A phase 3 randomized, double-blind study of ianalumab (VAY736) versus placebo in addition to eltrombopag in patients with primary immune thrombocytopenia (ITP) who had insufficient response or relapsed after first line steroid treatment (VAYHIT2)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 35
- 主要终点
- Time to treatment failure (TTF) defined as the time from randomization until: - Platelet counts <30 G/L or need for rescue treatment later than 8 weeks from randomization, - Start of new ITP treatment - Ineligibility to taper or inability to discontinue eltrombopag or - Death. TTF will be assessed in each treatment group and each of the 2 doses of ianalumab (ianalumab+ eltrombopag) will be compared to the control arm (placebo+ eltrombopag).
研究概览
简要总结
To demonstrate that the addition of ianalumab (either dose) to standard of care, eltrombopag, prolongs Time to Treatment Failure (TTF) compared to eltrombopag alone in participants with primary ITP who have had an insufficient response to or relapsed after first-line treatment with corticosteroids
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Male or female patients aged 18 years and older on the day of signing the informed consent.
- •A signed informed consent must be obtained prior to participation in the study
- •A diagnosis of primary ITP, with insufficient response to, or relapse after a first-line corticosteroid therapy ± IVIG.
- •Patients with platelet count <30 G/L for whom eltrombopag is clinically indicated as per physician’s discretion and with no contraindication to receive eltrombopag.
排除标准
- •ITP patients who received second-line ITP treatments (other than corticosteroid therapy ± IVIG) including splenectomy. However, patients exposed to thrombopoietin receptor agonist (TPO-RAs) for a limited time (max. one week) before screening are eligible.
- •Patients with key lab abnormalities and patients with Evans syndrome or any other cytopenia (patients with low grade anemia related to bleeding or iron deficiency are eligible).
- •Patients with history of clinically significant hematological disorders, or with marked altered hematologic parameters.
- •Patients with current or history of life-treating bleeding.
- •Patients that are Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), Hepatitis B surface Antigen (HBsAg)/ Hepatitis B core antibody (HBcAb)- positive.
- •Patients with known active or uncontrolled infection requiring systemic treatment during screening period.
- •Patients with hepatic impairment with Child-Pugh score >5
- •Patients with concurrent coagulation disorder and/or receiving anti-platelet or anticoagulant medication with an exemption of low dose of acetylsalicylic acid (≤150 mg daily).
- •Nursing (breast feeding) or pregnant women.
研究组 & 干预措施
ELTROMBOPAG, ELTROMBOPAG, ELTROMBOPAG, ELTROMBOPAG
干预措施: ELTROMBOPAG (Drug)
Placebo to ianalumab 150 mg/1 mL concentrate for solution for infusion
干预措施: Placebo to ianalumab 150 mg/1 mL concentrate for solution for infusion (Drug)
VAY736
干预措施: VAY736 (Drug)
结局指标
主要结局
Time to treatment failure (TTF) defined as the time from randomization until: - Platelet counts <30 G/L or need for rescue treatment later than 8 weeks from randomization, - Start of new ITP treatment - Ineligibility to taper or inability to discontinue eltrombopag or - Death. TTF will be assessed in each treatment group and each of the 2 doses of ianalumab (ianalumab+ eltrombopag) will be compared to the control arm (placebo+ eltrombopag).
Time to treatment failure (TTF) defined as the time from randomization until: - Platelet counts <30 G/L or need for rescue treatment later than 8 weeks from randomization, - Start of new ITP treatment - Ineligibility to taper or inability to discontinue eltrombopag or - Death. TTF will be assessed in each treatment group and each of the 2 doses of ianalumab (ianalumab+ eltrombopag) will be compared to the control arm (placebo+ eltrombopag).
次要结局
- Number and proportion of participants receiving rescue treatment.
- At each time point: - Complete Response (CR) rate (proportion of participants with any platelet count ≤100 G/L without rescue or new ITP treatment).Response rate (R) (proportion of participants with any platelet count ≤50 G/L without rescue or new ITP treatment). Best response rate over all time points(proportion of participants with a best response of either R or CR). Time from randomization to R & CR. Duration of R & CR. Stable response at 6 months & at 1 year.
- Probability to be treatment failure-free (as defined for the primary efficacy endpoint) at the end of the planned treatment period (end of Week 24)
- Frequency of adverse events and other safety parameters. Number of severe infections and proportion of participants with severe infection.
- Proportion of participants with bleeding events according to World Health Organization (WHO)Bleeding Scale.
- Change from baseline on total score of the Patient- Reported Outcomes Measurement Information System (PROMIS)Short Form (SF) v1.0 Fatigue 13a. Change from baseline in ITP Patient Assessment Questionnaire (PAQ) domain scores of Symptoms, Fatigue, Bother, Activity.
- B-cell levels: - Change from baseline in the frequency (% within the CD45) and absolute number of CD19+ B-cell counts - Time to first occurrence of B-cell recovery, defined as ≥80% of baseline or ≥50 cells/µL Immunoglobulins: - Change from baseline in immunoglobulin level
- Ianalumab concentration in serum and PK parameters after the first and last dose in a subset of participants
- Incidence and titer of anti-ianalumab antibodies in serum (anti-drug antibodies (ADA) assay) over time
研究者
Novartis Pharma Arzneimittel GmbH
Scientific
Novartis Pharma AG