Axial Spondyloarthritis, Crohn's Disease, Plaque Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis
Conditions
Keywords
Cimzia, Certolizumab Pegol, Pregnant Women, Crohn's Disease (CD), Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA), Plaque Psoriasis (PSO), Axial Spondyloarthritis (AxSpA), Pharmacokinetics, CZP
Brief summary
The purpose of the study is to assess systemic certolizumab pegol (CZP) exposure, the formation of anti-CZP antibodies and safety of CZP across the course of pregnancy in study participants with chronic inflammatory diseases.
Interventions
DRUGPharmacokinetics of certolizumab pegol
The collection of blood samples for pharmacokinetics (PK) is considered interventional. Blood samples will be drawn at enrollment, predose every 4 weeks (Q4W), postdose every 8 weeks (Q8W) and postpartum predose and postdose. Study participants will be responsible for obtaining and administering commercially available approved dosing regimens of certolizumab pegol (CZP) as prescribed by each study participant's own physician.
Sponsors
UCB Biopharma SRL
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant is pregnant and ≤10 weeks gestation at the time of enrollment * Participant must have been on stable, maintenance dose certolizumab pegol (CZP) treatment for at least 12 weeks independent of and prior to being enrolled in this study, for an approved indication in accordance with her treating physician * Participant expects to continue CZP therapy throughout pregnancy and for at least 12 weeks postpartum * Participant has a negative interferon gamma release assay (IGRA) or tuberculin skin test (TST) within the prior 6 months, and there has been no change in the study participant's clinical status, or social, family, or travel history. Participants with documented Bacillus Calmette-Guérin (BCG) vaccine and at low risk for tuberculosis (TB) may enroll without having a TB test performed
Exclusion criteria
* Participant has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the study participant's ability to participate in this study * Participant is not permitted to enroll into the study if she meets any of the following TB
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Predose and Postdose Plasma Certolizumab Pegol (CZP) Concentrations in Women During Pregnancy, Relative to Postpartum | Predose and postdose CZP concentrations in Pregnancy trimester 1,2,3 (up to 40 weeks) and Postpartum (up to 13 weeks after delivery) | Predose and postdose plasma CZP concentrations in women during pregnancy, relative to postpartum, were measured. The trimesters were defined as follows: Trimester 1=up to 12 weeks and 6 days gestation, trimester 2=13-28 weeks and 6 days gestation, and trimester 3=any time at or after 29 weeks gestation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Anti-certolizumab Pegol (CZP) Positive Antibodies Throughout the Study Period | From Enrollment to Safety Follow-up (Duration of pregnancy (up to 40 weeks) + 18 weeks) (up to 58 weeks) | Antibodies to CZP were evaluated in plasma samples collected from all participants throughout the study. Anti-CZP antibodies (ADAb) were measured using a three-tiered assay approach: screening, confirmatory and titration assay. Samples that were confirmed as positive in the screening and confirmatory assay were evaluated in a titration assay to quantify the ADAb level and were reported as titer (reciprocal dilution factor including minimum required dilution \[MRD\]). Sample values that were 'positive screen' and 'positive immunodepletion' were defined as ADAb positive. Once determined positive, a study participant's highest titer was used to categorize (titer classification) the study participant as follows: Positive less than or equal to (=)32, Positive greater than (\>)32 - =128, Positive \>128 - =512, Positive \>512 - =1024, Positive \>1024 - =4096, and Positive \>4096. |
| Percentage of Participants With Adverse Events From Time of Informed Consent (Screening) Through Safety Follow-up (SFU) | From Screening to Safety Follow-up (Duration of pregnancy (up to 40 weeks) + 18 weeks) (up to 58 weeks) | An adverse event (AE) was any untoward medical occurrence in a patient or clinical participant, temporally associated with the use of CZP, whether or not considered related to CZP. |
| Number of Participants With Pregnancy Outcome | From Enrollment to Delivery (Duration of pregnancy, up to 40 weeks) | Pregnancy outcomes were collected via a written notification by the investigator and recorded in the Pregnancy Outcome Form. Pregnancies were determined to end in delivery-live birth, delivery-still birth, spontaneous abortion, therapeutic abortion, or missing data. |
Countries
France, Germany, Netherlands, Spain, Switzerland, United States
Participant flow
Recruitment details
The study started to enroll participants in June 2020 and concluded in May 2023.
Pre-assignment details
The Participant Flow refers to the Enrolled Set.
