Clinical Trial Results:
A Multicenter Postmarketing Study to Evaluate the Placental Transfer of Certolizumab Pegol in Pregnant Women Receiving Treatment with Cimzia® (Certolizumab Pegol)
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Summary
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EudraCT number |
2013-003812-30 |
Trial protocol |
NL |
Global end of trial date |
21 Nov 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
07 Dec 2017
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First version publication date |
07 Dec 2017
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
UP0017
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02019602 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
UCB BIOSCIENCES Inc.
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Sponsor organisation address |
8010 Arco Corporate Drive, Raleigh, United States, 27617
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Public contact |
Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
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Scientific contact |
Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Dec 2016
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Nov 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess whether there was transfer of Certolizumab Pegol (CZP) across the placenta to infants from mothers by evaluating the concentration of CZP in the plasma of infants at birth.
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Protection of trial subjects |
During the conduct of the study all mothers and infants were closely monitored. Additionally, for the comfort and convenience of the mother and her baby, the study allowed home healthcare nurses to perform study procedures in the mothers’ homes.
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Background therapy |
Background therapy was permitted as defined in the study protocol. | ||
Evidence for comparator |
Not applicable. | ||
Actual start date of recruitment |
09 Jan 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 7
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Country: Number of subjects enrolled |
Netherlands: 2
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Country: Number of subjects enrolled |
Switzerland: 12
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Country: Number of subjects enrolled |
United States: 16
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Worldwide total number of subjects |
37
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EEA total number of subjects |
9
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
16
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
21
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study started to enroll patients in January 2014 and concluded in November 2016. | ||||||||||||||||||
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Pre-assignment
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Screening 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. | ||||||||||||||||||
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Period 1
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Period 1 title |
Screening Period
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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SS-M | ||||||||||||||||||
Arm description |
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. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Cimzia
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Investigational medicinal product code |
CZP
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Other name |
Certolizumab pegol
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Pharmaceutical forms |
Lyophilisate for solution for injection, Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
This study only included pregnant women who started or decided to continue treatment with CZP for an approved indication in accordance with their treating physician prior to participating in the study. The CZP was not provided by the Sponsor. The CZP dose and administration schedule were per the physician’s instructions.
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Arm title
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SS-I | ||||||||||||||||||
Arm description |
This arm consisted of all infants born to mothers in the SS-M group. | ||||||||||||||||||
Arm type |
No intervention | ||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Period 2
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Period 2 title |
Sampling Period
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Is this the baseline period? |
No | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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SS-M | ||||||||||||||||||
Arm description |
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. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Cimzia
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Investigational medicinal product code |
CZP
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Other name |
Certolizumab pegol
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Pharmaceutical forms |
Solution for injection in pre-filled syringe, Lyophilisate for solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
This study only included pregnant women who started or decided to continue treatment with CZP for an approved indication in accordance with their treating physician prior to participating in the study. The CZP was not provided by the Sponsor. The CZP dose and administration schedule were per the physician’s instructions.
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Arm title
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SS-I | ||||||||||||||||||
Arm description |
This arm consisted of all infants born to mothers in the SS-M group. | ||||||||||||||||||
Arm type |
No intervention | ||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
SS-M
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Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
SS-I
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Reporting group description |
This arm consisted of all infants born to mothers in the SS-M group. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
SS-M
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Reporting group description |
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. | ||
Reporting group title |
SS-I
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Reporting group description |
This arm consisted of all infants born to mothers in the SS-M group. | ||
Reporting group title |
SS-M
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Reporting group description |
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. | ||
Reporting group title |
SS-I
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Reporting group description |
This arm consisted of all infants born to mothers in the SS-M group. | ||
Subject analysis set title |
PKS-M
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
This arm consisted of all mothers from the SS-M analysis set who provided the CZP concentration sample at delivery.
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Subject analysis set title |
PKS-U
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
This arm consisted of all umbilical cords of infants from the SS-I analysis set from which a CZP concentration sample was obtained at birth.
