Ankylosing Spondylitis, Axial Spondyloarthritis (AxSpA), Crohn's Disease, Non-radiographic Evidence-AxSpA, Psoriatic Arthritis, Rheumatoid Arthritis
Conditions
Keywords
Cimzia®, CZP, Placental transfer, Autoimmune diseases and pregnancy
Brief summary
The primary purpose is to assess whether there is transfer of Certolizumab Pegol (CZP) from pregnant women receiving treatment with Cimzia® across the placenta to infants by evaluating the concentration of CZP in the plasma of infants at birth.
Interventions
PROCEDUREBlood sampling from mother
A blood sample from the mother will be taken within 24 hours before/after the delivery.
PROCEDUREBlood sampling from infant
Blood samples from the infant will be taken within 24 hours after birth, at Week 4 and at Week 8.
PROCEDUREBlood sampling from umbilical cord
A blood sample from the umbilical cord will be taken directly (within 1 hour ) after delivery.
BIOLOGICALCertolizumab Pegol
Mothers who decided to continue on, or to start treatment with, 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. * Active Substance: Certolizumab Pegol * Pharmaceutical Form: Solution for injection * Concentration: 200 mg/ml * Route of Administration: Subcutaneous Use
Sponsors
PPD Development, LP
Parexel
UCB BIOSCIENCES, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* An IRB/IEC approved written Informed Consent form for the maternal subject and her infant(s) is signed and dated by the subject. Where applicable, the written Informed Consent form with respect to the infant(s) 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 ≥18 years at the time of informed consent * Subject is ≥30 weeks pregnant with a singleton or twins at the time of informed consent * Subject is being treated with Certolizumab Pegol (CZP) per the current approved prescribing Information * Subject started or decided to continue treatment with CZP independently from and prior to participating in this study and in accordance with the treating physician * Subject expects to receive CZP until at least 35 days prior to expected delivery (date of injection counted as Day 1) Additional criteria to be confirmed prior to first sample from infant at Visit 2 (delivery/birth): * Subject delivers a live born infant(s) at or near term (≥34 weeks gestation ) * Subject received CZP within 35 days before delivery (date of injection counted as Day 1) * Subject has not received contraindicated medication
Exclusion criteria
* Subject has participated in a study of an investigational medicinal product (IMP) or 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 medical device - unless the study is UCB UP0016 \[NCT02154425\] or a registry study * Subject has any obstetrical or psychiatric condition, or she or her infant(s) has any medical condition that, in the opinion of the Investigator, could jeopardize or would compromise the subject's ability to participate in this study or the outcome of the pregnancy * Subject has history of chronic alcohol abuse or drug abuse during pregnancy * Subject has any pregnancy-related clinically significant abnormality noted on obstetric ultrasound, or other imaging assessment, or the subject has significant laboratory abnormalities during her pregnancy, as judged by the Investigator * Subject is taking or has taken any medication with strong positive evidence of a human fetal risk of teratogenicity (e.g., methotrexate or leflunomide) during pregnancy * Subject has evidence of a condition suggesting chronic or acute uteroplacental insufficiency such as intrauterine growth restriction, severe maternal hypertensive disorders of pregnancy, or abruption * Subject has a documented history of primary or secondary antiphospholipid syndrome or hypercoagulable state * Subject has received treatment with any biological therapeutic agent, including anti-TNFs other than certolizumab pegol (CZP), during pregnancy * Subject has previously participated in this study * 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 infection (LTB). If tested within the 6 months prior to Screening and the test was negative for TB, and there is no change in the subject'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 Plasma Concentration of Certolizumab Pegol (CZP) in the Infant(s) at Birth | Day 0 | Blood samples will be taken within 24 hours after birth from the infant(s). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Plasma Concentration Level of Anti-CZP Antibodies in the Umbilical Cord(s) at Birth | Day 0 | Blood samples will be taken directly after delivery (within \<= 1 hour) from the umbilical cord |
| The Plasma Concentration of Certolizumab Pegol (CZP) in the Mother at Delivery | Day 0 | Blood samples will be taken within 24 hours before/after delivery from the mothers. |
| The Ratio of Plasma Concentration of Certolizumab Pegol (CZP) Between the Infant(s) and Mother at Delivery/Birth | Day 0 | Blood samples were taken within 24 hours before/after delivery from the mothers and within 24 hours after birth from the infant(s). Values below limit of quantification (BLQ) are replaced by values of lower limit of quantification/2=0.016 in calculations of ratios, however if both concentrations for a subject are BLQ then the ratio for that subject will not be calculated. |
| The Plasma Concentration of Certolizumab Pegol (CZP) in the Umbilical Cord at Birth | Day 0 | Blood samples will be taken directly after delivery (within \<= 1 hour) from the umbilical cord |
| The Plasma Concentration Level of Anti-CZP Antibodies in the Mother at Delivery | Day 0 | Blood samples will be taken within 24 hours before/after delivery from the mothers |
Countries
France, Netherlands, Switzerland, United States
Participant flow
Recruitment details
The study started to enroll patients in January 2014 and concluded in November 2016.
