PRIMULA Lac (Prospective Registry Investigating Maternal, Infant, and Lactation Outcomes in Anifrolumab Users): The AstraZeneca Lactation Study for Anifrolumab
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Area under the milk concentration-time curve during a dosing interval
研究概览
简要总结
Prospective Registry Investigating Maternal, Infant, and Lactation Outcomes in Anifrolumab Users (PRIMULA Lac) is a Post Marketing Requirements (PMR) study designed to fulfill the FDA post-marketing requirements. The study will collect data about the presence of anifrolumab in human breast milk and serum (maternal and infant) among lactating individuals who are receiving anifrolumab therapeutically via intravenous (IV) or subcutaneous (SC) administration and evaluate exposure and effects on the breastfed infant.
详细描述
PRIMULA Lac is an open-label, open enrollment, post marketing study to assess concentrations of anifrolumab in breast milk and serum in lactating individuals who are receiving anifrolumab therapeutically via intravenous (IV) or subcutaneous (SC) administration, and to evaluate exposure on the breastfed infant. For participants with IV administration of anifrolumab, milk collection will occur at a series of 14 timepoints, 1 pre-dose (spot) and 13 post-dose: Day 1 [0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, 18-24 hours], Day 3 [48 hours, spot], Day 4 (spot), Day 6 (spot), Day 8 (spot), Day 12 (spot), Day 16 (spot), Day 22 (spot), and Day 29 (prior to next dose, spot). Maternal serum will be collected on Day 1 (pre-dose and 0-4 hours post-dose), Day 12, and approximately Day 29 (immediately preceding subsequent dose). Infant serum will be collected on approximately Day 30 following the next dose and after 24 hours of breast feeding. Total duration of participation for each participant with IV administration of anifrolumab will be approximately 1 month.
For participants with SC administration of anifrolumab, the total duration of participation will be approximately 9 days. For these participants, milk collection will occur at a series of 10 timepoints, 1 pre-dose (spot) and 9 post-dose: Day 1 [0-4 hours, 4-8 hours, 8-12 hours, 12-18 hours, 18-24 hours], Day 3 [48 hours, spot], Day 4 (spot), Day 6 (spot), Day 8 (prior to next dose, spot). Maternal serum will be collected on Day 1 (pre-dose and 0-4 hours postdose), and approximately Day 8 (immediately preceding subsequent dose). Infant serum will be collected approximately Day 9 following the next dose and after 24 hours of breastfeeding.
Maternal and infant adverse events (AEs) will be actively collected for the duration of participation in the study for IV and SC administration of anifrolumab.
This is a Post Marketing Requirements (PMR) study designed to fulfill the FDA post-marketing requirements.
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
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •18 years or older
- •Signed informed consent to participate
- •Diagnosis of moderate/severe SLE
- •Ongoing treatment with anifrolumab
- •Has reached or will reach steady state (~85 days postpartum, equivalent to at least 3 consecutive previous IV doses or at least 12 previous SC doses during the post-partum period) with anifrolumab by the time of study Day 1 (pre-dose milk collection)
- •Established lactation in the index post-partum period (breastfeeding or pumping for at least 4 weeks at time of Day 1 visit to ensure mature milk production)
- •Willing to breastfeed or pump regularly during the study period to maintain milk supply and exclusively pump breast milk for the 24-hour period of breast milk collection on Day 1 post IV dose
- •Plans to continue feeding infant breast milk at least throughout the duration of the study and is not weaning
- •Must be exclusively breast milk-feeding their infant (or if not exclusively breast milk-feeding, not providing more than 1 supplemental bottle of formula per day) at the time of enrollment and throughout the study period
- •Agrees to use only lanolin nipple cream during the sampling period
- •Gestational age at delivery ≥32 weeks
- •Birthweight > 10th percentile
- •Weight > 10th percentile at the time of enrollment
排除标准
- •Received any investigational compound or approved biologic or biosimilar within 30 days or 5 half-lives (whichever is longer) prior to enrollment in the study
- •Diagnosis of lupus nephritis in the last 12 months
- •History of breast implants, breast augmentation, or breast reduction surgery that significantly impacts breastfeeding or collection of milk from 1 or both breasts
- •History of malignancy in the last 10 years
- •History of mastectomy
