Axial Spondyloarthritis (AxSpA), Non-radiographic Evidence-AxSpA, Ankylosing Spondylitis, Crohn's Disease, Psoriatic Arthritis, Rheumatoid Arthritis
Conditions
Keywords
Cimzia®, CZP, Breastfeeding, Nursing, Autoimmune diseases and pregnancy
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.
Interventions
PROCEDUREBreast 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).
BIOLOGICALCertolizumab 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.
Sponsors
PPD Development, LP
Parexel
UCB BIOSCIENCES, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 0 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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) | 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. |
Countries
Netherlands, Switzerland, United States
Participant flow
Recruitment details
The study started to enroll patients in September 2014 and concluded in December 2015.
Pre-assignment details
The Participant Flow refers to the Safety Set which consisted of 18 mothers, who were screened and had received at least one dose of Certolizumab Pegol (CZP), but only 17 mothers entered the study (Enrollment number), as one subject was a screen failure.
Participants by arm
| Arm | Count |
|---|---|
| Mothers (SS) This arm consisted of all participating mothers who had received at least 1 dose of Certolizumab Pegol (CZP). | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Screening Period | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Mothers (SS) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Age, Continuous arithmetic mean (standard deviation) | 33.7 years STANDARD_DEVIATION 4.2 |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 18 | 8 / 17 |
| serious Total, serious adverse events | 1 / 18 | 0 / 17 |
Outcome results
Primary
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.
Time frame: From Day 0 to Day 14 or 28
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all subjects with a valid CZP concentration measurement in breast milk with no important protocol deviations affecting the primary variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mothers CZP (PK-PPS) Q2W | The Average Daily Infant Dose of Certolizumab Pegol (CZP) Over the Dosing Interval (14 or 28 Days) | 0.003503 mg/kg/day |
Primary
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.
Time frame: Day 10
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all subjects with a valid CZP concentration measurement in breast milk with no important protocol deviations affecting the primary variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mothers CZP (PK-PPS) Q2W | The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 10 | 0 mg/kg/day |
Primary
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.
Time frame: Day 12
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all subjects with a valid CZP concentration measurement in breast milk with no important protocol deviations affecting the primary variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mothers CZP (PK-PPS) Q2W | The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 12 | 0 mg/kg/day |
Primary
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.
Time frame: Day 2
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all subjects with a valid CZP concentration measurement in breast milk with no important protocol deviations affecting the primary variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mothers CZP (PK-PPS) Q2W | The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 2 | 0 mg/kg/day |
Primary
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.
Time frame: Day 4
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all subjects with a valid CZP concentration measurement in breast milk with no important protocol deviations affecting the primary variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mothers CZP (PK-PPS) Q2W | The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 4 | 0.005306 mg/kg/day |
Primary
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.
Time frame: Day 6
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all subjects with a valid CZP concentration measurement in breast milk with no important protocol deviations affecting the primary variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mothers CZP (PK-PPS) Q2W | The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 6 | 0.005604 mg/kg/day |
Primary
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.
Time frame: Day 8
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all subjects with a valid CZP concentration measurement in breast milk with no important protocol deviations affecting the primary variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mothers CZP (PK-PPS) Q2W | The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 8 | 0.005606 mg/kg/day |
Primary
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.
Time frame: Day 14
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all subjects with a valid CZP concentration measurement in breast milk with no important protocol deviations affecting the primary variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mothers CZP (PK-PPS) Q2W | The Calculated Daily Infant Dose of Certolizumab Pegol (CZP) in Breast on Day 14 | 0 mg/kg/day |
Primary
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.
Time frame: Day 28
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all subjects with a valid CZP concentration measurement in breast milk with no important protocol deviations affecting the primary variable. Measurement on day 28 applies to subjects on a CZP 400mg Q4W dosing regimen only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mothers CZP (PK-PPS) Q2W | The Calculated Infant Daily Dose of Certolizumab Pegol (CZP) in Breast Milk on Day 28 | 0 mg/kg/day |
Primary
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.
Time frame: Day 0
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all subjects with a valid CZP concentration measurement in breast milk with no important protocol deviations affecting the primary variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mothers CZP (PK-PPS) Q2W | The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 0 | NA µg/mL |
| Mothers CZP (PK-PPS) Q4W | The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 0 | NA µg/mL |
Primary
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.
Time frame: Day 10
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all subjects with a valid CZP concentration measurement in breast milk with no important protocol deviations affecting the primary variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mothers CZP (PK-PPS) Q2W | The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 10 | NA µg/mL |
| Mothers CZP (PK-PPS) Q4W | The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 10 | NA µg/mL |
Primary
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.
Time frame: Day 12
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all subjects with a valid CZP concentration measurement in breast milk with no important protocol deviations affecting the primary variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mothers CZP (PK-PPS) Q2W | The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 12 | NA µg/mL |
| Mothers CZP (PK-PPS) Q4W | The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 12 | NA µg/mL |
Primary
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.
Time frame: Day 14
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all subjects with a valid CZP concentration measurement in breast milk with no important protocol deviations affecting the primary variable.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Mothers CZP (PK-PPS) Q2W | The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 14 | NA µg/mL |
| Mothers CZP (PK-PPS) Q4W | The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 14 | NA µg/mL |
Primary
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.
Time frame: Day 2
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all subjects with a valid CZP concentration measurement in breast milk with no important protocol deviations affecting the primary variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mothers CZP (PK-PPS) Q2W | The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 2 | NA µg/mL |
| Mothers CZP (PK-PPS) Q4W | The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 2 | NA µg/mL |
Primary
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.
Time frame: Day 28
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all subjects with a valid CZP concentration measurement in breast milk with no important protocol deviations affecting the primary variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mothers CZP (PK-PPS) Q2W | The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 28 | NA µg/mL |
Primary
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.
Time frame: Day 4
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all subjects with a valid CZP concentration measurement in breast milk with no important protocol deviations affecting the primary variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mothers CZP (PK-PPS) Q2W | The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 4 | 0.03578 µg/mL |
| Mothers CZP (PK-PPS) Q4W | The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 4 | NA µg/mL |
Primary
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.
Time frame: Day 6
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all subjects with a valid CZP concentration measurement in breast milk with no important protocol deviations affecting the primary variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mothers CZP (PK-PPS) Q2W | The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 6 | 0.03739 µg/mL |
| Mothers CZP (PK-PPS) Q4W | The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 6 | NA µg/mL |
Primary
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.
Time frame: Day 8
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all subjects with a valid CZP concentration measurement in breast milk with no important protocol deviations affecting the primary variable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mothers CZP (PK-PPS) Q2W | The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 8 | 0.03899 µg/mL |
| Mothers CZP (PK-PPS) Q4W | The Concentration of Certolizumab Pegol (CZP) in Breast Milk on Day 8 | NA µg/mL |