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

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ClinicalTrials.gov Identifier: NCT02154425
Recruitment Status : Completed
First Posted : June 3, 2014
Results First Posted : February 6, 2017
Last Update Posted : April 3, 2018
Sponsor:
Collaborators:
PPD
Parexel
Information provided by (Responsible Party):
UCB Pharma ( UCB BIOSCIENCES, Inc. )

Tracking Information
First Submitted Date  ICMJE May 30, 2014
First Posted Date  ICMJE June 3, 2014
Results First Submitted Date  ICMJE December 8, 2016
Results First Posted Date  ICMJE February 6, 2017
Last Update Posted Date April 3, 2018
Study Start Date  ICMJE September 2014
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 8, 2016)
  • The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 0 [ Time Frame: Day 0 ]
    Mature breast milk samples were collected predose on Day 0 of the Sampling Period (CZP dosing day) for all subjects.
  • The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 2 [ Time Frame: Day 2 ]
    Mature breast milk samples were collected on Day 2 of the Sampling Period for all subjects.
  • The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 4 [ Time Frame: Day 4 ]
    Mature breast milk samples were collected on Day 4 of the Sampling Period for all subjects.
  • The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 6 [ Time Frame: Day 6 ]
    Mature breast milk samples were collected on Day 6 of the Sampling Period for all subjects.
  • The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 8 [ Time Frame: Day 8 ]
    Mature breast milk samples were collected on Day 8 of the Sampling Period for all subjects.
  • The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 10 [ Time Frame: Day 10 ]
    Mature breast milk samples were collected on Day 10 of the Sampling Period for all subjects.
  • The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 12 [ Time Frame: Day 12 ]
    Mature breast milk samples were collected on Day 12 of the Sampling Period for all subjects.
  • The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 14 [ Time Frame: 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.
  • The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 28 [ Time Frame: 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.
  • The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 2 [ Time Frame: Day 2 ]
    Mature breast milk samples was collected on Day 2 of the Sampling Period for all subjects.
  • The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 4 [ Time Frame: Day 4 ]
    Mature breast milk samples was collected on Day 4 of the Sampling Period for all subjects.
  • The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 6 [ Time Frame: Day 6 ]
    Mature breast milk samples was collected on Day 6 of the Sampling Period for all subjects.
  • The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 8 [ Time Frame: Day 8 ]
    Mature breast milk samples was collected on Day 8 of the Sampling Period for all subjects.
  • The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 10 [ Time Frame: Day 10 ]
    Mature breast milk samples was collected on Day 10 of the Sampling Period for all subjects.
  • The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 12 [ Time Frame: Day 12 ]
    Mature breast milk samples was collected on Day 12 of the Sampling Period for all subjects.
  • The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast on Day 14 [ Time Frame: 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.
  • The Calculated Infant Daily Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 28 [ Time Frame: 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.
  • The Average Daily Infant Dose of Certolizumab Pegol (CZP) Over the Dosing Interval (14 or 28 Days) [ Time Frame: From Day 0 to Day 14 or 28 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 30, 2014)
  • The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 0 [ Time Frame: Day 0 ]
    Mature breast milk samples will be collected predose on Day 0 of the Sampling Period (CZP dosing day) for all subjects.
  • The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 2 [ Time Frame: Day 2 ]
    Mature breast milk samples will be collected on Day 2 of the Sampling Period for all subjects.
  • The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 4 [ Time Frame: Day 4 ]
    Mature breast milk samples will be collected on Day 4 of the Sampling Period for all subjects.
  • The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 6 [ Time Frame: Day 6 ]
    Mature breast milk samples will be collected on Day 6 of the Sampling Period for all subjects.
  • The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 8 [ Time Frame: Day 8 ]
