EUCTR2016-002128-10-DE进行中（未招募）1 期
An adaptive Phase I/II study to assess safety, efficacy, pharmacokinetics and pharmacodynamics of RO7112689 in healthy volunteers and patients with paroxysmal nocturnal hemoglobinuria (PNH)
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 49
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •Part 1 (HVs only)
- •- Healthy male volunteers between the age of 21 and 55 years
- •- Neisseria meningitidis vaccination against serogroups B and A, C, W, and Y
- •- Subjects with a negative hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C antibody, and HIV test result are eligible for the study
- •- Subjects who have been vaccinated against hepatitis B
- •- Willing to comply with a non-smoking policy during the in-clinic portion
- •of the study
- •Parts 2, 3 and 4 (PNH patients only)
- •- Male or female patients between the age of 18 and 75 years
- •- Neisseria meningitidis vaccination in accordance with most current local guidelines or Standard of Care (SOC) for patients at increased risk
- •for meningococcal disease (Part 2 and Part 4 Arm A)
- •- Patient has been vaccinated with Neisseria meningitidis vaccine(s) in accordance with most current local guidelines or SOC for patients at
- •increased risk for meningococcal disease or is being revaccinated if applicable (Part 3 and Part 4 Arm B)
- •- Stable dose for >= 28 days prior to screening of other therapies (immunosuppressant therapy, corticosteroids, iron supplements)
- •- Negative pregnancy test for women of childbearing potential Part 2 and Part 4 Arm A only (currently untreated PNH patients who are
- •candidates for treatment with complement inhibitors only):
- •- Hepatitis B patients can be enrolled if their LFT values are less than 2 × ULN and there is no liver function impairment
- •- PNH patients who have not been treated with any complement inhibitor or if previously treated stopped treatment due to lack of efficacy based on a single missense C5 heterozygous mutation Part 3 and Part 4 Arm B only (PNH patients currently treated with eculizumab only):
- •- Subjects with a negative hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C antibody, and HIV test result are eligible for the study.
- •o Subjects seropositive for HCV but adequately treated without detectable HCV RNA are eligible
- •o Subjects who have been vaccinated against hepatitis B are eligible
- •o Subjects seropositive for HBV but adequately treated without detectable HBV DNA are eligible
- •- Patients are adequately controlled based on investigator opinion
- •- Patients receive regular infusions of eculizumab OLE only - PNH patients:
- •- PNH patients who have completed Parts 2, 3 and 4 respectively
- •- PNH patients who derived, in the Investigator's opinion, benefit from treatment with crovalimab
- •- For women who are not post menopausal and have not undergone surgical sterilization agreement to remain abstinent or use a contraception method that results in a failure rate of <1% per year, during the treatment period and for 5.5 half-lives or at least t 10.5 months after the last dose of crovalimab
- •- Vaccination currency for Neisseria meningitidis serotypes A, C, W, Y and B should be maintained throughout the OLE, according to local guidelines or SOC as applicable in patients with complement deficiency.
- •In the absence of clear local guidelines for Neisseria meningitidis, the Advisory Committee on Immunization Practices (ACIP) 2020 Guidelines are recommended
- •Are the trial subjects under 18? no
- •Number of subjects for this age range:
- •F.1.2 Adults (18-64 years) yes
- •F.1.2.1 Number of subjects for this age range 40
- •F.1.3 Elderly (>=65 years) yes
- •F.1.3.1 Number of subjects for this age range 9
排除标准
- •Parts 1, 2, 3 and 4:
- •- Known or suspected hereditary complement deficiency
- •- History of meningococcal meningitis
- •- Any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 28 days prior to screening or oral antibiotics within 2 weeks prior to screening and up to first study drug administration
- •- History of or currently active primary or secondary immunodeficiency, including known history of HIV infection
- •- Evidence of malignant disease including myelodysplastic syndrome, or malignancies diagnosed within the previous 5 years
- •- Pregnant or breastfeeding, or intending to become pregnant during the study, including the OLE period, within 46 weeks (approximately 10.5 months) after the final dose of crovalimab
- •Part 1 (HVs only):
- •- Any clinically relevant history or the presence of moderate to severe respiratory, renal, hepatic, gastrointestinal, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, or connective tissue disease
- •- Any major illness within one month before the screening examination or any febrile illness within 2 weeks prior to screening and up to first study drug Administration
- •- Prior splenectomy
- •- History or presence of clinically significant electrocardiogram (ECG) abnormalities or cardiovascular disease
- •- Congenital or acquired complement deficiency
- •- Carriers of Neisseria meningitidis based on cultures from naso-pharyngeal swabs
- •Parts 2, 3 and 4 (PNH patients only):
- •- Evidence of moderate to severe concurrent renal, liver, cardiac, pulmonary or gastrointestinal disease not related to PNH as determined by the Investigator
- •- History of bone marrow transplantation
- •- Treatment with azathioprine or erythrocyte-stimulating agents within 14 days prior to first study drug Administration
- •- Splenectomy < 1 year before start of crovalimab.
- •Part 3 and 4 Arm B ( PNH patients only):
- •- Any evidence of sero-positive auto-immune connective tissue
- •- Any evidence of active inflammatory conditions
研究者
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