Systemic Lupus Erythematosus
Conditions
Keywords
Chronic autoimmune disease, Immunosuppressants, Corticosteroids, Human monoclonal antibody (IgG1ƙ mAb), Post Marketing Requirements (PMR) study, Systemic Lupus Erythematosus (SLE)
Brief summary
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.
Detailed description
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.
Interventions
DRUGAnifrolumab
Anifrolumab is a human monoclonal antibody that binds to subunit 1 of the type 1 interferon receptor, which was developed based on the evidence supporting the role of type 1 interferon pathway in SLE (Furie et al., 2017). Clinical trial evidence from TULIP 1, TULIP 2 have showed that monthly intravenous administration of anifrolumab led to a higher percentage of patients with a response, assessed with the British Isles Lupus Assessment Group-based Composite Lupus Assessment, compared with patients receiving placebo (Furie et al., 2019; Morand et al., 2020). The phase II MUSE study showed that administration of anifrolumab resulted in substantially reduced disease activity, measured by the SLE Responder Index, compared to patients receiving placebo (Furie et al., 2017). These data resulted with applications to the FDA and the EMA, leading to approvals in July 2021 and February 2022, for the treatment of adult patients with moderate to severe SLE who are receiving standard therapy.
Sponsors
AstraZeneca
PPD Development, LP
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
Maternal: 1. 18 years or older 2. Signed informed consent to participate 3. Diagnosis of moderate/severe SLE 4. Ongoing treatment with anifrolumab 5. 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) 6. 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) 7. 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 8. Plans to continue feeding infant breast milk at least throughout the duration of the study and is not weaning 9. 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 10. Agrees to use only lanolin nipple cream during the sampling period Infant: 1. Gestational age at delivery ≥32 weeks 2. Birthweight \> 10th percentile 3. Weight \> 10th percentile at the time of enrollment
Exclusion criteria
Maternal: 1. 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 2. Diagnosis of lupus nephritis in the last 12 months 3. History of breast implants, breast augmentation, or breast reduction surgery that significantly impacts breastfeeding or collection of milk from 1 or both breasts 4. History of malignancy in the last 10 years 5. History of mastectomy 6. Evidence of mastitis or any other significant active infection at Day 1 (pre-dose) Infant: 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the milk concentration-time curve during a dosing interval | 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 | 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 | 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 | 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 | 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total amount of drug excreted in milk over 24 hours | Day 1 | Variable used to assess total amount of drug excreted in milk of lactating individuals. Total amount of drug excreted in milk (mg) over 24 hours calculated as: Σ(total drug concentration in each milk collection x milk volume in each milk collection) |
| Fraction of dose excreted in milk | Day 1 | Variable used to assess fraction of anifrolumab dose excreted in milk of lactating individuals. Fraction of dose excreted in milk, calculated as (Total amount of drug excreted in milk over 24 hours)/Administered dose |
| 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) | Variable used to assess maternal serum pharmacokinetic (PK) concentrations |
| Estimates of infant exposure | Infant serum will be collected on approximately Day 30 following the next dose and after 24 hours of breast feeding | Variable used to assess infant anifrolumab exposure (daily infant dosage; relative infant dosage; infant serum anifrolumab concentration) |
| 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 | Collection of maternal and/or infant AEs during study period. AEs will be summarized by system organ class, preferred term, severity, and causal relationship to anifrolumab |
Countries
United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
PRINCIPAL_INVESTIGATORDarin Brimhall, MD
PPD, Las Vegas, US
Outcome results
None listed