A Phase 1 Safety, Tolerability, and Pharmacokinetics & Pharmacodynamics Study of Multiple- Dose BIVV009 in Patients With Chronic Immune Thrombocytopenia (ITP)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 5
- 主要终点
- Number of Participants With Clinical Laboratory Abnormalities
研究概览
简要总结
The purpose of this study is to explore the safety, preliminary clinical benefit, and activity of BIVV009 in patients with chronic immune thrombocytopenia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- 未提供
排除标准
- •Clinically significant medical history or ongoing chronic illness that would jeopardize the safety of the participant or compromise the quality of the data derived from his/her participation in this study
- •Clinically relevant infection of any kind within the preceding month of enrollment
- •History of venous or arterial thrombosis within the preceding year of enrollment
- •Use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or anticoagulants within 1 week of enrollment
- •Clinical diagnosis of systemic lupus erythematosus (SLE) or other active autoimmune disorders associated with anti-nuclear antibodies (ANAs) including those that are medically controlled, at Screening (other than ITP)
- •Secondary immune thrombocytopenia from any cause including lymphoma, chronic lymphocytic leukemia, and drug-induced thrombocytopenia
- •Positive hepatitis panel (including hepatitis B surface antigen and/or hepatitis C virus antibody) prior to or at Screening
- •Positive human immunodeficiency virus (HIV) test result prior to or at Screening
- •Presence of unacceptable side effects or toxicity associated with BIVV009 (including prior hypersensitivity reactions to BIVV009) such that there is an unfavorable risk-benefit assessment for continued treatment with BIVV009 in the opinion of the Investigator and/or Sponsor
- •For participants who have completed the 9-week safety follow-up/washout period and final study visit before entry into Part B, a positive hepatitis panel (including hepatitis B surface antigen and/or hepatitis C virus antibody) prior to or at Screening. Patients who have undergone hepatitis C antiviral therapy may be allowed if they are documented to be negative for hepatitis C virus ribonucleic acid (RNA) on at least 2 occasions separated by at least 3 months (including 1 RNA test at least 6 months after completion of antiviral therapy) and are also negative for hepatitis C virus RNA at Screening
- •Use of prescribed or over-the-counter medications, supplements, vitamins, and/or herbal remedies within 2 weeks before the first dose of BIVV009 in Part B, which in the judgment of the Investigator may adversely affect the participants welfare or the integrity of the study results (excluding hormonal contraception in female participants)
- •If previously treated with rituximab, the last dose of rituximab was administered < 12 weeks before the first dose of BIVV009 in Part B
- •Clinical diagnosis of systemic lupus erythematosus (SLE) or other active autoimmune disorders associated with anti-nuclear antibodies (ANA), including those that are medically controlled, at Screening (other than ITP). Positive ANAs at screening that are not associated with an autoimmune disorder (other than ITP) may be allowed if present for >= 28 days without associated clinically relevant symptoms
研究组 & 干预措施
BIVV009
Participants who weigh less than 75 kilogram (kg) will receive fixed doses of 6.5 grams of BIVV009 intravenous (IV) infusion and participants who weigh 75 kg or more will receive fixed doses of 7.5 grams of BIVV009 every 2 weeks for approximately 21 weeks in Part A (based on time to complete 11 doses of study drug). There will be a 9-week safety follow-up/washout period after administration of the last dose of study drug in Part A. Participants who have been shown to benefit from BIVV009 treatment during Part A, will receive BIVV009 (based on weight) biweekly for up to 52 weeks of BIVV009 after Last Patient In (LPI) in part B.
干预措施: BIVV009 6.5 grams (Drug)
BIVV009
Participants who weigh less than 75 kilogram (kg) will receive fixed doses of 6.5 grams of BIVV009 intravenous (IV) infusion and participants who weigh 75 kg or more will receive fixed doses of 7.5 grams of BIVV009 every 2 weeks for approximately 21 weeks in Part A (based on time to complete 11 doses of study drug). There will be a 9-week safety follow-up/washout period after administration of the last dose of study drug in Part A. Participants who have been shown to benefit from BIVV009 treatment during Part A, will receive BIVV009 (based on weight) biweekly for up to 52 weeks of BIVV009 after Last Patient In (LPI) in part B.
