Prospective Registry Investigating Maternal, Infant, and Lactation Outcomes in Anifrolumab Users (PRIMULA Lac)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Anifrolumab

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.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• United States
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

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 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the milk concentration-time curve during a dosing interval	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	Approximately 30 days
Area under the milk concentration-time curve from time 0 to last quantifiable concentration	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	Approximately 30 days
Average milk concentration at steady state	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	Approximately 30 days
Observed milk concentration at end of dosing interval	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	Approximately 30 days
Maximum observed milk concentration	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	Approximately 30 days
Time of maximum concentration	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	Approximately 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total amount of drug excreted in milk over 24 hours	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)	Day 1
Fraction of dose excreted in milk	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	Day 1
Maternal serum pharmacokinetic (PK) concentrations	Variable used to assess 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	Variable used to assess infant anifrolumab exposure (daily infant dosage; relative infant dosage; infant serum anifrolumab concentration)	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)	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	Total duration of participation for each participant will be approximately 1 month; data collection is planned for approximately 3 years

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: PPD Development, LP
• Investigators: Principal Investigator: Darin Brimhall, MD, PPD, Las Vegas, US

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2026
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: September 10, 2024
• First Submitted That Met QC Criteria: September 10, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): August 18, 2026
• Last Update Submitted That Met QC Criteria: August 17, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Systemic Lupus Erythematosus (SLE); Corticosteroids; Immunosuppressants; Chronic autoimmune disease; Human monoclonal antibody (IgG1ƙ mAb); Post Marketing Requirements (PMR) study
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; anifrolumab
• Other Study ID Numbers: D3461R00052

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from

AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No