Rheumatoid ArthritisPhase 2RICENCT02293590
RICE: Remission by Intra-articular Injection Plus CErtolizumab
A Phase 2 study testing Certolizumab Pegol in people with Rheumatoid Arthritis, run by Rüdiger B. Müller at 1 site in Switzerland.
Trial summary
Tight control of an adaptive concomitant treatment strategy after initiation of CZP will lead to an improved outcome of RA patients with an active disease despite DMARD treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Certolizumab Pegol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteSwitzerland
- Study dates
- Nov 2013to 15 Jan 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects aged 18 years or older at the time of consent
- Able to give informed consent
- Patients diagnosed as having established and active rheumatoid arthritis classified according to the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) criteria (Aletaha D et al 2010) for a period of ≥ 3 months counting from the first DMARD treatment initiated. Active rheumatoid arthritis is characterised as all of the following:
- ≥6 tender joint out of the 68 joint count
- ≥6 swollen joints out of the 66 joint count
- ESR ≥ 20mm/h or CRP ≥7mg/l
Show all 12Show fewer
- Has a been found to be intolerant to, or had an inadequate clinical response to at least 1 DMARD
- Is currently being treated with DMARDs for ≥ 12 weeks and has reached a stable dose for ≥ 4 weeks.
- Is currently receiving a corticosteroid (e.g. prednisolone or equivalent) and has reached a stable dose of ≤ 10mg/d for ≥ 4 weeks (patients without current corticosteroid treatment for ≥ 4 weeks may also be included.
- Available for the whole duration of the study.
- Female subjects of childbearing potential must use maximally effective birth control during the period of therapy, must be willing to use contraception for the duration of the study (starting from randomisation and ending up to Week 24 at Day 168/Safety follow-up visit). Must have a negative pregnancy test upon entry into the study. Otherwise, female subjects must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile.
- Male subjects must be surgically sterile or willing to use a double barrier contraception method upon enrolment, for the duration of the study (starting from randomisation and ending up to Week 24 at Day 168/Safety follow-up visit).
Who cannot join
- Pregnant or breastfeeding women or such with a child-bearing potential who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for the entire study period (up to Week 24 at Day 168/Safety follow-up visit)
- Subjects with a history of cancer in the last 5 years, or with a current screening suspicious for cancer, other than non-melanoma skin cell cancers cured by local resection or carcinoma in situ
- Subjects with evidence of untreated, active or latent bacterial (e.g. tuberculosis) or viral infections (e.g. Human Immunodeficiency Virus (HIV), Hepatitis B or C) at the time of potential enrolment
- Subjects with any serious bacterial infection within the last 3 months, unless treated and resolved with antibiotics, or any untreated, chronic bacterial infection
- Having participated in another drug or an interventional study within 30 days preceding the present study screening
- Any previous treatment with CZP
- Any previous treatment with a biological DMARD
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Kantonsspital St. Gallen
Sankt Gallen, Canton of St. Gallen, 9007
About this study
Official title: An Open Label, Randomised Study to Compare the Efficacy of Certolizumab Pegol (CZP) Plus a Dynamic or Fixed Dose Treatment Strategy in Patients With Rheumatoid Arthritis, a Phase II Study
Tight control of an adaptive concomitant treatment strategy after initiation of CZP will lead to an improved outcome of RA patients with an active disease despite DMARD treatment.
Read the detailed description
Certolizumab pegol (CZP) is a tumor necrosis factor (TNF) antagonist which is marketed for the treatment of moderate to severe rheumatoid arthritis (RA) (Keystone, 2008) when given in combination with methotrexate (MTX). CZP is a PEGylated Fab' fragment of humanized anti-TNF antibody with a high affinity for TNF.
RA is a chronic inflammatory autoimmune disease with multiple treatment strategies and combination therapies available including analgesia, anti-inflammatory drugs and disease-modifying anti-rheumatic drugs. Previous trials have demonstrated positive results from the use of CZP but have compared its use to placebo in a fixed dose concomitant medication regime rather than using a more realistic dynamic treatment strategy normally employed in the clinical outpatient care of RA.
