A Phase IV Multicenter, Open-Label Study Evaluating B Cell Levels In Infants Of Lactating Women With CIS Or MS Receiving Ocrelizumab
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 15
- 主要终点
- Percentage of Infants With B Cell Levels (Cluster of Differentiation 19 [CD19+] Cells) Below the Lower Limit of Normal (LLN) Measured at Day 30 After the Mother's First Ocrelizumab Postpartum Infusion
研究概览
简要总结
This study will evaluate the pharmacokinetics of ocrelizumab in the breastmilk of lactating women with clinically isolated syndrome (CIS) or multiple sclerosis (MS) [in line with the locally approved indications] treated with ocrelizumab, by assessing the concentration of ocrelizumab in mature breastmilk, as well as the corresponding exposure and pharmacodynamic effects (blood B cell levels) in the infants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Woman is between 18 and 40 years of age at screening
- •Woman is willing to breastfeed for at least 60 days after the first post-partum ocrelizumab infusion (this decision is to be taken prior to and independent from study participation)
- •Woman is willing to provide breastmilk samples
- •Woman has a diagnosis of MS or CIS (in line with the locally approved indications)
- •Woman has delivered a healthy term singleton infant (≥37 weeks gestation)
- •Infant is between 2-24 weeks of age at the time of the mother's first post-partum dose of ocrelizumab
- •For women who received commercial ocrelizumab (OCREVUS) before enrolment: documentation that last exposure to ocrelizumab occurred more than 3 months before the last menstrual period (LMP) and was given at the approved dose of 2 x 300 mg or 1 x 600 mg
- •Woman agrees to use acceptable contraceptive methods during the study
排除标准
- •related to the Mother:
- •Hypersensitivity to ocrelizumab or to any of its excipients
- •Received last dose of ocrelizumab <3 months before the LMP or during pregnancy
- •Active infections (may be included once the infection is treated and is resolved; women with bilateral mastitis infection should not have samples collected until the infection is completely resolved)
- •Prior or current history of primary or secondary immunodeficiency, or woman in an otherwise severely immunocompromised state
- •Known active malignancies, or being actively monitored for recurrence of malignancy
- •History of breast implants, breast augmentation, breast reduction surgery or mastectomy
- •Prior or current history of chronic alcohol abuse or drug abuse
- •Positive screening tests for hepatitis B
- •Treatment with a DMT for CIS or MS during pregnancy and/or first weeks post-partum, with the exception of formulations of interferon-beta, glatiramer acetate or pulsed corticosteroids
- •Treatment with drugs known to transfer to the breastmilk and with established or potential deleterious effects for the infant
- •Treatment with any investigational agent within 6 months or five half-lives of the investigational drug prior to the LMP
- •Exclusion Criteria related to the Infant:
- •>24 weeks of life at the time of the mother's first dose of ocrelizumab
- •Any abnormality that may interfere with breastfeeding or milk absorption
- •Active infection (may be included once the infection resolves)
- •Infant has any other medical condition or abnormality that, in the opinion of the investigator, could compromise the infant's ability to participate in this study, including interference with the interpretation of study results
- •At least one documented brief resolved unexplained event (BRUE), as defined by the 2016 Guidelines of the American Academy of Pediatrics
研究组 & 干预措施
Women with CIS or MS
Lactating women with CIS or MS (in line with the locally approved indications) who decided together with their treating physician to continue on, or start treatment with, OCREVUS (ocrelizumab) post-partum. Women resuming treatment with ocrelizumab post-partum will be included only if the last exposure to ocrelizumab occurred more than 3 months before the last menstrual period to exclude any interference between fetal exposure and exposure via lactation.
干预措施: Ocrelizumab (Drug)
结局指标
主要结局
Percentage of Infants With B Cell Levels (Cluster of Differentiation 19 [CD19+] Cells) Below the Lower Limit of Normal (LLN) Measured at Day 30 After the Mother's First Ocrelizumab Postpartum Infusion
时间窗: At Day 30
Infant blood samples were collected at Day 30 after the mothers received their first postpartum ocrelizumab infusion (regardless of whether women receive a 600 mg or a 2x300 mg dose). The percentage of infants with B cell levels below LLN are reported with the two-sided Clopper Pearson 95% confidence interval (CI). B-cell reference ranges by week of life (absolute and percentage counts) are defined by Borriello et al. 2022.
