Rheumatoid ArthritisPhase 4NCT01638715
A Randomized, Multi-Center Biomarker Trial to Predict Therapeutic Responses of Patients With Rheumatoid Arthritis to a Specific Biologic Mode of Action
A Phase 4 study testing Remicade, Orencia and Ro-Actemra in people with Rheumatoid Arthritis, run by Medical University of Vienna at 9 sites in 4 countries.
Trial summary
The purpose of this study is to find biological response patterns of patients with rheumatoid arthritis to drugs with different biologic modes of action. This study should help to predict therapeutic responses and to find the right therapy for the right patient. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Remicade, Orencia and Ro-Actemra
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 115 participants
- Where
- 9 sitesin 4 countries
- Study dates
- May 2012to 1 Aug 2018
- Phase
- Phase 4
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women, ≥18 and ≤75 years of age, capable of understanding and signing an informed consent.
- Classifiable RA according to the 2010 ACR/EULAR criteria (American College of Rheumatology/European League Against Rheumatism classification criteria) or 1987 ARA criteria (Criteria of American Rheumatology Association) (present or past) (2;3)
- Duration of RA ≤3 years
- Ongoing conventional DMARD therapy (Disease Modifying Antirheumatic Drugs) with methotrexate (at least 20mg/week, or lower if not tolerated in higher doses) or leflunomide (≥100mg/week), for ≥6 months or ≥3 months with documented worsening of disease activity.
- Clinical Disease Activity Index (CDAI)≥15 corresponding to moderate to severe disease activity.
Who cannot join
- Be incapacitated, largely or wholly bedridden, or confined to a wheelchair, or have little or no ability for self care.
- Weigh more than 100 kg
- Use glucocorticoids >10 mg/day prednisone or equivalent
- Have previously received other treatments for their rheumatic disease:
- intra-muscular or intra-articular injection of steroids in the previous month.
- monoclonal antibodies or antibody fragments, licenced or investigational
Show all 26Show fewer
- any investigational drug within 3 months prior to screening or within 5 half-lives of the investigational agent, whichever is longer.
- Azathioprine or other cytostatic drugs.
- Have a history of receiving human/murine recombinant products or a known allergy to murine products.
- Have documentation of seropositivity for human immunodeficiency virus (HIV), or a positive test for hepatitis B surface antigen or hepatitis C ¬antibodies.
- Have hypergammaglobulinemia
- Have a history of alcohol or substance abuse within the preceding 6 months.
- Have or have had a known history of
- serious infections (such as, but not limited to hepatitis, pneumonia, or pyelonephritis) in the previous 3 months.
- opportunistic infections (eg, herpes zoster, cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 12 months prior to screening.
- a chronic or recurrent infectious disease (eg, chronic renal infection, chronic chest infection, COPD, sinusitis, recurrent urinary tract infection, open, draining or infected skin wound or ulcer etc.).
- Have undergone any joint replacement surgery.
- Be men and women of childbearing potential without use of adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilization), and willingness to continue this precaution for the duration of the study until 6 months after receiving the last medication.
- Be considered ineligible according to the tuberculosis (TB) eligibility assessment and screening, or show a positive test for latent Tbc using Quantiferon assay, unless treatment with INH has been installed for at least 2 weeks prior to starting trial drug.
- Show evidence of malignancy, or lymphoproliferative disease, or any history of malignancy within the previous 5 years, with the exception of basal cell or squamous cell carcinoma of the skin that has been fully excised with no evidence of recurrence.
- Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease.
- Be unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access.
- Have presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to screening).
- Have a concomitant diagnosis or history of congestive heart failure (New York Heart Association - NYHA - class III or IV) or diverticulitis.
- Have a known history of a demyelinating disease, such as multiple sclerosis.
- Be women who are pregnant, nursing, or planning pregnancy within 6 months after the last infusion
Trial locations and contacts
9 sites in 4 countries.
9 sites in 4 countries
Austria6 sites
Gesundheitszentrum Mariahilf
Vienna, 1060
AKH Wien
Vienna, 1090
Krankenhaus Hietzing
Vienna, 1130
Hanusch Krankenhaus
Vienna, 1140
Wilhelminenspital
Vienna, 1160
Ordination Wels (Private Medical Office)
Wels, 4600
Switzerland1 site
Kantonsspital St.Gallen, Klinik für Rheumatologie
Sankt Gallen, 9007
About this study
The purpose of this study is to find biological response patterns of patients with rheumatoid arthritis to drugs with different biologic modes of action. This study should help to predict therapeutic responses and to find the right therapy for the right patient.
