NCT05539248招募中1 期
A Multicenter, Open-label, Multiple Ascending Dose Phase 1b/2 Trial to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of CAN106 Intravenously in Subjects With PNH Naïve to Complement-Inhibitor Treatment
CARE Pharma Shanghai Ltd.1 个研究点 分布在 1 个国家目标入组 78 人开始时间: 2022年3月25日最近更新:
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Percent Change In Lactate Dehydrogenase (LDH) Levels Normalization From Baseline to Day 182(Phase 2)
研究概览
简要总结
The purpose of the study is to evaluate the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of CAN106 administered intravenously to subjects with PNH who have not previously been treated with a complement inhibitor.
详细描述
This is an open-label, multiple dose escalation study to assess the safety, tolerability, efficacy, PK, PD and immunogenicity of CAN106 given as an IV infusion. The data presented is up to the primary completion date of the study and is for the 26-week primary evaluation period. The study also includes an extension period of up to 52 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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 female patients ≥18 years of age.
- •Body weight ≥40 kg at screening.
- •Documented diagnosis of PNH within 6 months prior to screening, confirmed by high-sensitivity flow cytometry evaluation of red blood cells (RBCs), with granulocyte or monocyte clone size of ≥10%.
- •LDH level ≥ 1.5 X ULN at screening.
- •Mean hemoglobin(Hb)<10 g/dL for those who have not received blood. transfusion at screening, based on 2 measurements from separate blood samples collected at interval of 2-8 weeks apart prior to the first dosing. Or hemoglobin < 10 g/dL at the first screening and then with subsequent red blood cell transfusions.
- •Presence of 1 or more of the following PNH-related signs or symptoms within 3 months of Screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia (hemoglobin < 10 g/dL), history of a major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction; or history of pRBC transfusion due to PNH.
- •All patients must be vaccinated against meningococcal infections within 3 years prior to, or at the time of, initiating study drug. Patients who initiate study drug treatment less than 2 weeks after receiving a meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination.
- •If available, Haemophilus influenzae type b and Streptococcus pneumoniae vaccines can be administered according to national vaccine guidelines, and antibiotic prophylaxis should be given until 2 weeks after vaccination if the vaccines are administered within 14 days prior to administration.
- •All females of childbearing potential and all males must be willing to use at least one highly effective method of contraception from signing of informed consent until 8 months after the last dose of CAN106 Injection; Male subjects with female partners of childbearing potential must be willing to use condoms in addition to using a highly effective method of contraception.
- •Subjects should be willing to sign the informed consent forms and comply with the study visit.
排除标准
- •Current or previous treatment with a complement inhibitor.
- •Positive pregnancy test on day 1, or female patients who are planning to become pregnant or are pregnant or breastfeeding.
- •Participation in an interventional clinical study within 28 days before initiation of dosing on Day 1, or within 5 half-lives of the investigational product, whichever is greater.
- •Platelet count < 30 × 10^9/L at Screening.
- •Absolute neutrophil count < 0.5 × 10^9/L at Screening.
- •Alanine aminotransferase (ALT) > 3 × ULN, or both direct bilirubin and alkaline phosphatase (ALP) > 2 × ULN during the screening period.
- •Serum creatinine > 2.5 × ULN and creatinine clearance < 30 mL/min as calculated by the Cockcroft-Gault formula during the screening period.
- •History of malignancy within 5 years of Screening with the exception of nonmelanoma skin cancer or carcinoma in situ of the cervix that has been treated with no evidence of recurrence.
- •History of bone marrow transplantation.
- •Major surgery within 90 days prior to screening.
- •History of N. meningitidis infection or unexplained, recurrent infection.
- •Known or suspected hereditary complement deficiency.
- •Active systemic bacterial, viral, or fungal infection within 14 days prior to dosing
- •Presence of fever ≥38°C within 7 days prior to study drug administration.
- •Having received splenectomy within 6 months prior to screening.
- •Known history of severe allergic or anaphylactic reactions to antibiotics and are unwilling to use prophylaxis as specified in the protocol.
- •Patients are excluded if they are taking any of the following medications and are not on a stable regimen(as judged by investigator) for the time period indicated prior to screening:
- •Erythropoietin or immunosuppressants for at least 8 weeks;
- •Corticosteroids for at least 4 weeks;
- •Vitamin K antagonists with a stable international normalized ratio for 4 weeks;
- •Iron supplements or folic acid for at least 4 weeks;
- •Low molecular weight heparin for at least 4 weeks.
- •Known allergy to excipients of CAN106 or allergy to Chinese hamster ovary cell proteins.
- •Immunization with a live-attenuated vaccine 1 month prior to dosing on day
- •Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to the start of Screening.
- •Inability to comply with study requirements.
- •History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease (eg, active hepatitis) that, in the opinion of the Investigator or Sponsor, precludes the patient's participation in an investigational clinical trial.
- •Known medical or psychological condition(s) or risk factor that, in the opinion of the Investigator, might interfere with the patient's full participation in the study, pose any additional risk for the patient, or confound the assessment of the patient or outcome of the study.
研究组 & 干预措施
Dose escalation CAN106 in cohort 1
Experimental
Subjects are administered CAN106 20 mg/kg IV maintenance dosing.
干预措施: CAN106 20 mg/kg (Drug)
Dose escalation CAN106 in cohort 2
Experimental
Subjects are administered CAN106 40 mg/kg IV maintenance dosing.
干预措施: CAN106 40 mg/kg (Drug)
Dose escalation CAN106 in cohort 3
Experimental
Subjects are administered CAN106 80 mg/kg IV maintenance dosing.
干预措施: CAN106 80 mg/kg (Drug)
结局指标
主要结局
Percent Change In Lactate Dehydrogenase (LDH) Levels Normalization From Baseline to Day 182(Phase 2)
时间窗: Baseline, Day 182
Baseline is defined as the average of all available assessments prior to first CAN106 infusion.
Incidence and severity of treatment-emergent adverse events (TEAEs) of multiple doses of CAN106 as assessed by CTCAE v5.(Phase 1b)
时间窗: 182 days
TEAEs were defined as adverse events (AE) that occurred after dosing on Day 1 and up to 28 days after the last dose of CAN106, include adverse events (AEs), serious adverse events (SAEs), AEs of special interest (AESIs), abnormal laboratory data compared with baseline, vital signs, and electrocardiograms (ECGs)
次要结局
- PD parameters-CH50(182 days)
- Maximum Plasma Concentration (Cmax) - Pharmacokinetics parameter(182 days)
- Time to Maximum Concentration (Tmax) - Pharmacokinetics parameter(182 days)
- t1/2 - Pharmacokinetics parameter(182 days)
- PD parameters-free C5(182 days)
- Immunogenicity(182 days)
- Area Under the Curve (AUC) - Pharmacokinetics parameter(182 days)
- Changes from Baseline in Serum Lactate Dehydrogenase (LDH) Level(182 days)
- Percent Change In Free Hemoglobin Level From Baseline to Day 182(182 days)
- Percent Change In Haptoglobin Levels From Baseline to Day 182(182 days)
- PD parameters- total C5(182 days)
- Changes in scores of patient-reported outcomes as measured by European Organization for Research and Treatment of Cancer [EORTC]- Quality of life questionnaire-core 30 (QLQ-30)(182 days)
- Changes in scores of patient-reported outcomes as measured by FACIT-Fatigue from Baseline to Day 182(182 days)
研究者
研究点 (1)
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