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

NCT02154425 | Completed Phase 1 Results

• 2 other identifiers: UP00162013-004126-28
• Study Type: interventional
• Target: 17
• Locations: 3 countries
• Sites: 6

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.

Conditions

Axial Spondyloarthritis (AxSpA); Non-radiographic Evidence-AxSpA; Ankylosing Spondylitis; Crohn's Disease; Psoriatic Arthritis; Rheumatoid Arthritis

Keywords

Cimzia®; CZP; Breastfeeding; Nursing; Autoimmune diseases and pregnancy

Outcome Measures

Primary Outcomes (18)

• 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

Study Arms (1)

Pharmacokinetic samples

EXPERIMENTAL

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; Biological: Certolizumab Pegol

Interventions

Breast milk sampling PROCEDURE

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).

Pharmacokinetic samples

Certolizumab Pegol BIOLOGICAL

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.

Also known as: Cimzia®

Pharmacokinetic samples

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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 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

Sponsors & Collaborators

• UCB BIOSCIENCES, Inc.: lead
• PPD Development, LP: collaborator
• Parexel: collaborator

Study Sites (6)

7

Los Angeles, California, United States

Location

1

Chapel Hill, North Carolina, United States

Location

3

Durham, North Carolina, United States

Location

500

Maastricht, Netherlands

Location

501

Rotterdam, Netherlands

Location

20

Bern, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 28814432 RESULT

MeSH Terms

Conditions

Axial Spondyloarthritis; Spondylitis, Ankylosing; Crohn Disease; Arthritis, Psoriatic; Arthritis, Rheumatoid; Breast Feeding; Autoimmune Diseases

Interventions

Certolizumab Pegol

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases; Rheumatic Diseases; Connective Tissue Diseases; Immune System Diseases; Feeding Behavior; Behavior

Intervention Hierarchy (Ancestors)

Polyethylene Glycols; Polymers; Macromolecular Substances; Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: UCB
• Organization: Cares

+1877 822

Study Officials

• UCB Cares

  +1 877 822 9493 (UCB)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2014
• First Posted: June 3, 2014
• Study Start: September 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: January 1, 2016
• Last Updated: April 3, 2018
• Results First Posted: February 6, 2017

Record last verified: 2018-03

Locations

US (3); NL (2); CH (1)