Read the detailed description
The investigators propose a randomised, multi-centre strategic biomarker trial of rheumatoid arthritis (RA) patients with failure to methotrexate or leflunomide to one of the four current biological modes of action: targeting TNF (infliximab); co-stimulation (abatacept); IL-6R (tocilizumab); and B cells (rituximab); all agents are licensed for RA and have evidence for efficacy in this indication. Predictors of response to therapy after 24 weeks will be analysed, and include baseline and follow up assessments of clinical, functional, structural, laboratory tests (routine, autoantibodies, cytokines, gene expression, and susceptibility genes). In a second phase, patients not achieving LDA/REM will be randomised to one of the remaining MoA. Two hundred patients, who are started on a new biological therapy will be enrolled over an estimated period of 5 years; 50 patients per group will be included, and studied for a period of 12 months.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Remicade, Orencia, Ro-Actemra, Mabthera
- Keywords
- Rheumatoid Arthritis, Biologic therapies, Biomarker, Mode of Action
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RemicadeDrug
- Infliximab (Remicade®) will be administered i.v. at a dose of 3 mg/kg at 0 and 2 weeks, and 5 mg/kg at weeks 6, 14, and 22, 30, 38, and 46.
OrenciaDrug
- Abatacept (Orencia®) will be given i.v. at weeks 0, 2, 4, and then every 4 weeks until week 48 at a weight adjusted dose: <60 kg Body weight (BW): 500 mg; >60-100 kg BW: 750 mg; alternatively, based on preference and shared decision between patient and physician, patients randomized to the abatacept arm may receive s.c. application at a dose of 125mg weekly.
Ro-ActemraDrug
- Tocilizumab (Ro-Actemra®) will be administered every 4 weeks at a dose of 8 mg/kg BW (maximum dose of 800 mg); The employed dosage will be calculated using manufacturer guidelines; alternatively, based on preference and shared decision between patient and physician, patients randomized to the tocilizumab arm may receive s.c. application at a dose of 162mg every week.
MabtheraDrug
- Rituximab (Mabthera®) will be given as 1000mg at weeks 0 and 2, and then repeated at weeks 24 and 26.
Patients will receive 100 mg methylprednisolon i.v. before each infusion, as well as 1000mg paracetamol, as well as 50mg diphenhydramine hydrochloride (Dibondrin©).
| Study group | Role | What they receive |
|---|---|---|
| Infliximab | Experimental | Infliximab (Remicade®) will be administered i.v.at a dose of 3 mg/kg at 0 and 2 weeks, and 5 mg/kg at weeks 6, 14, and 22, 30, 38, and 46. Receives: Drug: Remicade |
| Abatacept | Experimental | Abatacept (Orencia®) will be given i.v. at weeks 0, 2, 4, and then every 4 weeks until week 48 at a weight adjusted dose: <60 kg Body weight (BW): 500 mg; >60-100 kg BW: 750 mg; alternatively, based on preference and shared decision between patient and physician, patients randomized to the abatacept arm may receive s.c.application at a dose of 125mg weekly. Receives: Drug: Orencia |
| Tocilizumab | Experimental | Tocilizumab (Ro-Actemra®) will be administered every 4 weeks at a dose of 8 mg/kg BW (maximum dose of 800 mg); The employed dosage will be calculated using manufacturer guidelines; alternatively, based on preference and shared decision between patient and physician, patients randomized to the tocilizumab arm may receive s.c. application at a dose of 162mg every week. Receives: Drug: Ro-Actemra |
| Rituximab | Experimental | Rituximab (Mabthera®) will be given as 1000mg at weeks 0 and 2, and then repeated at weeks 24 and 26. Patients will receive 100 mg methylprednisolon i.v. before each infusion, as well as 1000mg paracetamol, as well as 50mg diphenhydramine hydrochloride (Dibondrin©). Receives: Drug: Mabthera |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute Change in the Simplified Disease Activity Index (SDAI)
Measured: 24 Weeks
Secondary outcomes (13)
Relative Change in the SDAI in percent
Measured: 24 Weeks
Absolute and relative change in the Clinical Disease Activity Index (CDAI) in percent
Measured: 24 Weeks
Absolute and relative change in the Disease Activity Score 28 (DAS28) in percent
Measured: 24 weeks
Achieving an SDAI or CDAI response (50%, 70%, 85%)
Measured: 24 Weeks
Achieving a EULAR response (European League Against Rheumatism)
Measured: 24 Weeks
Achieving an ACR response (20%, 50%, 70%) (American College of Rheumatology)
Measured: 24 Weeks
Change in quality of life (EuroQoL-5D, SF-36)
Measured: 24 weeks
Change in fatigue (Fatigue Score on the Visual Analog Scale)
Measured: 24 Weeks
Proportion achieving a low disease activity state (SDAI ≤11)
Measured: 24 Weeks
Proportion achieving a remission state (SDAI ≤3.3)
Measured: 24 Weeks
Radiographic progression - (Van der Heijde/Sharp Score)
Measured: 6 months and 12 months
Change in physical function (HAQ)
Measured: 24 Weeks
Change in sleep (Sleep Score on the Visual Analog Scale)
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 posted12 Jul 2012 (estimated)
- Study startMay 2012
- Primary completion1 Aug 2018
- Study completion1 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 115 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniel Aletaha, Medical University of Vienna
- Investigators
- Daniel Aletaha, MD, Study director, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01638715
- Sponsor's protocol ID
- BIOBIO Study
- Other IDs
- 2012-000139-21
- Status last verified
- Oct 2018
- First submitted
- 3 Jul 2012
- Last updated
- 31 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Studenic P, Bond G, Kerschbaumer A, Becede M, Pavelka K, Karateev D, Stieger J, Puchner R, Mueller RB, Puchhammer-Stockl E, Durechova M, Loiskandl M, Perkmann T, Olejarova M, Luchikhina E, Steiner CW, Bonelli M, Smolen JS, Aletaha D. Torque Teno Virus quantification for monitoring of immunomodulation with biologic compounds in the treatment of rheumatoid arthritis. Rheumatology (Oxford). 2022 Jul 6;61(7):2815-2825. doi: 10.1093/rheumatology/keab839.