Participants by arm
| Arm | Count |
|---|---|
| Not Dosed This arm included participant who signed the Informed Consent Form (ICF) but withdrew from the study prior to taking a dose of commercial certolizumab pegol (CZP) after enrollment. | 0 |
| CZP 200 mg Q2W The study included pregnant women who continued treatment with commercial certolizumab pegol (CZP) in accordance with their treating physician prior to participating in the study. Study participants were responsible for obtaining and administering commercially available CZP under the care of their physician and according to the locally approved product label. Participants took commercial CZP 200 milligrams (mg) every 2 weeks (Q2W), as subcutaneous injection, during the pregnancy period (up to 40 weeks) and post-partum period (up to 13 weeks after delivery). | 15 |
| CZP 400 mg Q2W The study included pregnant women who continued treatment with commercial CZP in accordance with their treating physician prior to participating in the study. Study participants were responsible for obtaining and administering commercially available CZP under the care of their physician and according to the locally approved product label. Participants took commercial CZP 400 mg Q2W, as subcutaneous injection, during the pregnancy period (up to 40 weeks) and post-partum period (up to 13 weeks after delivery). | 0 |
| CZP 400 mg Q4W The study included pregnant women who continued treatment with commercial CZP in accordance with their treating physician prior to participating in the study. Study participants were responsible for obtaining and administering commercially available CZP under the care of their physician and according to the locally approved product label. Participants took commercial CZP 400 mg every 4 weeks (Q4W), as subcutaneous injection, during the pregnancy period (up to 40 weeks) and post-partum period (up to 13 weeks after delivery). | 5 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Enrollment | Adverse Event | 1 | 0 | 0 | 0 |
| Treatment | Adverse Event | 0 | 1 | 0 | 0 |
| Treatment | Indeterminate TB-test | 0 | 0 | 0 | 1 |
| Treatment | Participant did not want to continue in study | 0 | 0 | 0 | 1 |
| Treatment | Withdrawal by Subject | 0 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Not Dosed | CZP 200 mg Q2W | CZP 400 mg Q2W | CZP 400 mg Q4W | Total |
|---|---|---|---|---|---|
| Age, Customized 18 - <65 years | 0 Participants | 15 Participants | 0 Participants | 5 Participants | 20 Participants |
| Age, Customized 65 - <85 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >=85 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 0 Participants | 15 Participants | 0 Participants | 4 Participants | 19 Participants |
| Race/Ethnicity, Customized White | 0 Participants | 14 Participants | 0 Participants | 5 Participants | 19 Participants |
| Sex: Female, Male Female | 0 Participants | 15 Participants | 0 Participants | 5 Participants | 20 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 15 | 0 / 0 | 0 / 5 |
| other Total, other adverse events | 0 / 0 | 11 / 15 | 0 / 0 | 3 / 5 |
| serious Total, serious adverse events | 0 / 0 | 4 / 15 | 0 / 0 | 1 / 5 |
Outcome results
Primary
Predose and Postdose Plasma Certolizumab Pegol (CZP) Concentrations in Women During Pregnancy, Relative to Postpartum
Predose and postdose plasma CZP concentrations in women during pregnancy, relative to postpartum, were measured. The trimesters were defined as follows: Trimester 1=up to 12 weeks and 6 days gestation, trimester 2=13-28 weeks and 6 days gestation, and trimester 3=any time at or after 29 weeks gestation.
