APPROVED
AS MODIFIED
May 09, 2013
WIRBâ
UCB Pharma SA
RA 0055
20120644
W120412003
Research subject information and Consent formTITLE: / A MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBOCONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF CERTOLIZUMAB PEGOL IN COMBINATION WITH METHOTREXATE FOR INDUCING AND SUSTAINING CLINICAL RESPONSE IN THE TREATMENT OF DMARD-NAÏVE ADULTS WITH EARLY ACTIVE RHEUMATOID ARTHRITIS
This consent form contains important information to help you decide whether to participate in a research study.
The study staff will explain this study to you. Ask questions about anything that is not clear at any time. You may take home an unsigned copy of this consent form to think about and discuss with family or friends.
1. Being in a study is voluntary – your choice.
2. If you join this study, you can still stop at any time.
3. No one can promise that a study will help you.
4. Do not join this study unless all of your questions are answered.
After reading and discussing the information in this consent form you should know:
Ø Why this research study is being done;
Ø What will happen during the study;
Ø Any possible benefits to you;
Ø The possible risks to you;
Ø Other options you could choose instead of being in this study;
Ø How your personal health information will be treated during the study and after the study is over;
Ø Whether being in this study could involve any cost to you; and
Ø What to do if you have problems or questions about this study.
Please read this consent form carefully.
RESEARCH SUBJECT INFORMATION AND CONSENT FORM
Title: A MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF CERTOLIZUMAB PEGOL IN COMBINATION WITH METHOTREXATE FOR INDUCING AND SUSTAINING CLINICAL RESPONSE IN THE TREATMENT OF DMARD-NAÏVE ADULTS WITH EARLY ACTIVE RHEUMATOID ARTHRITIS
Protocol No.: RA0055
WIRB® Protocol #20120644
W120412003
Sponsor: UCB Pharma SA
Investigator: Jeffrey R. Curtis, M.D., MPH
SRC 076
1717 6th Avenue South
Birmingham, Alabama 35294
United States
Site(s): University of Alabama at Birmingham
SRC 076
1717 6th Ave. South
Birmingham, Alabama 35294
United States
Study-related
Phone number(s): Jeffrey R. Curtis, M.D., MPH
205-934-7727
205-934-3411 (24 hour pager)
Informed Consent
Before agreeing to participate in this research study, it is important that you read and understand the following explanation of the proposed research study. This consent document describes the purpose, procedures, potential benefits, risks, discomforts and precautions of the study. It also describes the alternative procedures that are available to you and your right to withdraw from the study at any time. No guarantees or assurances can be made as to the results of the study. Please ask the study doctor or the study staff to explain any words or information that you do not clearly understand.
If you are not completely truthful with your study doctor regarding your health history, you may harm yourself by participating in this study.
You have been asked to participate in a research study initiated, managed, and financed by UCB Pharma S.A., the Sponsor of this study, which will be referred to in this document as “UCB”. Your study doctor is being paid by UCB Pharma S.A., to conduct this study.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.
PURPOSE OF THE STUDY
Before you decide to participate in this study, it is important for you to understand why the study is being done and what it will involve. This information sheet will provide you with essential information about this study and your rights as a study subject so that you can make an informed decision about your participation.
If you are not completely truthful with your study doctor regarding your health history, you may harm yourself by participating in this study.
Your decision to participate in this study is entirely voluntary. You will not lose any benefits to which you would otherwise be entitled if you refuse to participate. In addition, you may withdraw from the study at any time without penalty or loss of benefits to which you are otherwise entitled. You will be informed in a timely manner, if any new information about this drug or the study itself becomes available that may alter your willingness to continue to participate. If you agree for him/her to be informed, your General Practitioner/Family physician will be told that you are taking part in this study. A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.
You will be asked to participate and sign a separate informed consent for an optional Pharmacogenomics sub-study. Your decision to participate in this sub-study is entirely voluntary. You may refuse this additional research and still participate in this main RA0055 study.
You are being asked to participate in this clinical research study because you are suffering from Rheumatoid Arthritis.
The purposes and experimental aspects of this study are to investigate if starting a standard treatment with a disease-modifying anti-rheumatic drug (also known as DMARD) combined with certolizumab pegol (the active study drug) in an early stage of your illness can get you into a condition called ‘remission’ after one year of study, meaning having no or only few disease symptoms (i.e. swollen or tender joints or almost no pain). The second year of this study is intended to adapt the treatment and to investigate if a monthly treatment dosing frequency will still keep you in a ‘minimal sign and symptoms state’ compared to a biweekly (once every 2 weeks) treatment dosing. If your symptoms worsen during the study it will also be investigated if re-treatment with a bi-weekly dosing frequency can bring you back into the low disease activity state.
What is the drug being tested in this study?
Certolizumab pegol is a drug approved by the United States (US) Food and Drug Administration (FDA) for the treatment of moderate to severe active rheumatoid arthritis (RA). This research study is to determine whether certolizumab pegol can reduce the symptoms of early, progressive RA.