    Mature breast milk samples will be collected on Day 8 of the Sampling Period for all subjects.
  • The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 10 [ Time Frame: Day 10 ]
    Mature breast milk samples will be collected on Day 10 of the Sampling Period for all subjects.
  • The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 12 [ Time Frame: Day 12 ]
    Mature breast milk samples will be collected on Day 12 of the Sampling Period for all subjects.
  • The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 14 [ Time Frame: Day 14 ]
    Mature breast milk samples will be collected (predose, as applicable for subjects receiving CZP 200 mg Q2W) on Day 14 of the Sampling Period for all subjects.
  • The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 28 [ Time Frame: Day 28 ]
    In subjects receiving CZP 400 mg Q4W, a mature breast milk sample will be collected on or about Day 28, prior to the next scheduled administration of CZP.
  • The calculated infant daily dose of Certolizumab Pegol (CZP) in breast milk on Day 0 [ Time Frame: Day 0 ]
    Mature breast milk samples will be collected predose on Day 0 of the Sampling Period for all subjects.
  • The calculated infant daily dose of Certolizumab Pegol (CZP) in breast milk on Day 2 [ Time Frame: Day 2 ]
    Mature breast milk samples will be collected on Day 2 of the Sampling Period for all subjects.
  • The calculated infant daily dose of Certolizumab Pegol (CZP) in breast milk on Day 4 [ Time Frame: Day 4 ]
    Mature breast milk samples will be collected on Day 4 of the Sampling Period for all subjects.
  • The calculated infant daily dose of Certolizumab Pegol (CZP) in breast milk on Day 6 [ Time Frame: Day 6 ]
    Mature breast milk samples will be collected on Day 6 of the Sampling Period for all subjects.
  • The calculated infant daily dose of Certolizumab Pegol (CZP) in breast milk on Day 8 [ Time Frame: Day 8 ]
    Mature breast milk samples will be collected on Day 8 of the Sampling Period for all subjects.
  • The calculated infant daily dose of Certolizumab Pegol (CZP) in breast milk on Day 10 [ Time Frame: Day 10 ]
    Mature breast milk samples will be collected on Day 10 of the Sampling Period for all subjects.
  • The calculated infant daily dose of Certolizumab Pegol (CZP) in breast milk on Day 12 [ Time Frame: Day 12 ]
    Mature breast milk samples will be collected on Day 12 of the Sampling Period for all subjects.
  • The calculated infant daily dose of Certolizumab Pegol (CZP) in breast milk on Day 14 [ Time Frame: Day 14 ]
    Mature breast milk samples will be collected (predose, as applicable for subjects receiving CZP 200 mg Q2W) on Day 14 of the Sampling Period for all subjects.
  • The calculated infant daily dose of Certolizumab Pegol (CZP) in breast milk on Day 28 [ Time Frame: Day 28 ]
    In subjects receiving CZP 400 mg Q4W, a mature breast milk sample will be collected on or about Day 28, prior to the next scheduled administration of CZP.
Change History Complete list of historical versions of study NCT02154425 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Multicenter, Postmarketing Study Evaluating the Concentration of Cimzia® in Mature Breast Milk of Lactating Mothers
Official Title  ICMJE A Multicenter, Postmarketing Study to Evaluate the Concentration of Certolizumab Pegol in the Breast Milk of Mothers Receiving Treatment With Cimzia® (Certolizumab Pegol)
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE
  • Axial Spondyloarthritis (AxSpA)
  • Non-radiographic Evidence-AxSpA
  • Ankylosing Spondylitis
  • Crohn's Disease
  • Psoriatic Arthritis
  • Rheumatoid Arthritis
Intervention  ICMJE
  • 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 Name: Cimzia®
Study Arms  ICMJE 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.

Interventions:
  • Procedure: Breast milk sampling
  • Biological: Certolizumab Pegol
Publications * Clowse ME, Förger 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 3, 2015)
17
Original Estimated Enrollment  ICMJE
 (submitted: May 30, 2014)
16
Actual Study Completion Date  ICMJE January 2016
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands,   Switzerland,   United States
Removed Location Countries France
 
Administrative Information
NCT Number  ICMJE NCT02154425
Other Study ID Numbers  ICMJE UP0016
2013-004126-28 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party UCB Pharma ( UCB BIOSCIENCES, Inc. )
Study Sponsor  ICMJE UCB BIOSCIENCES, Inc.
Collaborators  ICMJE
  • PPD
  • Parexel
Investigators  ICMJE
Study Director: UCB Cares +1 877 822 9493 (UCB)
PRS Account UCB Pharma
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP