Prospective Registry Investigating Maternal, Infant, and Lactation Outcomes in Anifrolumab Users

Official title

PRIMULA Lac (Prospective Registry Investigating Maternal, Infant, and Lactation Outcomes in Anifrolumab Users): The AstraZeneca Lactation Study for Anifrolumab

Overview

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

• Drug Anifrolumab
  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 patien

Primary outcome measures

• Area under the milk concentration-time curve during a dosing interval [Time frame: Approximately 30 days]
• Area under the milk concentration-time curve from time 0 to last quantifiable concentration [Time frame: Approximately 30 days]
• Average milk concentration at steady state [Time frame: Approximately 30 days]
• Observed milk concentration at end of dosing interval [Time frame: Approximately 30 days]
• Maximum observed milk concentration [Time frame: Approximately 30 days]
• Time of maximum concentration [Time frame: Approximately 30 days]

Secondary outcome measures (5)

• Total amount of drug excreted in milk over 24 hours [Time frame: Day 1]
• Fraction of dose excreted in milk [Time frame: Day 1]
• Maternal serum pharmacokinetic (PK) concentrations [Time frame: 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 [Time frame: 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) [Time frame: Total duration of participation for each participant will be approximately 1 month; data collection is planned for approximately 3 years]

Eligibility criteria

Inclusion criteria

Maternal:

• 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

Infant:

• Gestational age at delivery ≥32 weeks
• Birthweight > 10th percentile
• Weight > 10th percentile at the time of enrollment

Exclusion criteria

Maternal:

• 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)

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Research Site — Las Vegas

Identifiers

NCT: NCT06594068 · D3461R00052

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