Certolizumab pegol is an “anti – TNF, humanized Fab′ fragment". Certolizumab pegol works by blocking an inflammatory substance in the body that is called tumor necrosis factor (TNF). “Humanized Fab′” means that it has been engineered to act like a piece of a specific antibody from a human cell. This helps it bind to its target.
This study will involve a total of 800 subjects across approximately 200 centers throughout Europe, Australia and North- and South-America.
A table of tests, procedures and the visit schedule required for subjects who participate in this study can be found at the end of this section (see Visit Schedule below).
Study duration:
This study can last up to 116 weeks (2 years and 3 months) but may be shorter in case you do not improve sufficiently or not at all. In that case your doctor may look for other treatments outside the study to help you.
PROCEDURES
Screening Visit:
During your first visit you will receive all needed details on the study and you are free to ask any type of questions to allow you to evaluate your interest in this study. If you agree to participate in the study, your study doctor will evaluate your disease as well as review the study entry criteria to ensure you fulfill all requirements to enter the study. You will be asked to fill out questionnaires and undergo a number of tests (as described on the Visit Schedule), including a pregnancy test; ECG (electrical tracing of heart activity); x-rays of chest, hands, wrists, and feet; tests for tuberculosis (TB) and hepatitis (state law requires that the results of positive tests for hepatitis and TB be reported to a local health agency); and laboratory tests on blood samples.
This screening period can last 2-4 weeks.
First study year: Week 0 to Week 52:
During the first year there will be two groups;
· One active study medication group (receiving certolizumab pegol in addition to methotrexate) and
· One control group receiving placebo in addition to methotrexate (MTX). Placebo is an inactive substance that looks identical to the active medication.
You will receive either certolizumab pegol or placebo in pre-filled syringes. The study drug (certolizumab or placebo) must be taken by subcutaneous (sc) injection (meaning just under the skin) as follows:
· 400mg at Weeks 0, 2 and 4, followed by
· 200mg every two weeks until Week 50.
The subcutaneous injections can be given in the lateral abdominal wall (the side of your abdomen), the upper outer part of your thigh or the upper arm.
You will also receive MTX in tablet form and will have to take it on a weekly basis on the same day of the week from Week 0 onward every week until Week 51. The MTX doses will not change within the different treatment groups.
The weekly dosage of MTX will be selected and maintained according to your study doctor’s clinical judgment, but should not be less than 10mg nor higher than 25mg per week at any period of the study. The recommended starting dose is 10mg per week, the maximum tolerated MTX dosage will be achieved by Week 8. You may fall back to the lower dosage in case of tolerability problems; however you must be able to tolerate at least 10mg MTX weekly to remain in the study.
You will be randomly assigned to one of the groups with a chance of 75% to be in certolizumab pegol with methotrexate group and 25% in placebo with methotrexate group.
Your assignment to one of the two groups will be done randomly (by chance) through a phone call to a central computer system. As you will be participating in a double-blind study, your study doctor, any of the study staff (with exception of the nurse providing you the study medication) and yourself will not know which treatment group you belong to. However in case of emergency, this information will be immediately available to your study doctor.
You will visit the study site for a physical exam and other assessments about 7 times during the first 20 weeks of taking the study drugs (see the Visit Schedule below).
Your study participation will end if:
· Your condition has not improved at all by Visit 8 on Week 20 (5 months after study treatment started), or
· You have not had sufficient improvement at Week 24, or
· You did not reach the state of sustained low disease activity at Week 52.
The definitions of “sufficient improvement” and of “low disease activity” are based on carefully defined combinations of the number of swollen, tender joints, blood test results, and the subject’s own assessment of how they feel.
If your study participation ends at any of these times, you will be asked to come back for the Week 52 study visit.
Whenever your study participation ends, you should discuss other treatment options with your doctor.
If your condition has improved at Week 52 and you have been in low disease activity for at least 3 months, the following options are possible:
· If during the first year you were in the placebo + methotrexate group, in that case you will continue to the same treatment when entering the second study year.
· If during the first year you were in the study drug + methotrexate group, in that case you will be randomly assigned to one of three treatment arms (see below) when entering the second study year.
Second study year: Week 52 to Week 104:
If you continue into the second year, you will be randomly assigned to one of three treatment groups:
· One active medication group (receiving 1 subcutaneous injection of 200mg certolizumab pegol every 2 weeks in addition to methotrexate), or
· Another active medication group (receiving 1 subcutaneous injection of 200mg certolizumab pegol every 4 weeks in addition to methotrexate), or
· The third group will receive placebo in addition to methotrexate.
You will have about a 7 out of 10 chance to be in one of the groups receiving certolizumab pegol with methotrexate group and about a 3 out of 10 chance to be in the group receiving placebo with methotrexate. Your assignment to one of the three groups will also be done randomly via a computer system (see first study year).
If during the second year your condition worsens, meaning you have an increased disease activity and you are not in low disease activity anymore, you may address this worsening at any time to your doctor, not only during the study visits but also with a call to your study physician who will organize an additional visit to examine you. If the worsening of your condition is confirmed during a second visit two weeks later, you will receive certolizumab pegol until the end of the study (last treatment at week 102).