Estimated Average Oral Daily Infant Dosage (ADID)
时间窗: Up to Day 60
ADID was calculated as the arithmetic mean of the mother's daily ocrelizumab milk concentration (micrograms/milliliters \[µg/mL\]) over 60 days post-ocrelizumab infusion 1 multiplied by an estimated infant milk intake of 150 milliliters/kilograms/day (mL/kg/day) and based on the weight \[kilograms (kg)\] recorded at the Day 30 visit. Ocrelizumab concentrations reported as below the lower limit of quantification \[LLQ=160 nanograms/millilitres (ng/mL)\] are imputed to zero for the calculation ADID.
次要结局
- Area Under the Milk Concentration-Time Curve (AUC) of Ocrelizumab in Mature Breastmilk(One 600 mg infusion: before infusion and at 24 hours (Day 1), Days 7, 30 and 60 post-infusion; Two 300 mg infusions: before infusion 1 and at 24 hours (Day 1), Days 7, 14, 15 (24 hours after infusion 2), 21, 30 and 60 post-infusion 1)
- Absolute CD19+ B Cell Count in the Infant(At Day 30)
- Percentage of CD19+ B Cell in the Infant(At Day 30)
- Average Concentration of Ocrelizumab in Breastmilk (Cmean)(One 600 mg infusion: before infusion and at 24 hours (Day 1), Days 7, 30 and 60 post-infusion; Two 300 mg infusions: before infusion 1 and at 24 hours (Day 1), Days 7, 14, 15 (24 hours after infusion 2), 21, 30 and 60 post-infusion 1)
- Maximum Concentration (Cmax) of Ocrelizumab in Breastmilk(One 600 mg infusion: before infusion and at 24 hours (Day 1), Days 7, 30 and 60 post-infusion; Two 300 mg infusions: before infusion 1 and at 24 hours (Day 1), Days 7, 14, 15 (24 hours after infusion 2), 21, 30 and 60 post-infusion 1)
- Time of Maximum Concentration (Tmax) of Ocrelizumab in Breastmilk(One 600 mg infusion: before infusion and at 24 hours (Day 1), Days 7, 30 and 60 post-infusion; Two 300 mg infusions: before infusion 1 and at 24 hours (Day 1), Days 7, 14, 15 (24 hours after infusion 2), 21, 30 and 60 post-infusion 1)
- Estimated Maximum Oral Daily Infant Dosage (MDID)(Up to Day 60)
- Average Relative Infant Dose (RID)(Up to Day 60)
- Serum Concentration of Ocrelizumab in the Infant at Day 30(At Day 30)
- Mean Titers of Mumps, IgG Antibody in Response to MMR Vaccination(Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13))
- Mean Titers of Rubella, IgG Antibody in Response to MMR Vaccination(Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13))
- Percentage of Infants With Positive Humoral Response to MMR Vaccination(Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13))
- Mean Titers of Corynebacterium Diphtheriae, IgG Antibody in Response to Diphtheria-Tetanus-Pertussis (DTP) Vaccine(Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13))
- Mean Titers of Bordetella Pertussis, IgG Antibody in Response to DTP Vaccine(Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13))
- Mean Titers of Tetanus Toxoid, IgG Antibody in Response to DTP Vaccine(Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13))
- Percentage of Infants With Positive Humoral Response to DTP Vaccine(Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13))
- Mean Titers of Haemophilus Influenzae Type B (Hib), IgG Antibody in Response to Hib Vaccine(Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13))
- Percentage of Infants With Positive Humoral Response to Hib Vaccine(Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13))
- Mean Titers of Anti-Hepatitis B Surface Antibody in Response to Hepatitis B Virus (HBV) Vaccine(Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13))
- Percentage of Infants With Positive Humoral Response to HBV Vaccine(Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13))
- Mean Titers of Pneumococcal Capsular Polysaccharide, Serotypes, IgG Antibody in Response to 13-valent Pneumococcal Conjugate Vaccine (PCV-13)(Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13))
- Percentage of Infants With Positive Humoral Response to PCV-13(Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13))
- Percentage of Mothers With Adverse Events (AEs)(Up to approximately 73.3 weeks after first ocrelizumab dose)
- Percentage of Infants With AEs(Up to approximately 73.3 weeks after first ocrelizumab dose administered to mother)
- Mean Titers of Measles, Immunoglobin G (IgG) Antibody in Response to Measles, Mumps, and Rubella (MMR) Vaccination(Up to 1 month after the first or second dose of MMR vaccine (at approximately Month 13))