Efficacy, Safety, and Pharmacokinetics of Shu Yang IVIG in Patients With Primary Immunodeficiency
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 50
- 主要终点
- Primary Efficacy Objective (average of acute serious bacterial infections)
研究概览
简要总结
To evaluate the safety, efficacy, and pharmacokinetic properties of Shu Yang intravenous immune globulin in patients with primary immune deficiency aged less than 60 years.
The main benefit of IVIG is to help the body fight against a large variety of infections generally associated with morbidity and mortality in patients with primary immunodeficiency diseases, particularly in CVID and XLA. In addition, a decrease in the number of infections, a reduction in medications and hospitalizations, and a better quality of life are expected.
Throughout treatment, approximately one-fourth of persons may experience a side effect. These are usually mild or bothersome but not dangerous. Very rarely, more serious side effects like allergic reactions or low blood counts (anemia) can occur. One of the most common side effects is headache. Other side effects include chills, fever, flushing, flu-like muscle pains or joint pains, feeling tired, nausea, vomiting, and rash. For the most part, these reactions typically happen with the first dose of IVIG or because change to a different brand of IVIG. All IVIG products have similar warnings and contraindications, such as the potential for renal failure, thrombotic events, aseptic meningitis, hemolysis, and anaphylactic reactions.
详细描述
This is a Phase III, open-label, prospective, single-arm, multicenter trial to evaluate the efficacy of IVIG in maintaining the average of severe bacterial infections in less than one per year. The safety and pharmacokinetics (PK) of the investigational product will also be evaluated. Fifty male or female patients aged up to 60 years old will be selected. At least 20 patients must be up to 17 years old. During the trial, at least 20 adult patients will be invited to make up the PK assessment subgroups.
After obtaining the signed Informed Consent/Assent Form , the screening procedures will be performed including the immune deficiency history from the medical records and safety exams. Patients will start the trial with a run-in period to stabilize the IgG trough levels. This period could last two to six visits with posological adjustments until the last two IgG trough levels are above 4 (5) g/L.
After the run-in, the one-year test period will start at the V0. Depending on the treatment regimen, the patients will receive IVIG every 21 days (±3 days) up to day 378 or every 28 days (±4 days) up to day 364 when the close-out visit will occur. In all visits from all patients, a blood sample will be collected immediately before each IVIG administration to assess the IgG trough levels.
To assess the investigational product PK properties, a group of 20 patients will collect additional blood samples for dosing IgG levels between Visit 4 and Visit 5. Those taking IVIG every 21 days, will collect six additional blood samples at the following times after the injection 30 min, 2h, 24h, 72h, 7 days, and 14 days. Those taking IVIG every 28 days will collect seven additional blood samples at the times 30 min, 2h, 24h, 72h, 7 days, 14 days, and 21 days.
Adverse events will be collected at all visits to fulfill the safety endpoints. Moreover, the patients will have continuous access to the investigator's team to report adverse events, be instructed about how to proceed, or even perform Extra visits for presential medical evaluation.
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
盲法说明
The trial will be open-label and single-arm. Therefore, there will be no randomization or blinding.
入排标准
- 年龄范围
- 6 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent/assent.
- •Male or female.
- •Ages ≤ 60 years old and ≥ 06 years old.
- •Diagnosis of Primary Immunodeficiency Disease (PID) with a reduction in antibody production due to:
- •a. Common Variable Immunodeficiency (CVID) as per European Immunodeficiency Society (ESID)/Pan American Immunodeficiency Group (PAGID), as defined in section 5.1, OR b. X-linked agammaglobulinemia (XLA) as per ESID/PAGID, as defined in section 5.
- •Receiving replacement therapy with intravenous immunoglobulin at 21- to 28-day intervals at 300-600 mg/kg/month for a minimum of 2 months before the start of the study;
- •Absence of episodes of serious bacterial infections with previous use of an IV immunoglobulin for at least 3 months before screening;
- •Negative pregnancy test (in female patients with childbearing potential); readiness to use reliable methods of contraception throughout the study period;
- •Patients who participated in a clinical trial with another experimental IVIG may be enrolled if they have a potential benefit according to Res. CNS 251/1997;
- •Patients currently on treatment with any subcutaneous or intramuscular immunoglobulin may be enrolled switching to IVIG therapy at the investigator's discretion, considering the potential benefit to the patient.
排除标准
- •Known intolerance or hypersensitivity to immunoglobulins or components of the test article;
- •Any contraindications to the use of immunoglobulins;
- •Secondary immunodeficiency or conditions potentially causing secondary immunodeficiency such as chronic lymphoid leukemia, lymphoma, multiple myeloma, protein-losing enteropathies or nephropathies, and hypoalbuminemia;
- •Clinically relevant changes in the safety exams are defined as:
- •Blood count
- •o Hb < 10.5 g/dL
- •o Leukocytes < 3,000 /uL or >10,000 cells / uL
- •o Absolute neutrophil count < 1,000 cells/mm3;
- •Coagulation o TP and aPTT > 2.5 x ULN
- •Biochemistry o glycated hemoglobin > 6.5%
- •total bilirubin and fractions, alkaline phosphatase, ALT, AST, GGT > 2.5 x ULN
- •creatinine above 3mg/dl or creatinine clearance < 30mL/min
- •Leukocyturia > 10,000 cells/mL
- •Any cancer either active or resolved within the last 12 months before screening;
- •Receiving any blood products (except intravenous immunoglobulins) during the last 3 months before screening;
- •Any febrile illness within 14 days before enrollment; Note: The patient may be rescreened after recovery.
- •History of thrombotic events (including myocardial infarction, stroke, pulmonary embolism, and deep vein thrombosis) within 6 months before enrollment;
- •Previous use of live attenuated virus vaccines;
- •Selective deficiency of immunoglobulin A (IgA) or known antibodies to IgA;
- •Known drug or alcohol abuse;
- •The need to use other investigational drugs, systemic immunosuppressants, and any other immunoglobulins;
- •Pregnancy or lactation;
- •Inability to comply with the protocol activities;
- •PIDs other than CVID or X-linked agammaglobulinemia
- •Patients infected with HIV, HBV or HCV
- •Patients with AIDS, cystic fibrosis, or active hepatitis B or C.
- •Any other condition that, in the Investigator's opinion may increase the risk of participation in this study.
结局指标
主要结局
Primary Efficacy Objective (average of acute serious bacterial infections)
时间窗: Between Visit 0 and Final Visit (through study completion, an average of 1 year)
The incidence of serious bacterial infections (septicemia, meningitis, visceral abscess, osteomyelitis, and pneumonia) within the 1-year follow-up is less than 1.0 per patient/year in the average of the population.
次要结局
- Secondary Efficacy Objectives (assessment of the rate of non-serious infections)(Average incidence of non-serious infections per patient between Visit 0 and Final Visit (through study completion, an average of 1 year), as documented as treatment emergent adverse events (TEAEs);)
- Secondary Efficacy Objectives(Number of days hospitalized per month overall and due to infection, as documented as treatment emergent adverse events - TEAEs (through study completion, an average of 1 year).)