Pre-assignment details
The Participant Flow refers to the Safety Set for Mothers \[SS-M\] and the Safety Set for Infants \[SS-I\]. For mothers, Baseline is defined as their screening visit. Since babies are regarded as study participants once they are born, baseline for the infants is considered to be the day of their birth.
Participants by arm
| Arm | Count |
|---|---|
| SS-M This arm consisted of all participating mothers who entered the screening period and received at least 1 dose of Certolizumab Pegol (CZP) less than or equal to 35 days prior to delivery. | 21 |
| SS-I This arm consisted of all infants born to mothers in the SS-M group. | 16 |
| Total Title | 37 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Screening Period | Adverse Event | 1 | 0 |
| Screening Period | Ineligibility | 4 | 0 |
Baseline characteristics
| Characteristic | SS-M | SS-I | Total Title |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 16 Participants | 16 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 0 Participants | 21 Participants |
| Age, Continuous Infants | — | 0 years STANDARD_DEVIATION 0 | 0 years STANDARD_DEVIATION 0 |
| Age, Continuous Mothers | 31.4 years STANDARD_DEVIATION 5 | — | 31.4 years STANDARD_DEVIATION 5 |
| Race/Ethnicity, Customized White | 21 Participants | 16 Participants | 37 Participants |
| Sex: Female, Male Female | 21 Participants | 10 Participants | 31 Participants |
| Sex: Female, Male Male | 0 Participants | 6 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 16 |
| other Total, other adverse events | 3 / 21 | 4 / 16 |
| serious Total, serious adverse events | 7 / 21 | 2 / 16 |
Outcome results
Primary
The Plasma Concentration of Certolizumab Pegol (CZP) in the Infant(s) at Birth
Blood samples will be taken within 24 hours after birth from the infant(s).
Time frame: Day 0
Population: Of the 16 infants in the SS-I, two were excluded from the Pharmacokinetic Per-Protocol Set for Infants (PK-PPS-I): one due to missing data at birth and one due to implausible PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PK-PPS-I | The Plasma Concentration of Certolizumab Pegol (CZP) in the Infant(s) at Birth | NA µg/mL |
Secondary
The Plasma Concentration Level of Anti-CZP Antibodies in the Mother at Delivery
Blood samples will be taken within 24 hours before/after delivery from the mothers
Time frame: Day 0
Population: The Pharmacokinetic Set for Mothers (PKS-M) consisted of all mothers who provided the CZP concentration sample at delivery.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PK-PPS-I | The Plasma Concentration Level of Anti-CZP Antibodies in the Mother at Delivery | NA units/mL |
Secondary
The Plasma Concentration Level of Anti-CZP Antibodies in the Umbilical Cord(s) at Birth
Blood samples will be taken directly after delivery (within \<= 1 hour) from the umbilical cord
Time frame: Day 0
Population: The Pharmacokinetic Set for Umbilical Cords (PKS-U) consisted of all umbilical cords of infants from which a CZP concentration sample was obtained at birth.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PK-PPS-I | The Plasma Concentration Level of Anti-CZP Antibodies in the Umbilical Cord(s) at Birth | NA units/mL |
Secondary
The Plasma Concentration of Certolizumab Pegol (CZP) in the Mother at Delivery
Blood samples will be taken within 24 hours before/after delivery from the mothers.
Time frame: Day 0
Population: The Pharmacokinetic Set for Mothers (PKS-M) consisted of all mothers who provided the CZP concentration sample at delivery.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PK-PPS-I | The Plasma Concentration of Certolizumab Pegol (CZP) in the Mother at Delivery | 24.40 µg/mL |
Secondary
The Plasma Concentration of Certolizumab Pegol (CZP) in the Umbilical Cord at Birth
Blood samples will be taken directly after delivery (within \<= 1 hour) from the umbilical cord
Time frame: Day 0
Population: The Pharmacokinetic Set for Umbilical Cords (PKS-U) consisted of all umbilical cords of infants from which a CZP concentration sample was obtained at birth.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PK-PPS-I | The Plasma Concentration of Certolizumab Pegol (CZP) in the Umbilical Cord at Birth | NA µg/mL |
Secondary
The Ratio of Plasma Concentration of Certolizumab Pegol (CZP) Between the Infant(s) and Mother at Delivery/Birth
Blood samples were taken within 24 hours before/after delivery from the mothers and within 24 hours after birth from the infant(s). Values below limit of quantification (BLQ) are replaced by values of lower limit of quantification/2=0.016 in calculations of ratios, however if both concentrations for a subject are BLQ then the ratio for that subject will not be calculated.
Time frame: Day 0
Population: The number of subjects' data analyzed is 28 since these are ratios for the infants and their mothers and for each ratio, we need both data. Please note that PK-PPS-I analysis set is defined as the number of infants which is 14 which is why it seems to have some discrepancies. This is due to the unique study design with mother and infant pair.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PK-PPS-I | The Ratio of Plasma Concentration of Certolizumab Pegol (CZP) Between the Infant(s) and Mother at Delivery/Birth | 0.0007634 ratio |