This trial is aimed at comparing the use of CZP in patients with moderate to severe RA when administered in conjunction with an intensive, adapted treatment strategy (Group A) versus a fixed-dosed program (Group B). CZP will be given in conjunction with MTX (a disease modifying anti-arthritic drug - or DMARD), steroidal therapy in the form of prednisolone and joint infiltrations of triamcinolone (another corticosteroid) and lidocaine (a pain therapy). Both treatment arms will include these concomitant medications but there will be an intensive adaptive approach adopted for the 'treat to target' population of Group A with a more fixed-dose approach set-out for Group B. Patients will be centrally randomized after screening to ensure a 50:50 ratio for both Groups in the study.
STUDY HYPOTHESIS
Tight control of an adaptive concomitant treatment strategy after initiation of CZP will lead to an improved outcome of RA patients with an active disease despite DMARD treatment.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Certolizumab Pegol
- Keywords
- Certolizumab pegol, DMARD, Joint injection, Glucocorticoids
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Certolizumab PegolDrug
Also called Cimcia, Methoject, Lederlon, Leflunomid Gebro
| Study group | Role | What they receive |
|---|---|---|
| intensive, adapted treatment strategy | Experimental | Experimental: intensive, adapted treatment strategy Certolizumab pegol (CZP, Cimzia (R)): 200mg every 2 weeks after loading d 400mg at Weeks 0, 2 and 4
DMARD:
Patients without sufficient treatment response will be taken to the next step according to the therapeutic algorithm or next drug, for example: 15=>25mg Metoject (R)/week => Leflunomide Gebro (R)20mg/d => Salazopyrine EN(R) 2000mg/d
Glucocorticoids:
At Week, 0 patients will be initiated on Spiricort (R) 20mg/d and tapered every 5 days
Joint injections:
Starting at Week 0 up to 5 joint injections may be conducted into synovitic joints at every visit of the study.
The maximum cumulative Lederlon (R) dose is 100mg/visit. Joints are to be infiltrated with the following doses of triamcinolone and lidocaine Receives: Drug: Certolizumab Pegol |
| fixed-dosed program | Active comparator | Intervention:
Certolizumab pegol (Cimzia (R), CZP) CZP of 400mg at Weeks 0, 2 and 4, followed by 200mg injections from Week 6, every 2 weeks until Week 24.
DMARD:
Patients are to continue to receive their stable weekly dose of DMARD as noted at study entry for the duration of the study (24 weeks)
Glucocorticoids:
Prednisolone (Spiricort (R)) daily dose of ≤ 10 mg
Joint injections:
None Receives: Drug: Certolizumab Pegol |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the percentage of study participants achieving American College of Rheumatology 50% (ACR50) clinical response by the Week 24 assessments
Efficacy rates as measured by the percentage of study participants achieving American College of Rheumatology 50% (ACR50) clinical response by the Week 24
Measured: 24 weeks
Secondary outcomes (7)
To compare the efficacy rates of CZP between the two treatment groups following 8, 12, 18 and 24 weeks of treatment
Efficacy rates as measured by ACR20/50/70 at weeks 8, 12, 18 and 24 weeks to determine the % of treatment responders in each study Group over the study period.
Measured: 8, 12, 18 and 24 weeks
To compare the proportion of patients reaching either a low disease activity status (LDAS) or a full remission of their RA across both treatment groups at weeks 8, 12, 18 and 24
Efficacy rates as measured by patients achieving Low DAS is defined (LDAS) or a full clinical remission according to the EULAR at weeks 8, 12, 18 and 24 weeks. LDAS as a DAS-28 score of less than 3.2. The DAS-28 is defined by the number of tender and swollen joints calculated from 28 joints mainly from the upper limbs, the ESR and the patient's global assessment of disease activity.
