A Phase 2, Open-Label, Repeat Dose Study to Assess the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Intravenous ANX005 in Subjects With Warm Autoimmune Hemolytic Anemia (wAIHA)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 5
- 主要终点
- Change in disease activity biomarkers
研究概览
简要总结
This study will evaluate the safety and tolerability of ANX005 in participants with Warm Autoimmune Hemolytic Anemia (wAIHA).
详细描述
After being informed of study details and potential risks, all participants who provide written informed consent will undergo an up to 6-week screening period to determine eligibility. Participants who meet the eligibility criteria will receive two once-weekly intravenous (IV) infusions of ANX005. Participants will return to the clinic weekly through Week 10 for study assessments. The total duration of individual participation in this study will be up to 16 weeks.
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
- •Male or non-pregnant, non-lactating female ≥18 years of age (no maximum age).
- •Diagnosis of wAIHA at least 3 months prior to screening with a direct antiglobulin test (DAT) ≥1 positive for immunoglobulin G (IgG)±C3, or a diagnosis of mixed autoimmune hemolytic anemia (AIHA) that is DAT positive for both IgG and C3, with a presence of a cold antibody with a thermal amplitude ≥30ºCelcius.
- •Hemoglobin (Hgb) level ≤10.0 grams/deciliter (pre-transfusion).
- •Evidence of classical complement pathway activation.
- •Evidence of active hemolysis.
- •Stable use of glucocorticoids and immunosuppressants are permitted.
- •Vaccinations against encapsulated bacterial organisms within 5 years prior to screening or participant must be willing to receive prophylaxis against infections with encapsulated bacteria via vaccination and/or the use of prophylactic antibiotics in accordance with local standards of practice and/or guidelines.
排除标准
- •Elevated aspartate aminotransferase or alanine aminotransferase levels >2.5 times the upper limit of normal.
- •Platelet count <30 X 10^9/liter.
- •History of cold agglutinin disease.
- •History of solid organ, bone marrow, or stem cell transplantation.
- •History of splenectomy within the 3 months prior to screening.
- •Received rituximab or other anti-CD20 monoclonal antibody <3 months prior to screening.
- •Intravenous immunoglobulin (IVIg) treatment within 3 months prior to screening or plasmapheresis or immunoadsorption treatment within 60 days prior to screening.
- •Clinically significant, recent, or ongoing illness or medical condition, including coexistent autoimmune disorder, malignancy, HIV, hepatitis B virus, and hepatitis C virus.
- •History of meningitis or septicemia within the past 2 years.
- •Treatment with an investigational therapeutic agent within 30 days prior to screening.
- •Hypersensitivity to any drug product or excipients used in this study or to previous IV medication administration.
- •Body weight less than 50 kilograms (kg) or greater than 100 kg
研究组 & 干预措施
ANX005
Participants will receive two once-weekly doses of ANX005 at specific time points
干预措施: ANX005 (Drug)
结局指标
主要结局
Change in disease activity biomarkers
时间窗: Baseline to Day 71
Change in hemoglobin, lactate dehydrogenase, bilirubin, reticulocyte count and haptoglobin from baseline
Safety: Treatment-emergent adverse events (TEAEs)
时间窗: Up to Week 16
Number of participants with TEAEs, defined as any adverse event with an onset on or after the day of infusion through 16 weeks after the infusion
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: Day 1 through Day 71
An adverse event (AE) was any untoward medical occurrence in a participant who had been administered a pharmaceutical product. An AE did not necessarily have a causal relationship with the product and therefore could be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a pharmaceutical product. An AE could arise with any use, route of administration, formulation, dose (including an overdose), or when used in combination with another pharmaceutical product. A TEAE was an AE with an onset date/time after the first infusion of ANX005 until the end of the study. A summary of serious and all other non-serious adverse events regardless of causality is located in the Adverse Events module.
Maximum Change From Baseline in Hemoglobin Levels
时间窗: Baseline up to Day 71
Maximum change from Baseline was calculated as the maximum post-Baseline value observed up to Day 71 minus the Baseline value. Baseline was defined as the last non-missing observation recorded before the first dose of ANX005.
Change From Baseline in Lactate Dehydrogenase Levels at Day 71
时间窗: Baseline, Day 71
Change from Baseline was calculated as the post-Baseline value at Day 71 minus the Baseline value. Baseline was defined as the last non-missing observation recorded before the first dose of ANX005.
Change From Baseline in Percentage of Reticulocytes/Total Cells Count at Day 71
时间窗: Baseline, Day 71
Change from Baseline was calculated as the post-Baseline value at Day 71 minus the Baseline value. Baseline was defined as the last non-missing observation recorded before the first dose of ANX005.
Change From Baseline in Haptoglobin Levels at Day 71
时间窗: Baseline, Day 71
Change from Baseline was calculated as the post-Baseline value at Day 71 minus the Baseline value. Baseline was defined as the last non-missing observation recorded before the first dose of ANX005.
Change From Baseline in Total Bilirubin Levels at Day 71
时间窗: Baseline, Day 71
Change from Baseline was calculated as the post-Baseline value at Day 71 minus the Baseline value. Baseline was defined as the last non-missing observation recorded before the first dose of ANX005.
Change From Baseline in Indirect Bilirubin Levels at Day 71
时间窗: Baseline, Day 71
Change from Baseline was calculated as the post-Baseline value at Day 71 minus the Baseline value. Baseline was defined as the last non-missing observation recorded before the first dose of ANX005.
次要结局
- Plasma concentrations(Up to Day 71)
- Change in complement system biomarkers(Baseline to Day 71)
- Change in Percent Inhibition Complement CH50 From Baseline Through Day 71(Baseline, Days 2, 4, 8, 15, 22, 29, 36, 43, 50, 57, and 71)
- Change From Baseline in Complement C4 Level Through Day 71(Baseline, Days 2, 4, 8 (pre-dose and end of infusion), 15, 22, 29, 36, 43, 50, 57, and 71)
- Change From Baseline in Complement C1q Level Through Day 71(Baseline, Days 2 (4 hours [hr] after Infusion and end of infusion), 4, 8 (pre-dose, 4 hr after Infusion, and end of infusion), 15, 22, 29, 36, 43, 50, 57, and 71)