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Subject analysis set title |
PK-PPS-I
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
This arm consisted of all infants from the SS-I analysis set who provided a CZP concentration sample at birth and had no important protocol deviations that would have impacted the primary PK analysis.
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End point title |
The plasma concentration of Certolizumab Pegol (CZP) in the Infant(s) at birth [1] | ||||||||||
End point description |
Blood samples will be taken within 24 hours after birth from the infant(s).
-999 = below limit of quantification.
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End point type |
Primary
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End point timeframe |
Day 0
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
The plasma concentration of Certolizumab Pegol (CZP) in the mother at delivery | ||||||||||
End point description |
Blood samples will be taken within 24 hours before/after delivery from the mothers.
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End point type |
Secondary
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End point timeframe |
Day 0
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| No statistical analyses for this end point | |||||||||||
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End point title |
The ratio of plasma concentration of Certolizumab Pegol (CZP) between the infant(s) and mother at delivery/birth | ||||||||||
End point description |
Blood samples will be 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.
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End point type |
Secondary
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End point timeframe |
Day 0
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| No statistical analyses for this end point | |||||||||||
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End point title |
The plasma concentration of Certolizumab Pegol (CZP) in the umbilical cord at birth | ||||||||||
End point description |
Blood samples will be taken directly after delivery (within <= 1 hour) from the umbilical cord.
-999 = below limit of quantification.
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End point type |
Secondary
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End point timeframe |
Day 0
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| No statistical analyses for this end point | |||||||||||
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End point title |
The plasma concentration level of anti-CZP antibodies in the mother at delivery | ||||||||||
End point description |
Blood samples will be taken within 24 hours before/after delivery from the mothers.
-999 = below limit of quantification.
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End point type |
Secondary
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End point timeframe |
Day 0
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| No statistical analyses for this end point | |||||||||||
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End point title |
The plasma concentration level of anti-CZP antibodies in the umbilical cord(s) at birth | ||||||||||
End point description |
Blood samples will be taken directly after delivery (within <= 1 hour) from the umbilical cord.
-999 = below limit of quantification.
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End point type |
Secondary
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End point timeframe |
Day 0
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| No statistical analyses for this end point | |||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse Events were collected during the whole study period (from Week 0 up to Week 25)
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.1
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Reporting groups
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Reporting group title |
SS-I
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Reporting group description |
This arm consisted of all infants born to mothers in the SS-M group. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
SS-M
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Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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04 Nov 2014 |
Protocol Amendment 1, approved on 04 Nov 2014, was a substantial amendment implemented to provide clarification to aid smooth running of the study, to address inconsistencies between this study and the closely related breast milk study, UP0016, and to address some operational challenges observed or presented to UCB as feedback from Independent Ethics Committees/Institutional Review Boards and partner operations personnel, as well as Investigators and study site personnel.
The main changes included:
•Update of the text regarding the approval status for CZP, per the latest Investigator’s brochure, to include additional indications for CZP treatment – psoriatic arthritis, ankylosing spondylitis, and axial spondyloarthritis.
•Clarification of infant consent/assent.
•Clarification of the requirements for blood sampling for the infant.
•Clarification of the procedures for analysis of blood samples.
•Clarification of the noninterventional design of the study as it related to CZP therapy.
•Clarifications of tuberculosis (TB) testing requirements and procedures for subjects who developed latent TB or active TB.
•Clarification of the definitions of the analysis sets.
•Analysis of the ratios of CZP and polyethylene glycol concentrations in maternal and umbilical cord were added as exploratory pharmacokinetic variables.
•Minor changes were made for consistency with updated Sponsor document templates.
•Some changes were made based on feedback from the Swiss Ethics Committee on Protocol UP0016: addition of names and addresses of central and local laboratories, and clarification of data confidentiality regarding data anonymization and retraction of consent.
•Some changes were made in the statistical analysis sections (safety analyses and handling of protocol deviations) based on discussions during preparation of the Statistical Analysis Plan for UP0016.
•Correction of typographical errors, minor inconsistencies, and editorial updates to aid clarity. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/29030361 |
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