Time frame: Predose and postdose CZP concentrations in Pregnancy trimester 1,2,3 (up to 40 weeks) and Postpartum (up to 13 weeks after delivery)
Population: The Pharmacokinetic Per-Protocol Set (PK-PPS) was a subset of the Safety Set (SS) which included those study participants for whom at least one predose or postdose sample was available which was not impacted by an important protocol deviation. Here, number analyzed signifies participants who were evaluable at specified time points. Due to data protection/data privacy, data cannot be reported for a single participant enrolled in 'CZP 400 mg Q2W' arm.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| CZP 200 mg Q2W | Predose and Postdose Plasma Certolizumab Pegol (CZP) Concentrations in Women During Pregnancy, Relative to Postpartum | Predose-Postpartum | 22.318 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 41.1 |
| CZP 200 mg Q2W | Predose and Postdose Plasma Certolizumab Pegol (CZP) Concentrations in Women During Pregnancy, Relative to Postpartum | Predose-Trimester 1 | 15.251 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 68.1 |
| CZP 200 mg Q2W | Predose and Postdose Plasma Certolizumab Pegol (CZP) Concentrations in Women During Pregnancy, Relative to Postpartum | Postdose-Trimester 1 | 20.046 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 54.3 |
| CZP 200 mg Q2W | Predose and Postdose Plasma Certolizumab Pegol (CZP) Concentrations in Women During Pregnancy, Relative to Postpartum | Postdose-Trimester 2 | 22.961 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 44.9 |
| CZP 200 mg Q2W | Predose and Postdose Plasma Certolizumab Pegol (CZP) Concentrations in Women During Pregnancy, Relative to Postpartum | Predose-Trimester 3 | 16.827 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 41 |
| CZP 200 mg Q2W | Predose and Postdose Plasma Certolizumab Pegol (CZP) Concentrations in Women During Pregnancy, Relative to Postpartum | Postdose-Postpartum | 30.153 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 47.2 |
| CZP 200 mg Q2W | Predose and Postdose Plasma Certolizumab Pegol (CZP) Concentrations in Women During Pregnancy, Relative to Postpartum | Postdose-Trimester 3 | 25.001 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 39.7 |
| CZP 200 mg Q2W | Predose and Postdose Plasma Certolizumab Pegol (CZP) Concentrations in Women During Pregnancy, Relative to Postpartum | Predose-Trimester 2 | 16.916 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 39.9 |
| CZP 400 mg Q4W | Predose and Postdose Plasma Certolizumab Pegol (CZP) Concentrations in Women During Pregnancy, Relative to Postpartum | Postdose-Postpartum | NA microgram per milliliter (μg/mL) | — |
| CZP 400 mg Q4W | Predose and Postdose Plasma Certolizumab Pegol (CZP) Concentrations in Women During Pregnancy, Relative to Postpartum | Postdose-Trimester 3 | 8.105 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 19481.3 |
| CZP 400 mg Q4W | Predose and Postdose Plasma Certolizumab Pegol (CZP) Concentrations in Women During Pregnancy, Relative to Postpartum | Predose-Trimester 1 | NA microgram per milliliter (μg/mL) | — |
| CZP 400 mg Q4W | Predose and Postdose Plasma Certolizumab Pegol (CZP) Concentrations in Women During Pregnancy, Relative to Postpartum | Predose-Trimester 2 | 9.027 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 107.2 |
| CZP 400 mg Q4W | Predose and Postdose Plasma Certolizumab Pegol (CZP) Concentrations in Women During Pregnancy, Relative to Postpartum | Predose-Trimester 3 | 2.759 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 3193.5 |
| CZP 400 mg Q4W | Predose and Postdose Plasma Certolizumab Pegol (CZP) Concentrations in Women During Pregnancy, Relative to Postpartum | Predose-Postpartum | NA microgram per milliliter (μg/mL) | — |
| CZP 400 mg Q4W | Predose and Postdose Plasma Certolizumab Pegol (CZP) Concentrations in Women During Pregnancy, Relative to Postpartum | Postdose-Trimester 2 | 46.094 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 14.6 |
Secondary
Number of Participants With Anti-certolizumab Pegol (CZP) Positive Antibodies Throughout the Study Period
Antibodies to CZP were evaluated in plasma samples collected from all participants throughout the study. Anti-CZP antibodies (ADAb) were measured using a three-tiered assay approach: screening, confirmatory and titration assay. Samples that were confirmed as positive in the screening and confirmatory assay were evaluated in a titration assay to quantify the ADAb level and were reported as titer (reciprocal dilution factor including minimum required dilution \[MRD\]). Sample values that were 'positive screen' and 'positive immunodepletion' were defined as ADAb positive. Once determined positive, a study participant's highest titer was used to categorize (titer classification) the study participant as follows: Positive less than or equal to (=)32, Positive greater than (\>)32 - =128, Positive \>128 - =512, Positive \>512 - =1024, Positive \>1024 - =4096, and Positive \>4096.
