Back to resultsTreatment of Pregnancy RA
Primary Purpose
Rheumatoid Arthritis, Pregnancy Related
Status
Not yet recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Certolizumab Pegol 200 MG/ML [Cimzia]
Hydroxychloroquine
Prednisone
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Certolizumab, Hydroxychloroquine
Eligibility Criteria
Inclusion Criteria:
- A diagnosis of RA, as defined by 2010 ACR/EULAR criteria
- DAS 28∙ESR<2.6 under the treatment of DMARDs
- Subjects consider pregnancy, but not pregnant yet
- Participant expects to continue CZP therapy throughout pregnancy and for at least 24 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 exclusion criteria:(1) Known active TB disease; (2) History of active TB involving any organ system; (3) Latent TB infection; (4) High risk of acquiring TB infection; (5) Current nontuberculous mycobacterial (NTM) infection or history of NTM infection (unless proven to be fully recovered)
- Study participant is taking a prohibited medication or has taken a prohibited medication
- Live vaccine(s) within 1 month prior to Screening, or plans to receive such vaccines during the study
- Study participant has any clinically significant pregnancy-related clinical or test abnormality, as judged by the investigator
- Study participant had a positive or indeterminate interferon gamma release assay (IGRA) or tuberculin skin test (TST) at Screening. In case of indeterminate result, a retest is allowed if time permits; 2 results of indeterminate require exclusion of the study participant
Sites / Locations
- Renji Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
CZP
GC+HCQ
Arm Description
Certolizumab pegol: subcutaneous CZP at 200mg twice a week.
Hydroxychloroquine: HCQ at 200mg daily, and if tolerated, escalated to 400 mg daily. Glucocorticoid: continuous usage GC at 10mg a day from Week 0 to Week 52. At 24 week, non-responders (ΔDAS28<0.6) will switch to the other group. Participants switched to CZP group will taper their dose of GC gradually, if they have an improvement in disease activity (two successive DAS28<2.6). If participants have a disease flare (increased DAS28>0.6) during a reduction in corticosteroid dose, then they will resume their previous dose. Weekly step-down GC scheme: 10mg-7.5mg-5mg-2.5mg-0mg.
Outcomes
Primary Outcome Measures
Disease Activity
Proportion of DAS28 remission. In principle, the score of das28-esr should be used. If there is data missing, das28-crp can be used. All patients have either complete das28-esr data or complete das28-crp data.
Secondary Outcome Measures
ACR20
Proportion of ACR20 improvement.
ACR50
Proportion of ACR50 improvement.
ACR70
Proportion of ACR70 improvement.
Time to remission
MHAQ
The Modified Health Assessment Questionnaire (MHAQ), reduced the number of items from 20 in the original HAQ to eight, and improved the feasibility in clinical practice when screening patients. The MHAQ score is calculated as the mean of the scores for each activity. Total score is between 0.0-3.0, in 0.125 increments. Higher scores indicate worse function and greater disability. MHAQ scores <0.3 are considered normal.
EQ-5D
Health quality assessed by EuroQol five dimensions questionnaire. It is a preference-based measure that can be regarded as a continuous outcome scored on a -0.59 to 1.00 scale, with 1.00 indicating 'full health' and 0 representing dead.
Time to pregnancy
Pregnancy rate
Pregnancy outcomes
Pregnancy will end with live birth, stillbirth, spontaneous abortion or therapeutic abortion.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04569890
Brief Title
Treatment of Pregnancy RA
Official Title
Study on the Treatment Strategy of Patients With Rheumatoid Arthritis During Pregnancy, a Randomized Control Trial in China
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 1, 2020 (Anticipated)
Primary Completion Date
December 1, 2022 (Anticipated)
Study Completion Date
December 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
RenJi Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
It is important to control the disease of pregnant women with rheumatoid arthritis to ensure the fetal and maternal health. Frequent disease flare can increase the risk of adverse pregnancy outcomes, including abortion, premature delivery and low birth weight. However, there is no scientific and standardized treatment strategy for RA during pregnancy. About 50% of RA patients need treatment during pregnancy. Tumor necrosis inhibitor (TNFi) is an effective treatment, which can significantly improve the symptoms of RA during pregnancy. However, in order to avoid placental metastasis, TNFi is usually stopped in early pregnancy. Certolizumab pegol (CZP) is a PEGylated, Fc-free TNFi, which does not bind FcRn and is consequently not expected to undergo FcRn-mediated transfer across the placenta. Therefore, it can not transfer through placenta into FcRn and is approved to treat RA during pregnancy. This study focuses on patients with RA who consider pregnancy. We compared the efficacy, safety and economy of CZP and glucocorticoids combined with hydroxychloroquine by a randomized controlled trial.
Detailed Description
In this study, a randomized controlled study was conducted to compare the efficacy, safety and economy of CZP and glucocorticoids combined with hydroxychloroquine in the treatment of RA patients who consider pregnancy. Informed consent must be obtained for the patients to be screened.
Random method: central random.
Blinding method: assessor and data analyst blindness.
Follow-up: every 4 week.
First endpoint: 24 week.
Second endpoint: 52 week.
Safety endpoint: 24 weeks postpartum.
Missing data: core data related to treatment and disease activity are not allowed to be missing, and other data are supplemented by the last observation value.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis, Pregnancy Related
Keywords
Certolizumab, Hydroxychloroquine
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Central random. Statistical experts from a third-party company not involved in the study will generate a random number table by computer system. The patients will be numbered according to their visiting order, and 1:1 allocated according to the random data table.
