A Multicenter, Postmarketing Study Evaluating the Concentration of Cimzia® in Mature Breast Milk of Lactating Mothers (CRADLE)

A Multicenter, Postmarketing Study to Evaluate the Concentration of Certolizumab Pegol in the Breast Milk of Mothers Receiving Treatment With Cimzia® (Certolizumab Pegol)

The primary objectives of this study are to assess whether there is transfer of Certolizumab Pegol (CZP) into breast milk of lactating mothers who are receiving an established dosing regimen of CZP by evaluating the concentration of CZP in mature breast milk, and to calculate the daily infant dose of maternal CZP.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis; Crohn's Disease; Psoriatic Arthritis; Ankylosing Spondylitis; Axial Spondyloarthritis (AxSpA); Non-radiographic Evidence-AxSpA
• Intervention / Treatment: Procedure: Breast milk sampling; Biological: Certolizumab Pegol

Detailed Description

The study will only include women who are receiving treatment with Certolizumab Pegol (CZP) for an approved indication in accordance with their treating physician, although this study is non-interventional regarding treatment with CZP, it is considered interventional due to the collection of breast milk from the lactating mothers.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands
    • 500
  • Rotterdam, Netherlands
    • 501
• Switzerland
  • Bern, Switzerland
    • 20
• United States
  • California
    • Los Angeles, California, United States
      • 7
  • North Carolina
    • Chapel Hill, North Carolina, United States
      • 1
    • Durham, North Carolina, United States
      • 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• An IRB/IEC approved written Informed Consent form for participation of the maternal subject and her infant (for collection of infant demographic and AE data) is signed and dated by the subject. Where applicable, the written Informed Consent form with respect to the infant is also signed and dated by the holder of parental rights as designated by the maternal subject
• Subject is considered reliable and capable of adhering to the protocol and visit schedule according to the judgment of the Investigator
• Subject is female and at least 18 years of age at the time of providing consent
• Subject has delivered term infant(s) (at least 37 weeks gestation)
• Subject is being treated with Certolizumab Pegol (CZP) per the current approved prescribing information
• The decision to treat with CZP or to breastfeed is made independently from and prior to the subject consenting to participate in this study
• Subject agrees to use only the emollient or nipple cream provided by the Sponsor for use during the Sampling Period as described per protocol
• Subject is at least 6 weeks postpartum
• Subject is on an established dosing regimen of CZP (at least the third dose of CZP since starting/restarting CZP)

Exclusion Criteria:

• Subject is pregnant or plans to become pregnant during the study
• Subject is taking a prohibited medication or has taken a prohibited medication Note: any subjects requiring antibiotics must be discussed with the Medical Monitor prior to enrollment
• Subject has history of chronic alcohol abuse or drug abuse in the last year
• In subjects who intend to breastfeed, the infant has any abnormality noted on physical examination that, in the opinion of the Investigator, may jeopardize or compromise the subject's ability to participate in this study
• Subject has any medical, obstetrical or psychiatric condition that, in the opinion of the Investigator, can jeopardize or would compromise the subject's ability to participate in this study or the outcome of the pregnancy (as applicable). Note: subjects with mastitis infection should not have samples collected until the infection is completely resolved
• Subject has history of breast implants, breast augmentation, or breast reduction surgery
• Subject has previously participated in this study
• Subject has participated in a study of an investigational medicinal product (IMP) (or a medical device) within the previous 30 days or 5 half-lives (whichever is longer) prior to Screening or is currently participating in another study of an IMP (or a medical device) unless the study is UCB UP0017 [NCT02019602] or a registry study
• Subject has received treatment with any biological therapeutic agent, or other anti-TNF agents with the exception of CZP, within 5 half-lives prior to obtaining the first sample
• Subject has a positive or indeterminate QuantiFERON®-TB GOLD In Tube test at Screening. In case of indeterminate result, a retest is allowed if time permits; 2 results of indeterminate require exclusion of the subject
• Subject with known tuberculosis (TB) infection, at high risk of acquiring TB infection, or latent TB (LTB) infection. If tested within the 6 months prior to screening and test was negative for TB, and there is no change in the patient's clinical status, nor social, family, or travel history, there is no need for an additional TB testing at screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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: Pharmacokinetic samples; Pharmacokinetic (PK) samples will be taken from breast milk of lactating mothers on an established dosing regimen of CZP on Day 0 of the Sampling Period, just prior to next scheduled dose of CZP, and on Days 2, 4, 6, 8, 10, 12, and 14 (pre-dose if Q2W dosing), relative to CZP administration on Day 0. In addition, in mothers on a CZP Q4W dosing regimen, the concentration of CZP in breast milk will also be evaluated on or about Day 28 (i.e., prior to and on the same day of the next scheduled administration of CZP). Included are mothers who decided to continue on, or to start treatment with, Certolizumab Pegol (CZP) for an approved indication with their treating physician prior to participation into this study. The mother is responsible for procuring her own supply of commercial CZP. The CZP dose and administration schedule will be as per the locally approved label.