PubMed 34792562
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Multi-Center Biomarker Trial to Predict Therapeutic Responses of Patients With Rheumatoid Arthritis to a Specific Biologic Mode of Action
- ClinicalTrials.gov ID
- NCT01638715
- Acronym / sponsor ID
- BIOBIO Study
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid Arthritis, Biologic therapies, Biomarker, Mode of Action
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 115 participants (actual)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- May 2012
- Primary completion
- 1 Aug 2018 (actual)
- Study completion
- 1 Aug 2018 (actual)
- First posted
- 12 Jul 2012 (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.
The purpose of this study is to find biological response patterns of patients with rheumatoid arthritis to drugs with different biologic modes of action. This study should help to predict therapeutic responses and to find the right therapy for the right patient.
Detailed description
The investigators propose a randomised, multi-centre strategic biomarker trial of rheumatoid arthritis (RA) patients with failure to methotrexate or leflunomide to one of the four current biological modes of action: targeting TNF (infliximab); co-stimulation (abatacept); IL-6R (tocilizumab); and B cells (rituximab); all agents are licensed for RA and have evidence for efficacy in this indication. Predictors of response to therapy after 24 weeks will be analysed, and include baseline and follow up assessments of clinical, functional, structural, laboratory tests (routine, autoantibodies, cytokines, gene expression, and susceptibility genes). In a second phase, patients not achieving LDA/REM will be randomised to one of the remaining MoA. Two hundred patients, who are started on a new biological therapy will be enrolled over an estimated period of 5 years; 50 patients per group will be included, and studied for a period of 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Infliximab | Experimental | Drug: RemicadeInfliximab (Remicade®) will be administered i.v.at a dose of 3 mg/kg at 0 and 2 weeks, and 5 mg/kg at weeks 6, 14, and 22, 30, 38, and 46. |
| Abatacept | Experimental | Drug: OrenciaAbatacept (Orencia®) will be given i.v. at weeks 0, 2, 4, and then every 4 weeks until week 48 at a weight adjusted dose: <60 kg Body weight (BW): 500 mg; >60-100 kg BW: 750 mg; alternatively, based on preference and shared decision between patient and physician, patients randomized to the abatacept arm may receive s.c.application at a dose of 125mg weekly. |
| Tocilizumab | Experimental | Drug: Ro-ActemraTocilizumab (Ro-Actemra®) will be administered every 4 weeks at a dose of 8 mg/kg BW (maximum dose of 800 mg); The employed dosage will be calculated using manufacturer guidelines; alternatively, based on preference and shared decision between patient and physician, patients randomized to the tocilizumab arm may receive s.c. application at a dose of 162mg every week. |
| Rituximab | Experimental | Drug: MabtheraRituximab (Mabthera®) will be given as 1000mg at weeks 0 and 2, and then repeated at weeks 24 and 26. Patients will receive 100 mg methylprednisolon i.v. before each infusion, as well as 1000mg paracetamol, as well as 50mg diphenhydramine hydrochloride (Dibondrin©). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Men and women, ≥18 and ≤75 years of age, capable of understanding and signing an informed consent.
