Open-label, Multicenter, International Study of the Efficacy and Safety of the Drug Rhesoglobin (Human Anti-D (rh) Immunoglobulin) Manufactured by Biopharma Plasma LLC, Ukraine, in Pregnant Women in the Antenatal and Postnatal Period in Routine Clinical Practice for the Prevention of Rh Sensitization, With a Subgroup for Evaluation of Some Pharmacokinetic Parameters
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 281
- 试验地点
- 16
- 主要终点
- The part of patients with no antibodies to Rh0 (D) antigen
研究概览
简要总结
Rhesus conflict between mother and fetus is due to the different antigenic composition of erythrocytes. During the first pregnancy, sensitization of the mother to fetal erythrocytes rhesus D (RhD) antigens is formed. During the next pregnancy, fetal red blood cells are attacked by the mother's antibodies, and fetal/newborn hemolytic disease develops. The drug Rhesoglobin blocks the interaction of the fetal erythrocytes RhD antigen and the immune system of the mother and prevents the development of Rhesus sensitization.
详细描述
The screening stage The pregnant woman (participant) has to sign an informed consent. After the signed informed consent procedure, the patient is assessed for meeting the inclusion and non-inclusion (exclusion) criteria. Patients who were included in the study are assessed according to additional criteria for inclusion in the "Pharmacokinetics" subgroup.
The clinical stage
According to the study protocol, patients receive two prophylactic doses of the study drug at a dose of 300 mcg - at 28 weeks of gestation and within 72 hours after delivery. Patients receive the second dose only in the case of the birth of an Rh-positive child. Before and after each injection of the drug, blood will be taken to control the level of anti-Rh0 (D) antibodies. In the "Pharmacokinetics" subgroup, additional blood samples will be taken to determine the following pharmacokinetic parameters:
- Serum clearance
- Volume of distribution
- AUC (area under curve)
- Т1/2 (α and β) (half-life time)
- Cmax (maximum/peak serum concentration)
- Tmax (time to reach the maximum serum concentration)
- Kel (elimination rate constant)
The final stage The patient should be monitored for 6 months ± 5 days, after the last injection of the drug, blood samples are taken after 3 and 6 months to assess sensitization to the Rh antigen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Rh-negative women who are not sensitized to Rh0 (D) antigen between the ages of 18 and 45;
- •signed informed patient consent to participate in the study;
- •pregnancy from a Rh-positive man;
- •immunocompetent patients (CD 4+ counts above 200 per μl, HIV negative, or those with the virus particle count of less than 200 per μl or 400000 per ml);
- •body mass index should be within normal limits (> 18.5 kg / m2 and <30.0 kg / m2);
- •patients who have not received blood transfusions and / or medicinal products containing immunoglobulins in the last 6 months, in particular antibodies to Rh0 (D) antigen;
- •persons who do not have acute and chronic cardiovascular, neuroendocrine, kidney, liver diseases, diseases of gastrointestinal tract, respiratory system;
- •the results of physical, instrumental and laboratory examination of patients should be within the norma or deviations should be regarded by the researcher as clinically insignificant;
- •the ability, according to the researcher, to comply with all the requirements of the study protocol.
排除标准
- •sensitization to Rh0 (D) antigen;
- •the absence of reliable anamnestic data on the prevention of Rh incompatibility in previous pregnancy (s) with the birth of a Rh-positive child;
- •selective IgA deficiency in the presence of antibodies against immunoglobulin A (IgA);
- •history of severe allergic reactions to the administration of human blood protein preparations;
- •hypersensitivity reactions to human donor immunoglobulins;
- •severe thrombocytopenia and other hemostatic disorders;
- •life-threatening conditions and / or complications that require intensive care / surgery, the presence of any other bleeding at the time of screening;
- •Rh-negative fetus;
- •any other concomitant decompensated diseases or acute conditions, the presence of which, according to the researcher, can significantly affect the study results;
- •participation in any other clinical trial in the last 3 months and throughout the study.
- •Additional exclusion criteria:
- •Subgroup "Pharmacokinetics" (patients included in the additional study of some pharmacokinetic parameters):
- •any previous disease or intervention that, according to the researcher, may affect the pharmacokinetics of the study drug, in particular, organ and bone marrow transplantation, cancers;
- •presence of HIV, hepatitis B, or C viruses;
- •presence of severe clinical and laboratory manifestations of impaired liver and kidney function
研究组 & 干预措施
Main group
Patients receive two prophylactic doses of the Human Anti-D (rh) immunoglobulin at a dose of 300 mcg - at 28 weeks of gestation and within 72 hours after delivery. Patients receive the second dose only in the case of the birth of an Rh-positive child.
Before and after each injection of the drug, blood will be taken to control the level of anti-Rh0 (D) antibodies. after the last injection of the drug, blood samples are taken after 3 and 6 months to assess sensitization to the Rh antigen.
15 participants from the Main group are formed the "Pharmacokinetics" subgroup for additional blood samples taking, to determine the pharmacokinetic parameters
干预措施: Human Anti-D (rh) immunoglobulin (Drug)
结局指标
主要结局
The part of patients with no antibodies to Rh0 (D) antigen
时间窗: 6 months after the last administration of the drug
The proportion of patients with no antibodies to Rh0 (D) antigen 6 months after the last administration of the drug
次要结局
- Titer of anti-Rh0 (D) antibodies(6 months after delivery)
- The part of patients with no antibodies to Rh0 (D) antigen 3 months after delivery(3 months after the last administration of the drug)
- Proportion of patients who developed adverse events and reactions (AE / AR)(9 months from the first administration of the drug)