Remission will be defined as a DAS-28 score of less than 2.6 and/or according to the Boolean definition of remission (Felson 2011): swollen joint count, tender joint count, patients' global assessment of disease activity, CRP (mg/dl) all ≤1*
Measured: weeks 8, 12, 18 and 24
To compare the relative time taken for patients to reach remission across the two treatment groups
Efficacy rates as measured by the average number of weeks of treatment required for patients to reach remission of their RA. Clinical remission to be evaluated via the EULAR and DAS-remission criteria
Measured: weeks 8, 12, 18 and 24
To compare the cumulative corticosteroid dose for patients across the two study treatment groups following 24 weeks of treatment
Efficacy as calculated of the cumulative corticosteroid dose for patients completing the 24 week study period across the two treatment groupsCalculation of the cumulative corticosteroid dose for patients completing the 24 week study period across the two treatment groups
Measured: 24 weeks
To compare the safety and tolerability of CZP between the two treatment groups following 8, 12, 18 and 24 weeks of treatment
Safety as calculated by the occurrence of treatment emergent adverse event (TEAE, adverse events occurring after baseline of the study) across the two treatment groups
Measured: 8, 12, 18 and 24 weeks
To conduct pharmacokinetic analysis to compare the CZP serum levels following 24 weeks of treatment across both of the treatment groups
Efficacy analysis as analysed by a pharmacokinetic assessments are to be conducted at Visit 3/week 4 (day 28) and visit 7/Week 24 (Day 168 post initiation of CZP treatment)
Measured: 24 weeks
To compare the development of anti-CZP antibodies following 24 weeks of treatment across both of the treatment groups
Efficacy analysis as analysed two single timepoint anti-CZP antibody assessments are to be conducted at Visit 2/Week 0 and Visit 7/Week 24 (Day 168 post initiation of CZP treatment)
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2014 (estimated)
- Study startNov 2013
- Primary completion22 Dec 2017
- Study completion15 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rüdiger B. Müller
- Sponsor type
- University, hospital or other
- Collaborators
- UCB Pharma
- Responsible party
- Sponsor-investigator, Rüdiger B. Müller, Cantonal Hospital of St. Gallen
- Investigators
- Rueediger B Mueller, MD, Study chair, Cantonal Hospital of St. Gallen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02293590
- Sponsor's protocol ID
- EKSG13/104/2B
- Acronym
- RICE
- Status last verified
- Aug 2018
- First submitted
- 30 Oct 2014
- Last updated
- 3 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Randomised Study to Compare the Efficacy of Certolizumab Pegol (CZP) Plus a Dynamic or Fixed Dose Treatment Strategy in Patients With Rheumatoid Arthritis, a Phase II Study
- ClinicalTrials.gov ID
- NCT02293590
- Acronym / sponsor ID
- RICE / EKSG13/104/2B
- Conditions
- Rheumatoid Arthritis
- Keywords
- Certolizumab pegol, DMARD, Joint injection, Glucocorticoids
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Rüdiger B. MüllerUniversity, hospital or other
- Collaborators
- UCB Pharma
- Study start
- Nov 2013 (actual)
- Primary completion
- 22 Dec 2017 (actual)
- Study completion
- 15 Jan 2018 (actual)
- First posted
- 18 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Tight control of an adaptive concomitant treatment strategy after initiation of CZP will lead to an improved outcome of RA patients with an active disease despite DMARD treatment.
Detailed description
Certolizumab pegol (CZP) is a tumor necrosis factor (TNF) antagonist which is marketed for the treatment of moderate to severe rheumatoid arthritis (RA) (Keystone, 2008) when given in combination with methotrexate (MTX). CZP is a PEGylated Fab' fragment of humanized anti-TNF antibody with a high affinity for TNF.
RA is a chronic inflammatory autoimmune disease with multiple treatment strategies and combination therapies available including analgesia, anti-inflammatory drugs and disease-modifying anti-rheumatic drugs. Previous trials have demonstrated positive results from the use of CZP but have compared its use to placebo in a fixed dose concomitant medication regime rather than using a more realistic dynamic treatment strategy normally employed in the clinical outpatient care of RA.
This trial is aimed at comparing the use of CZP in patients with moderate to severe RA when administered in conjunction with an intensive, adapted treatment strategy (Group A) versus a fixed-dosed program (Group B). CZP will be given in conjunction with MTX (a disease modifying anti-arthritic drug - or DMARD), steroidal therapy in the form of prednisolone and joint infiltrations of triamcinolone (another corticosteroid) and lidocaine (a pain therapy). Both treatment arms will include these concomitant medications but there will be an intensive adaptive approach adopted for the 'treat to target' population of Group A with a more fixed-dose approach set-out for Group B. Patients will be centrally randomized after screening to ensure a 50:50 ratio for both Groups in the study.