- Classifiable RA according to the 2010 ACR/EULAR criteria (American College of Rheumatology/European League Against Rheumatism classification criteria) or 1987 ARA criteria (Criteria of American Rheumatology Association) (present or past) (2;3)
- Duration of RA ≤3 years
- Ongoing conventional DMARD therapy (Disease Modifying Antirheumatic Drugs) with methotrexate (at least 20mg/week, or lower if not tolerated in higher doses) or leflunomide (≥100mg/week), for ≥6 months or ≥3 months with documented worsening of disease activity.
- Clinical Disease Activity Index (CDAI)≥15 corresponding to moderate to severe disease activity.
Key exclusion criteria (26 listed)
- Be incapacitated, largely or wholly bedridden, or confined to a wheelchair, or have little or no ability for self care.
- Weigh more than 100 kg
- Use glucocorticoids >10 mg/day prednisone or equivalent
- Have previously received other treatments for their rheumatic disease:
- Have a history of receiving human/murine recombinant products or a known allergy to murine products.
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 |
|---|---|---|
| Remicade- Infliximab (Remicade®) will be administered i.v. at a dose of 3 mg/kg at 0 and 2 weeks, and 5 mg/kg at weeks 6, 14, and 22, 30, 38, and 46. | Drug | Infliximab |
| Orencia- Abatacept (Orencia®) will be given i.v. at weeks 0, 2, 4, and then every 4 weeks until week 48 at a weight adjusted dose: <60 kg Body weight (BW): 500 mg; >60-100 kg BW: 750 mg; alternatively, based on preference and shared decision between patient and physician, patients randomized to the abatacept arm may receive s.c. application at a dose of 125mg weekly. | Drug | Abatacept |
| Ro-Actemra- Tocilizumab (Ro-Actemra®) will be administered every 4 weeks at a dose of 8 mg/kg BW (maximum dose of 800 mg); The employed dosage will be calculated using manufacturer guidelines; alternatively, based on preference and shared decision between patient and physician, patients randomized to the tocilizumab arm may receive s.c. application at a dose of 162mg every week. | Drug | Tocilizumab |
| Mabthera- Rituximab (Mabthera®) will be given as 1000mg at weeks 0 and 2, and then repeated at weeks 24 and 26. Patients will receive 100 mg methylprednisolon i.v. before each infusion, as well as 1000mg paracetamol, as well as 50mg diphenhydramine hydrochloride (Dibondrin©). | Drug | Rituximab |
Primary outcome
Absolute Change in the Simplified Disease Activity Index (SDAI)
Time frame: 24 Weeks
13 secondary outcomes
Relative Change in the SDAI in percent
Time frame: 24 Weeks
Absolute and relative change in the Clinical Disease Activity Index (CDAI) in percent
Time frame: 24 Weeks
Absolute and relative change in the Disease Activity Score 28 (DAS28) in percent
Time frame: 24 weeks
Achieving an SDAI or CDAI response (50%, 70%, 85%)
Time frame: 24 Weeks
Achieving a EULAR response (European League Against Rheumatism)
Time frame: 24 Weeks
Achieving an ACR response (20%, 50%, 70%) (American College of Rheumatology)
Time frame: 24 Weeks
Change in quality of life (EuroQoL-5D, SF-36)
Time frame: 24 weeks
Change in fatigue (Fatigue Score on the Visual Analog Scale)
Time frame: 24 Weeks
Proportion achieving a low disease activity state (SDAI ≤11)
Time frame: 24 Weeks
Proportion achieving a remission state (SDAI ≤3.3)
Time frame: 24 Weeks
Radiographic progression - (Van der Heijde/Sharp Score)
Time frame: 6 months and 12 months
Change in physical function (HAQ)
Time frame: 24 Weeks
Change in sleep (Sleep Score on the Visual Analog Scale)
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 31 Oct 2018.
- Derived from this study: PubMed 34792562Studenic P, Bond G, Kerschbaumer A, Becede M, Pavelka K, Karateev D, Stieger J, Puchner R, Mueller RB, Puchhammer-Stockl E, Durechova M, Loiskandl M, Perkmann T, Olejarova M, Luchikhina E, Steiner CW, Bonelli M, Smolen JS, Aletaha D. Torque Teno Virus quantification for monitoring of immunomodulation with biologic compounds in the treatment of rheumatoid arthritis. Rheumatology (Oxford). 2022 Jul 6;61(7):2815-2825. doi: 10.1093/rheumatology/keab839.
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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.
Daniel Aletaha, MD study director
Medical University of Vienna
9 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Remicade, Orencia and Ro-Actemra in people with Rheumatoid Arthritis, run by Medical University of Vienna at 9 sites in 4 countries.
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 5 inclusion and 26 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 31 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Austria, Czechia, Russia, 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Absolute Change in the Simplified Disease Activity Index (SDAI) (time frame: 24 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01638715, which also lists 1 linked publication.
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 31 Oct 2018.