Treatment of Pregnancy RA

NCT04569890 | Unknown

• 1 other identifier: treatment of pregnancy RA
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Arthritis; Pregnancy Related

Keywords

Certolizumab; Hydroxychloroquine

Outcome Measures

Primary Outcomes (1)

• 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.

  24 week

Secondary Outcomes (9)

• ACR20

  52 week

• ACR50

  52 week

• ACR70

  52 week

• Time to remission

  52 week

• MHAQ

  52 week

Study Arms (2)

CZP

EXPERIMENTAL

Certolizumab pegol: subcutaneous CZP at 200mg twice a week.

Drug: Certolizumab Pegol 200 MG/ML [Cimzia]

GC+HCQ

ACTIVE COMPARATOR

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.

Drug: Hydroxychloroquine; Drug: Prednisone

Interventions

Certolizumab Pegol 200 MG/ML [Cimzia] DRUG

CZP 200mg twice a week subcutaneous.

CZP

Hydroxychloroquine DRUG

400mg HCQ orally daily

GC+HCQ

Prednisone DRUG

10mg GC orally daily

GC+HCQ

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Renji Hospital

Shanghai, Shanghai Municipality, 200001, China

Location

Related Publications (3)

• 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.

  PMID: 29030361 RESULT

• 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.

  PMID: 26617214 RESULT

• 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.

  PMID: 29623679 RESULT

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Certolizumab Pegol; Hydroxychloroquine; Prednisone

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Polyethylene Glycols; Polymers; Macromolecular Substances; Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Liangjing Lu, doctor

  RenJi Hospital

  STUDY CHAIR

Central Study Contacts

Le Zhang

CONTACT

+8615618296046; joyce66dbl@hotmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 20, 2020
• First Posted: September 30, 2020
• Study Start: December 1, 2020
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2023
• Last Updated: October 1, 2020

Record last verified: 2020-09

Locations

CN (1)