Rheumatoid ArthritisPhase 3SERENENCT00299130
A Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate Compared to Methotrexate Alone in Patients With Active Rheumatoid Arthritis
A Phase 3 study testing Folate, Methotrexate and Methylprednisolone in people with Rheumatoid Arthritis, run by Genentech, Inc..
Trial summary
This study evaluated the efficacy and safety of rituximab in patients with active rheumatoid arthritis (RA). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Folate, Methotrexate and Methylprednisolone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 511 participants
- Where
- No sites listed yet
- Study dates
- Oct 2005to Jul 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients 18-80 years of age.
- Rheumatoid arthritis (RA) for ≥ 6 months, diagnosed according to the revised 1987 American College of Rheumatology (ACR) criteria for the classification of rheumatoid arthritis.
- Receiving outpatient treatment for RA.
- Swollen joint count (SJC) ≥ 8 (66 joint count), and tender joint count (TJC) ≥ 8 (68 joint count) at screening and baseline.
- At screening, either
- C-reactive protein (CRP) ≥ 0.6 mg/dL (6 mg/L), or
- Erythrocyte sedimentation rate (ESR) ≥ 28 mm/hour.
- Inadequate response to methotrexate, having received and tolerated at a dose of 10-25 mg/week it for ≥ 12 weeks.
Who cannot join
- Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA.
- Inflammatory joint disease other than RA, or other systemic autoimmune disorder.
- Diagnosis of juvenile rheumatoid arthritis, or RA before the age of 16.
- Surgery within 12 weeks of study or planned within 24 weeks of randomization.
- Previous treatment with any approved or investigational biological agent for RA, an anti-alpha4-integrin antibody or co-stimulation modulator, or cell-depleting therapy.
About this study
Official title: A Randomized, Placebo Controlled, Double-blind, Parallel Group, International Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate, Compared to Methotrexate Monotherapy, in Patients With Active Rheumatoid Arthritis
This study evaluated the efficacy and safety of rituximab in patients with active rheumatoid arthritis (RA).
- Conditions
- Rheumatoid Arthritis
- Being tested
- Folate, Methotrexate, Methylprednisolone, Placebo, Rituximab
- Keywords
- RA, Rituxan, SERENE
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FolateDrug
A stable dose, ≥ 5 mg/week given as either a single dose or as a divided weekly dose, orally.
MethotrexateDrug
A stable dose of between 10-25 mg/week, oral or parenteral, as prescribed by the treating physician.
Intravenous infusion
PlaceboDrug
Placebo to rituximab intravenous infusion
RituximabDrug
Also called MabThera®, Rituxan®
Intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Placebo + methotrexate (MTX) | Active comparator | Participants received placebo intravenous infusion on Days 1 and 15. From Week 16 onwards, participants could switch to receive rituximab 0.5 g (on Days 1 and 15) every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Placebo and rituximab infusions were preceded with 100 milligrams (mg) intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of MTX and ≥ 5 mg/week folic acid for the duration of their participation in the study.
All participants entered a 48-week safety follow-up (SFU) period following the treatment period. Receives: Drug: Folate; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Placebo; Drug: Rituximab |
| Rituximab 2 x 0.5 g + MTX | Experimental | Participants received 0.5 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone.
Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study.
All participants entered a 48-week safety follow-up (SFU) period following the treatment period. Receives: Drug: Folate; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Rituximab |
| Rituximab 2 x 1.0 g + MTX | Experimental | Participants received 1.0 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone.
Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study.
All participants entered a 48-week safety follow-up (SFU) period following the treatment period. Receives: Drug: Folate; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24
To achieve an ACR20 required at least a 20% improvement compared with Baseline in both tender joint counts (68 joints assessed for tenderness) and swollen joint counts (66 joints assessed for swelling), as well as a 20% improvement in three of the following five additional measurements:
- Physician's global assessment of disease activity (assessed using a 100 mm Visual Analog Scale [VAS]);
- Patient's global assessment of disease activity (assessed using a 100 mm VAS);
- Patient's assessment of pain (assessed using a 100 mm VAS);
- Health Assessment Questionnaire (HAQ; a patient completed questionnaire consisting of 20 questions, scored from 0-3);
- Acute phase reactant: C-reactive protein (CRP) or, if CRP was missing, erythrocyte sedimentation rate (ESR).
Participants who withdrew prematurely from the study prior to Week 24, who received rescue therapy or had insufficient data in order to calculate a clinical response were considered to be non-responders.
Measured: Baseline and Week 24
Secondary outcomes (29)
Percentage of Participants With an ACR50 Response at Week 24
To achieve an ACR50 required at least a 50% improvement compared with Baseline in both tender joint counts (68 joints assessed for tenderness) and swollen joint counts (66 joints assessed for swelling), as well as a 50% improvement in three of the following five additional measurements:
- Physician's global assessment of disease activity (assessed using a 100 mm Visual Analog Scale [VAS]);
- Patient's global assessment of disease activity (assessed using a 100 mm VAS);
- Patient's assessment of pain (assessed using a 100 mm VAS);
- Health Assessment Questionnaire (HAQ; a patient completed questionnaire consisting of 20 questions, scored from 0-3);
- Acute phase reactant: C-reactive protein (CRP) or, if CRP was missing, erythrocyte sedimentation rate (ESR).
Participants who withdrew prematurely from the study prior to Week 24, who received rescue therapy or had insufficient data in order to calculate a clinical response were considered to be non-responders.
