A Phase 3, Randomized, Double-blind, Study to Assess Efficacy and Safety of Ianalumab (VAY736) Versus Placebo in Warm Autoimmune Hemolytic Anemia (wAIHA) Patients Who Failed at Least One Line of Treatment
概览
- 阶段
- 3 期
- 干预措施
- Ianalumab
- 疾病 / 适应症
- Warm Autoimmune Hemolytic Anemia (wAIHA)
- 发起方
- Novartis Pharmaceuticals
- 入组人数
- 90
- 试验地点
- 54
- 主要终点
- Binary variable indicating whether a patient achieves a durable response
- 状态
- 进行中（未招募）
- 最后更新
- 上个月
概览
简要总结
The purpose of this study is to evaluate efficacy and safety of ianalumab compared to placebo in patients with warm autoimmune hemolytic anemia, who failed at least one line of treatment.
详细描述
The primary objective is to demonstrate that either dose of ianalumab induces a durable hemoglobin response compared to placebo in patients with wAIHA. The key secondary objective is to demonstrate that either dose of ianalumab maintains a durable hemoglobin response that is sustained beyond end of the treatment period, compared to placebo. Participants are randomized to two different doses of ianalumab or placebo. Participants who were assigned to placebo arm and not responding to treatment may be treated with open label ianalumab using the higher dose. The investigational treatment will be supplied in a double-blinded manner. For the open label period, ianalumab will be provided in an open label manner. In addition to the randomized treatment (ianalumab or placebo), specific supportive care medication as defined in the protocol is allowed. If clinically indicated (e.g., to ensure patient safety), the treating physician may also administer rescue medication. The study consists of the treatment period, efficacy and safety follow-up periods. The visit frequency will be every other week during the treatment and primary endpoint follow up period; for safety monitoring monthly during the first 20 weeks after last dose and afterwards quarterly up to 2 years from the last dose. For participants in durable response, additional visits for efficacy will occur monthly during the first 2 years after the last dose, and afterwards quarterly until loss of response or end of study, latest until up to 39 months post randomization of the last participant.
研究者
入排标准
入选标准
- •18 years and older at time of signing consent
- •Patients with primary or secondary wAIHA documented by positive direct antiglobulin test specific for anti-IgG or anti-IgA, who had an insufficient response to, or relapsed after at least one line of treatment, including patients with steroid resistance, dependence or intolerance
- •Hemoglobin concentration at screening and at Week 1 \>=5 g/dL and \<10 g/dL, associated with presence of symptoms related to anemia
- •The dose of supportive care must be stable for at least 4 weeks prior to randomization into the study
排除标准
- •wAIHA secondary to hematologic disease involving bone marrow (e.g., CLL) or another immunologic disease requiring prohibited medication as per protocol. Patients with autoimmune diseases after wash-out from the treatments are allowed.
- •Presence of other forms of AIHA (cold or intermediate forms), Evans Syndrome or other cytopenias
- •Prior use of B-cell depleting therapy (e.g., rituximab) within 12 weeks prior to randomization, or without hematological response to the last course of B-cell depleting therapy
- •Neutrophils: \<1000/mm3
- •Serum creatinine \>1.5 × upper limit of normal (ULN)
- •Immunoglobulin G (IgG) \<5g/L
- •Active viral, bacterial or other infections (including tuberculosis and SARS-CoV-2) requiring systemic treatment at time of screening, or history of recurrent clinically significant infection
- •Positivity for hepatitis C virus, hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb). HBcAb positive patients can be enrolled if HBsAg negative, HBV DNA negative, no pre-existing liver fibrosis is present and antiviral prophylaxis is given.
- •Known history of primary or secondary immunodeficiency, or a positive human immune deficiency virus (HIV) test result
- •Live or live-attenuated vaccination within 4 weeks before randomization
研究组 & 干预措施
Ianalumab low dose
Participants will receive low dose ianalumab intravenously
干预措施: Ianalumab
Ianalumab high dose
Participants will receive high dose ianalumab intravenously
干预措施: Ianalumab
Placebo
Participants will receive placebo intravenously
干预措施: Placebo
结局指标
主要结局
Binary variable indicating whether a patient achieves a durable response
时间窗: Randomization to Week 25
Durable response: hemoglobin level ≥10 g/dL and ≥2 g/dL increase from baseline, for a period of at least eight consecutive weeks between W9 and W25, in the absence of rescue medication or prohibited treatment
次要结局
- Response rate(Randomization to end of study (up to 39 months after randomization of last patient))
- Time from randomization to start of durable response in each treatment group(Randomization to end of study (up to 39 months after randomization of last patient))
- Complete response rate(Randomization to end of study (up to 39 months after randomization of last patient))
- Change from baseline in immunoglobulin levels(Randomization until month 30)
- Ianalumab PK parameter - AUClast(After first dose of study treatment (pre-dose, 2 hours, 336 hours, 672 hours post dose) and after last dose (pre-dose, 2 hours, 336 hours, 672 hours, 1344 hours, 2016 hours and 3360 hours post dose).)
- Immunogenicity of ianalumab(Randomization to end of study (up to 39 months after randomization of last patient))
- Time from randomization to start of complete response in each treatment group(Randomization to end of study (up to 39 months after randomization of last patient))
- Number of participants who received rescue treatment (overall & by type of rescue treatment)(Randomization to end of study (up to 39 months after randomization of last patient))
- Duration of response (Key Secondary)(Randomization to end of study (up to 39 months after randomization of last patient))
- Hemoglobine Levels(Randomization to end of study (up to 39 months after randomization of last patient))
- Change from baseline in the the frequency and 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, defined as ≥80% of baseline or ≥50 cells/μL(Randomization to end of study (up to 39 months after randomization of last patient))
- Ianalumab PK parameter - Tmax(After first dose of study treatment (pre-dose, 2 hours, 336 hours, 672 hours post dose) and after last dose (pre-dose, 2 hours, 336 hours, 672 hours, 1344 hours, 2016 hours and 3360 hours post dose).)
- Time from randomization to start of first response in each treatment group(Randomization to end of study (up to 39 months after randomization of last patient))
- Ianalumab PK parameter - Cmax(After first dose of study treatment (pre-dose, 2 hours, 336 hours, 672 hours post dose) and after last dose (pre-dose, 2 hours, 336 hours, 672 hours, 1344 hours, 2016 hours and 3360 hours post dose).)
- Percentage of participants who received rescue treatment (overall & by type of rescue treatment)(Randomization to end of study (up to 39 months after randomization of last patient))
- Change from baseline in the T-score of PROMIS Fatigue-13a questionnaire(Randomization to end of study (up to 39 months after randomization of last patient))
- Ianalumab PK parameter - Accumulation ratio Racc(After last dose (pre-dose, 2 hours, 336 hours, 672 hours, 1344 hours, 2016 hours and 3360 hours post dose).)
- Change from baseline in the 8 domain scores and in the summary scores (PCS, MCS) of SF-36 questionnaire(Randomization to end of study (up to 39 months after randomization of last patient))
- Ianalumab PK parameter - AUCtau(After first dose of study treatment (pre-dose, 2 hours, 336 hours, 672 hours post dose) and after last dose (pre-dose, 2 hours, 336 hours, 672 hours, 1344 hours, 2016 hours and 3360 hours post dose).)