Time frame: From Enrollment to Safety Follow-up (Duration of pregnancy (up to 40 weeks) + 18 weeks) (up to 58 weeks)
Population: The Safety Set (SS) included all enrolled study participants who received at least 1 dose of CZP after Screening. Due to data protection/data privacy, data cannot be reported for a single participant enrolled in 'CZP 400 mg Q2W' arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CZP 200 mg Q2W | Number of Participants With Anti-certolizumab Pegol (CZP) Positive Antibodies Throughout the Study Period | Positive >128 to ≤512 | 1 Participants |
| CZP 200 mg Q2W | Number of Participants With Anti-certolizumab Pegol (CZP) Positive Antibodies Throughout the Study Period | Positive >512 to ≤1024 | 0 Participants |
| CZP 200 mg Q2W | Number of Participants With Anti-certolizumab Pegol (CZP) Positive Antibodies Throughout the Study Period | Positive >1024 to ≤4096 | 5 Participants |
| CZP 200 mg Q2W | Number of Participants With Anti-certolizumab Pegol (CZP) Positive Antibodies Throughout the Study Period | Positive >32 to ≤128 | 0 Participants |
| CZP 200 mg Q2W | Number of Participants With Anti-certolizumab Pegol (CZP) Positive Antibodies Throughout the Study Period | Positive >4096 | 8 Participants |
| CZP 200 mg Q2W | Number of Participants With Anti-certolizumab Pegol (CZP) Positive Antibodies Throughout the Study Period | Positive ≤32 | 0 Participants |
| CZP 400 mg Q4W | Number of Participants With Anti-certolizumab Pegol (CZP) Positive Antibodies Throughout the Study Period | Positive >4096 | 2 Participants |
| CZP 400 mg Q4W | Number of Participants With Anti-certolizumab Pegol (CZP) Positive Antibodies Throughout the Study Period | Positive >512 to ≤1024 | 1 Participants |
| CZP 400 mg Q4W | Number of Participants With Anti-certolizumab Pegol (CZP) Positive Antibodies Throughout the Study Period | Positive ≤32 | 0 Participants |
| CZP 400 mg Q4W | Number of Participants With Anti-certolizumab Pegol (CZP) Positive Antibodies Throughout the Study Period | Positive >32 to ≤128 | 0 Participants |
| CZP 400 mg Q4W | Number of Participants With Anti-certolizumab Pegol (CZP) Positive Antibodies Throughout the Study Period | Positive >1024 to ≤4096 | 1 Participants |
| CZP 400 mg Q4W | Number of Participants With Anti-certolizumab Pegol (CZP) Positive Antibodies Throughout the Study Period | Positive >128 to ≤512 | 0 Participants |
Secondary
Number of Participants With Pregnancy Outcome
Pregnancy outcomes were collected via a written notification by the investigator and recorded in the Pregnancy Outcome Form. Pregnancies were determined to end in delivery-live birth, delivery-still birth, spontaneous abortion, therapeutic abortion, or missing data.
Time frame: From Enrollment to Delivery (Duration of pregnancy, up to 40 weeks)
Population: The Enrolled set included all participants who were confirmed as having signed the ICF to participate in the study and had provided the first blood sample. Due to data protection/data privacy, data cannot be reported for a single participant enrolled in 'Not Dosed' and 'CZP 400 mg Q2W' arms.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CZP 400 mg Q2W | Number of Participants With Pregnancy Outcome | Delivery, still birth | 0 Participants |
| CZP 400 mg Q2W | Number of Participants With Pregnancy Outcome | Therapeutic abortion | 0 Participants |
| CZP 400 mg Q2W | Number of Participants With Pregnancy Outcome | Spontaneous abortion | 0 Participants |
| CZP 400 mg Q2W | Number of Participants With Pregnancy Outcome | Missing | 3 Participants |
| CZP 400 mg Q2W | Number of Participants With Pregnancy Outcome | Delivery, live birth | 12 Participants |
| CZP 400 mg Q4W | Number of Participants With Pregnancy Outcome | Missing | 1 Participants |
| CZP 400 mg Q4W | Number of Participants With Pregnancy Outcome | Delivery, live birth | 4 Participants |
| CZP 400 mg Q4W | Number of Participants With Pregnancy Outcome | Delivery, still birth | 0 Participants |
| CZP 400 mg Q4W | Number of Participants With Pregnancy Outcome | Spontaneous abortion | 0 Participants |
| CZP 400 mg Q4W | Number of Participants With Pregnancy Outcome | Therapeutic abortion | 0 Participants |
Secondary
Percentage of Participants With Adverse Events From Time of Informed Consent (Screening) Through Safety Follow-up (SFU)
An adverse event (AE) was any untoward medical occurrence in a patient or clinical participant, temporally associated with the use of CZP, whether or not considered related to CZP.
Time frame: From Screening to Safety Follow-up (Duration of pregnancy (up to 40 weeks) + 18 weeks) (up to 58 weeks)
Population: The SS included all enrolled study participants who received at least 1 dose of CZP after Screening. Due to data protection/data privacy, data cannot be reported for a single participant enrolled in 'Not Dosed' and 'CZP 400 mg Q2W' arms.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CZP 400 mg Q2W | Percentage of Participants With Adverse Events From Time of Informed Consent (Screening) Through Safety Follow-up (SFU) | 86.7 percentage of participants |
| CZP 400 mg Q4W | Percentage of Participants With Adverse Events From Time of Informed Consent (Screening) Through Safety Follow-up (SFU) | 60.0 percentage of participants |