Procedure: Breast milk sampling; Pharmacokinetic (PK) samples will be taken from breast milk of lactating mothers on an established dosing regimen of CZP on Day 0 of the Sampling Period, just prior to next scheduled dose of CZP, and on Days 2, 4, 6, 8, 10, 12, and 14 (pre-dose for mothers on CZP Q2W), relative to CZP administration on Day 0. In addition, in mothers on a CZP Q4W dosing regimen, the concentration of CZP in breast milk will also be evaluated on or about Day 28 (i.e., prior to and on the same day of the next scheduled administration of CZP).; Biological: Certolizumab Pegol; Mothers who decided to continue on, or to start treatment with, Certolizumab Pegol (CZP) for an approved indication with their treating physician prior to participation into this study. The mother is responsible for procuring her own supply of commercial CZP. The CZP dose and administration schedule will be as per the locally approved label.; Other Names: Cimzia®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 0	Mature breast milk samples were collected predose on Day 0 of the Sampling Period (CZP dosing day) for all subjects.	Day 0
The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 2	Mature breast milk samples were collected on Day 2 of the Sampling Period for all subjects.	Day 2
The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 4	Mature breast milk samples were collected on Day 4 of the Sampling Period for all subjects.	Day 4
The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 6	Mature breast milk samples were collected on Day 6 of the Sampling Period for all subjects.	Day 6
The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 8	Mature breast milk samples were collected on Day 8 of the Sampling Period for all subjects.	Day 8
The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 10	Mature breast milk samples were collected on Day 10 of the Sampling Period for all subjects.	Day 10
The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 12	Mature breast milk samples were collected on Day 12 of the Sampling Period for all subjects.	Day 12
The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 14	Mature breast milk samples were collected (predose, as applicable for subjects receiving CZP 200 mg Q2W) on Day 14 of the Sampling Period for all subjects.	Day 14
The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 28	In subjects receiving CZP 400 mg Q4W, a mature breast milk sample were collected on or about Day 28, prior to the next scheduled administration of CZP.	Day 28
The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 2	Mature breast milk samples was collected on Day 2 of the Sampling Period for all subjects.	Day 2
The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 4	Mature breast milk samples was collected on Day 4 of the Sampling Period for all subjects.	Day 4
The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 6	Mature breast milk samples was collected on Day 6 of the Sampling Period for all subjects.	Day 6
The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 8	Mature breast milk samples was collected on Day 8 of the Sampling Period for all subjects.	Day 8
The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 10	Mature breast milk samples was collected on Day 10 of the Sampling Period for all subjects.	Day 10
The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 12	Mature breast milk samples was collected on Day 12 of the Sampling Period for all subjects.	Day 12
The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast on Day 14	Mature breast milk samples was collected (pre-dose, as applicable for subjects receiving CZP 200 mg Q2W) on Day 14 of the Sampling Period for all subjects.	Day 14
The Calculated Infant Daily Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 28	In subjects receiving CZP 400 mg Q4W, a mature breast milk sample was collected on or about Day 28, prior to the next scheduled administration of CZP.	Day 28
The Average Daily Infant Dose of Certolizumab Pegol (CZP) Over the Dosing Interval (14 or 28 Days)	Mature breast milk samples will be collected (pre-dose, as applicable for subjects receiving CZP 200 mg Q2W) on Day 14 or on Day 28 of the Sampling Period for all subjects.	From Day 0 to Day 14 or 28

Collaborators and Investigators

• Sponsor: UCB BIOSCIENCES, Inc.
• Collaborators: PPD; Parexel

Publications and helpful links

General Publications

• Clowse ME, Forger F, Hwang C, Thorp J, Dolhain RJ, van Tubergen A, Shaughnessy L, Simpson J, Teil M, Toublanc N, Wang M, Hale TW. Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study. Ann Rheum Dis. 2017 Nov;76(11):1890-1896. doi: 10.1136/annrheumdis-2017-211384. Epub 2017 Aug 16.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: May 30, 2014
• First Submitted That Met QC Criteria: May 30, 2014
• First Posted (Estimate): June 3, 2014

Study Record Updates

• Last Update Posted (Actual): April 3, 2018
• Last Update Submitted That Met QC Criteria: March 8, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Nursing; Breastfeeding; CZP; Cimzia®; Autoimmune diseases and pregnancy
• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Infections; Gastrointestinal Diseases; Joint Diseases; Musculoskeletal Diseases; Gastroenteritis; Intestinal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Inflammatory Bowel Diseases; Spondylarthropathies; Psoriasis; Bone Diseases, Infectious; Ankylosis; Arthritis; Crohn Disease; Arthritis, Psoriatic; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing; Physiological Effects of Drugs; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Certolizumab Pegol
• Other Study ID Numbers: UP0016; 2013-004126-28 (EudraCT Number)