- •Evidence of mastitis or any other significant active infection at Day 1 (pre-dose)
- •1. Any abnormality noted or clinically significant medical condition, including cardiac, pulmonary, and liver disease, glucose instability, or active infection at the time of screening that, in the opinion of the investigator, may make implementation of the protocol or interpretation of the trial difficult or would put the infant participant at risk by participating in the study
研究组 & 干预措施
Anifrolumab (IV administration and SC administration)
For participants with IV administration, milk will be collected at 14 timepoints: 1 pre-dose (spot) and 13 post-dose: Day 1 [0-4, 4-8, 8-12, 12-18, 18-24 hours], Day 3 [48 hours], Day 4 (spot), Day 6 (spot), Day 8 (spot), Day 12 (spot), Day 16 (spot), Day 22 (spot), and Day 29 (prior to next dose, spot). Maternal serum collection: Day 1 (pre-dose and 0-4 hours post-dose), Day 12, and Day 29. Infant serum collection: Day 30 after the next dose and after 24 hours of breastfeeding. Total duration of participation will be 1 month. For participants with SC administration, the total duration of participation will be 9 days. Milk will be collected at 10 timepoints: 1 pre-dose (spot) and 9 post-dose: Day 1 [0-4, 4-8, 8-12, 12-18, 18-24 hours], Day 3 [48 hours], Day 4 (spot), Day 6 (spot), Day 8 (prior to next dose, spot). Maternal serum collection: Day 1 (pre-dose and 0-4 hours postdose), and Day 8. Infant serum collection: Day 9 after the next dose and after 24 hours of breastfeeding.
干预措施: Anifrolumab (Drug)
结局指标
主要结局
Area under the milk concentration-time curve during a dosing interval
时间窗: Approximately 30 days
Area under the milk concentration-time curve during a dosing interval is a component used to assess pharmacokinetic (PK) of anifrolumab in milk of lactating individuals. Milk PK parameters of anifrolumab will be derived using non-compartmental analysis methods and will be determined using the concentration-time data for all evaluable participants included in the PK population
Area under the milk concentration-time curve from time 0 to last quantifiable concentration
时间窗: Approximately 30 days
Area under the milk concentration-time curve from time 0 to last quantifiable concentration is a component used to assess PK of anifrolumab in milk of lactating individuals. Milk PK parameters of anifrolumab will be derived using non-compartmental analysis methods and will be determined using the concentration-time data for all evaluable participants included in the PK population
Average milk concentration at steady state
时间窗: Approximately 30 days
Average milk concentration at steady state is a component used to assess PK of anifrolumab in milk of lactating individuals. It will be calculated dividing "Area under the milk concentration-time curve during a dosing interval" by the dosing interval for anifrolumab
Observed milk concentration at end of dosing interval
时间窗: Approximately 30 days
Observed milk concentration at end of dosing interval is a component used to assess PK of anifrolumab in milk of lactating individuals. Milk PK parameters of anifrolumab will be derived using non-compartmental analysis methods and will be determined using data for all evaluable participants included in the PK population
Maximum observed milk concentration
时间窗: Approximately 30 days
Maximum observed milk concentration is a component used to assess PK of anifrolumab in milk of lactating individuals. Milk PK parameters of anifrolumab will be derived using non-compartmental analysis methods and will be determined using data for all evaluable participants included in the PK population
Time of maximum concentration
时间窗: Approximately 30 days
Time of maximum concentration is a component used to assess PK of anifrolumab in milk of lactating individuals. Milk PK parameters of anifrolumab will be derived using non-compartmental analysis methods and will be determined using data for all evaluable participants included in the PK population
次要结局
- Total amount of drug excreted in milk over 24 hours(Day 1)
- Fraction of dose excreted in milk(Day 1)
- Maternal serum pharmacokinetic (PK) concentrations(Maternal serum will be collected Day 1 (pre-dose and 0-4 hours post-dose), Day 12, and approximately Day 29 (immediately preceding subsequent dose))
- Estimates of infant exposure(Infant serum will be collected on approximately Day 30 following the next dose and after 24 hours of breast feeding)
- Maternal and Infant adverse events (AEs)(Total duration of participation for each participant will be approximately 1 month; data collection is planned for approximately 3 years)