Masking
InvestigatorOutcomes Assessor
Masking Description
Assessor and data analyst blindness. To avoid bias, physicians who assess disease activity will be blinded. Participants are required not to discuss their treatment allocation with physicians at each visit. The success of the blind method will be judged by requiring the assessors to determine the treatment allocation of participants after each visit. When the database is locked, the statistician will carry on the data analysis in the hidden of allocation.
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CZP
Arm Type
Experimental
Arm Description
Certolizumab pegol: subcutaneous CZP at 200mg twice a week.
Arm Title
GC+HCQ
Arm Type
Active Comparator
Arm Description
Hydroxychloroquine: HCQ at 200mg daily, and if tolerated, escalated to 400 mg daily.
Glucocorticoid: continuous usage GC at 10mg a day from Week 0 to Week 52.
At 24 week, non-responders (ΔDAS28<0.6) will switch to the other group. Participants switched to CZP group will taper their dose of GC gradually, if they have an improvement in disease activity (two successive DAS28<2.6). If participants have a disease flare (increased DAS28>0.6) during a reduction in corticosteroid dose, then they will resume their previous dose. Weekly step-down GC scheme: 10mg-7.5mg-5mg-2.5mg-0mg.
Intervention Type
Drug
Intervention Name(s)
Certolizumab Pegol 200 MG/ML [Cimzia]
Intervention Description
CZP 200mg twice a week subcutaneous.
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Intervention Description
400mg HCQ orally daily
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
10mg GC orally daily
Primary Outcome Measure Information:
Title
Disease Activity
Description
Proportion of DAS28 remission. In principle, the score of das28-esr should be used. If there is data missing, das28-crp can be used. All patients have either complete das28-esr data or complete das28-crp data.
Time Frame
24 week
Secondary Outcome Measure Information:
Title
ACR20
Description
Proportion of ACR20 improvement.
Time Frame
52 week
Title
ACR50
Description
Proportion of ACR50 improvement.
Time Frame
52 week
Title
ACR70
Description
Proportion of ACR70 improvement.
Time Frame
52 week
Title
Time to remission
Time Frame
52 week
Title
MHAQ
Description
The Modified Health Assessment Questionnaire (MHAQ), reduced the number of items from 20 in the original HAQ to eight, and improved the feasibility in clinical practice when screening patients. The MHAQ score is calculated as the mean of the scores for each activity. Total score is between 0.0-3.0, in 0.125 increments. Higher scores indicate worse function and greater disability. MHAQ scores <0.3 are considered normal.
Time Frame
52 week
Title
EQ-5D
Description
Health quality assessed by EuroQol five dimensions questionnaire. It is a preference-based measure that can be regarded as a continuous outcome scored on a -0.59 to 1.00 scale, with 1.00 indicating 'full health' and 0 representing dead.
Time Frame
52 week
Title
Time to pregnancy
Time Frame
52 week
Title
Pregnancy rate
Time Frame
52 week
Title
Pregnancy outcomes
Description
Pregnancy will end with live birth, stillbirth, spontaneous abortion or therapeutic abortion.
Time Frame
0-52 week
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
A diagnosis of RA, as defined by 2010 ACR/EULAR criteria
DAS 28∙ESR<2.6 under the treatment of DMARDs
Subjects consider pregnancy, but not pregnant yet
Participant expects to continue CZP therapy throughout pregnancy and for at least 24 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 exclusion criteria:(1) Known active TB disease; (2) History of active TB involving any organ system; (3) Latent TB infection; (4) High risk of acquiring TB infection; (5) Current nontuberculous mycobacterial (NTM) infection or history of NTM infection (unless proven to be fully recovered)
Study participant is taking a prohibited medication or has taken a prohibited medication
Live vaccine(s) within 1 month prior to Screening, or plans to receive such vaccines during the study
Study participant has any clinically significant pregnancy-related clinical or test abnormality, as judged by the investigator
Study participant had a positive or indeterminate interferon gamma release assay (IGRA) or tuberculin skin test (TST) at Screening. In case of indeterminate result, a retest is allowed if time permits; 2 results of indeterminate require exclusion of the study participant
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Le Zhang
Phone
+8615618296046
Email
joyce66dbl@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Liangjing Lu, doctor
Organizational Affiliation
RenJi Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Renji Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200001
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
Email the researchers for details.
Citations:
PubMed Identifier
29030361
Citation
Mariette X, Forger F, Abraham B, Flynn AD, Molto A, Flipo RM, van Tubergen A, Shaughnessy L, Simpson J, Teil M, Helmer E, Wang M, Chakravarty EF. Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study. Ann Rheum Dis. 2018 Feb;77(2):228-233. doi: 10.1136/annrheumdis-2017-212196. Epub 2017 Oct 13.
Results Reference
result
PubMed Identifier
26617214
Citation
Forger F, Zbinden A, Villiger PM. Certolizumab treatment during late pregnancy in patients with rheumatic diseases: Low drug levels in cord blood but possible risk for maternal infections. A case series of 13 patients. Joint Bone Spine. 2016 May;83(3):341-3. doi: 10.1016/j.jbspin.2015.07.004. Epub 2015 Nov 23.
Results Reference
result
PubMed Identifier
29623679
Citation
Clowse MEB, Scheuerle AE, Chambers C, Afzali A, Kimball AB, Cush JJ, Cooney M, Shaughnessy L, Vanderkelen M, Forger F. Pregnancy Outcomes After Exposure to Certolizumab Pegol: Updated Results From a Pharmacovigilance Safety Database. Arthritis Rheumatol. 2018 Sep;70(9):1399-1407. doi: 10.1002/art.40508. Epub 2018 Jul 22.
Results Reference
result
Learn more about this trial
Treatment of Pregnancy RA
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