干预措施: BIVV009 7.5 grams (Drug)
结局指标
主要结局
Number of Participants With Clinical Laboratory Abnormalities
时间窗: Approximately 97 weeks
Clinical laboratory abnormalities including one or more specific target-organs for toxicity of BIVV009, abnormalities in D-dimer, thrombin-anti-thrombin assay, and Systemic Lupus Erythematosus (SLE) panel.
Incidence of Treatment-Emergent Adverse Events
时间窗: Up to 97 weeks
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. A serious adverse event (SAE) is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Number of Participants With Premature Study Terminations
时间窗: Approximately 97 weeks
Number of participants with premature study terminations will be assessed.
次要结局
- Part A: Change From Baseline in Peripheral Blood Platelet Count during BIVV009 Treatment(Baseline up to Day 147)
- Part A: Number of Participants who are independent from using combination Immune Thrombocytopenia (ITP) therapy during A-EOT but receive combination ITP therapy after A-EOT(Day 147 (A-EOT) up to Day 196 (EOS))
- Part A: Number of Participants who Achieve Complete Response Through A-EOT(Up to Day 147)
- Part A: Number of Participants who Achieve Response Through A-EOT(Up to Day 147)
- Part A: Change From Baseline in Peripheral Blood Platelet Count at Part A End of Treatment (A-EOT)(Baseline and A-EOT (Day 147))
- Part A: Duration of Complete Response per Each CR(Up to Day 196)
- Part A: Duration of Response per Each Response(Up to Day 196)
- Part A: Time to First Platelet Response(Up to Day 196)
- Part A: Number of Participants who Report Loss of Response Among Those who Achieve Response(Up to Day 196)
- Part A: Number of Participants who Report Loss of Complete Response Among Those who Achieve Complete Response(Up to Day 196)
- Part B: Change From Baseline in Peripheral Blood Platelet Count to B-EOT(Baseline up to 52 weeks)
- Part B: Number of Participants who Achieve CR and the Lack of Platelet Transfusions or Other ITP Therapy During Treatment Period(Up to 52 weeks)
- Part B: Number of Participants who Achieve Response Through Part B End of Treatment (B-EOT)(Up to 52 weeks)
- Part B: Duration of Complete Response per Each CR(Up to 52 weeks)
- Part B: Duration of Response per each Response(Up to 52 weeks)
- Part B: Number of Participants who achieve a platelet count >= 100*10^9/L on 2 consecutive occasions at least 7 days apart and have the absence of bleeding on and through these two visits and use any combination ITP therapy through B-EOT(Up to 52 weeks)
- Part B: Number of Participants who achieve a platelet count >=30*10^9/L, a >2-fold increase from baseline measured on 2 consecutive occasions at least 7 days apart, have absence of bleeding on and through these two visits, use any combination ITP therapy(Up to 52 weeks)
- Part B: Number of Participants who do not Require Other Immune Thrombocytopenia (ITP) Therapy (non-transfusion) During the Part B Treatment Period(Up to 52 weeks)
- Part B: Number of Participants who do not Require Platelet Transfusions During the Part B Treatment Period(Up to 52 weeks)
- Part B: Number of Participants who Experience any Bleeding Episode, Bleeding by Grade or Serious Bleeding(Up to 52 weeks)
- Plasma Concentrations of BIVV009(Approximately 97 weeks)
- Maximum Observed Plasma Concentration (Cmax) of BIVV009(Approximately 97 weeks)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of BIVV009(Approximately 97 weeks)
- Number of Participants With Anti-drug antibodies (ADAs) Against BIVV009(Up to 97 weeks)
- Complement System Classical Pathway Levels as Measured by WIESLAB Assay(Up to 97 weeks)
- Total Complement (CH50) Levels(Up to 97 weeks)
- Area Under the Concentration-time Curve (AUC) From Hour 0 to the last quantifiable time point (AUC [0-t]) of BIVV009(Approximately 97 weeks)
- C1 Complex Components: C1q(Up to 97 weeks)
- Total Complement Factor C4 Levels(Up to 97 weeks)
- Thrombopoietin Level(Up to 97 weeks)