to ianalumab 9 mg/kg plus investigator's choice thrombopoietin receptor agonist (IC TPO-RA).
干预措施: ianalumab (Biological)
结局指标
主要结局
(Main cohort: Primary immune thrombocytopenia (ITP)): Percentages of participants who are tolerable to ianalumab (9 mg/kg)
时间窗: Up to Week 16
The proportion of participants who tolerate ianalumab (9 mg/kg) is defined as those who do not experience any of the following events during the combination treatment period (up to Week 16): * Discontinuation due to an adverse event (AE) unrelated to efficacy * Adverse events leading to dose reduction or dose rate reduction * Adverse events resulting in study drug interruption.
次要结局
- (Main cohort: Primary immune thrombocytopenia (ITP)): Incidence rate of Adverse Events(From Week 1 Day 1 (first dose of ianalumab) to the end of study (EOS), an average of 4 years)
- (Main cohort: Primary immune thrombocytopenia (ITP)): Percentage of participants with platelet count ≥ 30 G/L, ≥ 50 G/L, ≥ 100 G/L(Baseline, and at each scheduled study visit until the end of study (EOS), an average of 2 years)
- (Main cohort: Primary immune thrombocytopenia (ITP)): Change from baseline in platelet count for prespecified subgroups (<30, 30 to 50, 50 to <100 G/L)(Baseline, and at each scheduled study visit until the end of study (EOS), an average of 2 years)
- (Main cohort: Primary immune thrombocytopenia (ITP)): Percentage of participants with successful IC TPO-RA tapering(From Week 17 Day 1 (W17D1) through Week 33 Day 1 (W33D1).)