STUDY HYPOTHESIS
Tight control of an adaptive concomitant treatment strategy after initiation of CZP will lead to an improved outcome of RA patients with an active disease despite DMARD treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| intensive, adapted treatment strategy | Experimental | Drug: Certolizumab PegolExperimental: intensive, adapted treatment strategy Certolizumab pegol (CZP, Cimzia (R)): 200mg every 2 weeks after loading d 400mg at Weeks 0, 2 and 4 DMARD: Patients without sufficient treatment response will be taken to the next step according to the therapeutic algorithm or next drug, for example: 15=>25mg Metoject (R)/week => Leflunomide Gebro (R)20mg/d => Salazopyrine EN(R) 2000mg/d Glucocorticoids: At Week, 0 patients will be initiated on Spiricort (R) 20mg/d and tapered every 5 days Joint injections: Starting at Week 0 up to 5 joint injections may be conducted into synovitic joints at every visit of the study. The maximum cumulative Lederlon (R) dose is 100mg/visit. Joints are to be infiltrated with the following doses of triamcinolone and lidocaine |
| fixed-dosed program | Active comparator | Drug: Certolizumab PegolIntervention: Certolizumab pegol (Cimzia (R), CZP) CZP of 400mg at Weeks 0, 2 and 4, followed by 200mg injections from Week 6, every 2 weeks until Week 24. DMARD: Patients are to continue to receive their stable weekly dose of DMARD as noted at study entry for the duration of the study (24 weeks) Glucocorticoids: Prednisolone (Spiricort (R)) daily dose of ≤ 10 mg Joint injections: None |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Male or female subjects aged 18 years or older at the time of consent
- Able to give informed consent
- Patients diagnosed as having established and active rheumatoid arthritis classified according to the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) criteria (Aletaha D et al 2010) for a period of ≥ 3 months counting from the first DMARD treatment initiated. Active rheumatoid arthritis is characterised as all of the following:
- Has a been found to be intolerant to, or had an inadequate clinical response to at least 1 DMARD
- Is currently being treated with DMARDs for ≥ 12 weeks and has reached a stable dose for ≥ 4 weeks.
Key exclusion criteria (7 listed)
- Pregnant or breastfeeding women or such with a child-bearing potential who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for the entire study period (up to Week 24 at Day 168/Safety follow-up visit)
- Subjects with a history of cancer in the last 5 years, or with a current screening suspicious for cancer, other than non-melanoma skin cell cancers cured by local resection or carcinoma in situ
- Subjects with evidence of untreated, active or latent bacterial (e.g. tuberculosis) or viral infections (e.g. Human Immunodeficiency Virus (HIV), Hepatitis B or C) at the time of potential enrolment
- Subjects with any serious bacterial infection within the last 3 months, unless treated and resolved with antibiotics, or any untreated, chronic bacterial infection
- Having participated in another drug or an interventional study within 30 days preceding the present study screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Certolizumab PegolAlso: Cimcia, Methoject, Lederlon, Leflunomid Gebro | Drug | fixed-dosed program, intensive, adapted treatment strategy |
Primary outcome
To assess the percentage of study participants achieving American College of Rheumatology 50% (ACR50) clinical response by the Week 24 assessments
Time frame: 24 weeks
Efficacy rates as measured by the percentage of study participants achieving American College of Rheumatology 50% (ACR50) clinical response by the Week 24
7 secondary outcomes
To compare the efficacy rates of CZP between the two treatment groups following 8, 12, 18 and 24 weeks of treatment
Time frame: 8, 12, 18 and 24 weeks
To compare the proportion of patients reaching either a low disease activity status (LDAS) or a full remission of their RA across both treatment groups at weeks 8, 12, 18 and 24
Time frame: weeks 8, 12, 18 and 24
To compare the relative time taken for patients to reach remission across the two treatment groups
Time frame: weeks 8, 12, 18 and 24
To compare the cumulative corticosteroid dose for patients across the two study treatment groups following 24 weeks of treatment
Time frame: 24 weeks
To compare the safety and tolerability of CZP between the two treatment groups following 8, 12, 18 and 24 weeks of treatment
Time frame: 8, 12, 18 and 24 weeks
To conduct pharmacokinetic analysis to compare the CZP serum levels following 24 weeks of treatment across both of the treatment groups
Time frame: 24 weeks
To compare the development of anti-CZP antibodies following 24 weeks of treatment across both of the treatment groups
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rueediger B Mueller, MD study chair
Cantonal Hospital of St. Gallen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Certolizumab Pegol in people with Rheumatoid Arthritis, run by Rüdiger B. Müller at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the percentage of study participants achieving American College of Rheumatology 50% (ACR50) clinical response by the Week 24 assessments (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2018.