Measured: Baseline and Week 24
Percentage of Participants With an ACR70 Response at Week 24
To achieve an ACR70 required at least a 70% improvement compared with Baseline in both tender joint counts (68 joints assessed for tenderness) and swollen joint counts (66 joints assessed for swelling), as well as a 70% improvement in three of the following five additional measurements:
- Physician's global assessment of disease activity (assessed using a 100 mm Visual Analog Scale [VAS]);
- Patient's global assessment of disease activity (assessed using a 100 mm VAS);
- Patient's assessment of pain (assessed using a 100 mm VAS);
- Health Assessment Questionnaire (HAQ; a patient completed questionnaire consisting of 20 questions, scored from 0-3);
- Acute phase reactant: C-reactive protein (CRP) or, if CRP was missing, erythrocyte sedimentation rate (ESR).
Participants who withdrew prematurely from the study prior to Week 24, who received rescue therapy or had insufficient data in order to calculate a clinical response were considered to be non-responders.
Measured: Baseline and Week 24
Change From Baseline in Disease Activity Score (DAS28-ESR) at Week 24
The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables:
- The number of swollen and tender joints assessed using the 28-joint count;
- Erythrocyte sedimentation rate (ESR);
- Patient's global assessment of disease activity measured on a 100 mm visual analog scale.
The DAS28 score ranges from zero to ten. A DAS28 score above 5.1 means high disease activity whereas a DAS28 less than or equal to 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6.
Measured: Baseline and Week 24
Percentage of Participants With European League Against Rheumatism (EULAR) Response at Week 24
A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS28 score. The DAS28 score ranges from 0-10, with higher scores indicating more disease activity.
A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score of less than or equal to 3.2.
A Moderate Response is defined as either:
- an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 from Baseline and attainment of a DAS28 score of less than or equal to 5.1 or,
- an improvement (decrease) in the DAS28 of more than 1.2 from Baseline and attainment of a DAS28 score of greater than 3.2.
No Response is defined as either an improvement (decrease) in the DAS28 of less than or equal to 0.6, or an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 of more than 5.1.
Measured: Baseline and Week 24
Percent Change From Baseline in Swollen Joint Count
Sixty-six joints were assessed and classified as swollen/not swollen by pressure and joint manipulation on physical examination.
The percentage change from baseline at each post-baseline visit was calculated as:
[(post-baseline value minus baseline value) divided by Baseline value]*100.
A negative percentage change from baseline score indicates an improvement.
Measured: Baseline, Week 24 and Week 48
Percent Change From Baseline in Tender Joint Count
Sixty-eight joints were assessed and classified as tender/not tender by pressure and joint manipulation on physical examination.
The percentage change from baseline at each post-baseline visit was calculated as:
[(post-baseline value minus baseline value) divided by Baseline value]*100.
A negative percentage change from baseline score indicates an improvement.
Measured: Baseline, Week 24 and Week 48
Percent Change From Baseline in Patient's Global Assessment of Disease Activity
The participant's overall assessment of their current disease activity measured on a 100 mm horizontal visual analog scale (VAS). The left-hand extreme of the line (0 mm) was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme (100 mm) as "maximum disease activity" (maximum arthritis disease activity).
The percentage change from baseline at each post-baseline visit was calculated as:
[(post-baseline value minus baseline value) divided by Baseline value]*100.
A negative percentage change from baseline score indicates an improvement.
Measured: Baseline, Week 24 and Week 48
Percent Change From Baseline in Patient's Pain Assessment
The participant's assessment of their current level of pain on a 100 mm horizontal visual analog scale (VAS), where the left-hand extreme of the line (0 mm) was described as "no pain" and the right-hand extreme (100 mm) as "unbearable pain".
The percentage change from baseline at each post-baseline visit was calculated as:
[(post-baseline value minus baseline value) divided by Baseline value]*100.
A negative percentage change from baseline score indicates an improvement.
Measured: Baseline, Week 24 and Week 48
Percent Change From Baseline in Physician's Global Assessment of Disease Activity
The physician's assessment of the participant's current disease activity on a 100 mm horizontal VAS, where the left-hand extreme of the line (0 mm) was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme (100 mm) as "maximum disease activity".
The percentage change from baseline at each post-baseline visit was calculated as:
[(post-baseline value minus baseline value) divided by Baseline value]*100.
A negative percentage change from baseline score indicates an improvement.
Measured: Baseline, Week 24 and Week 48
Percent Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score
The Stanford Health Assessment Questionnaire disability index is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants choose from four response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where zero represents no disability and three very severe, high-dependency disability.
The percentage change from baseline at each post-baseline visit was calculated as:
[(post-baseline value minus baseline value) divided by Baseline value]*100.
A negative percentage change from baseline score indicates an improvement.
Measured: Baseline, Week 24 and Week 48
Percent Change From Baseline in C-Reactive Protein
C-Reactive Protein (CRP) was measured from blood samples by a central laboratory as a marker for inflammation.
The percentage change from baseline at each post-baseline visit was calculated as:
[(post-baseline value minus baseline value) divided by Baseline value]*100.
A negative percentage change from baseline score indicates an improvement.
Measured: Baseline, Week 24 and Week 48
Percent Change From Baseline in Erythrocyte Sedimentation Rate
Erythrocyte sedimentation rate (ESR) indirectly measures how much inflammation is in the body. A higher ESR is indicative of increased inflammation.
The percentage change from baseline at each post-baseline visit was calculated as:
[(post-baseline value minus baseline value) divided by Baseline value]*100.
A negative percentage change from baseline score indicates an improvement.
Measured: Baseline, Week 24 and Week 48
Percent Change From Baseline in Short Form 36 Health Survey (SF-36) Summary Scores (Physical and Mental Components)
The SF-36 measures the impact of disease on overall quality of life and consists of 36 questions split into two major components: physical health and mental health. Under physical health are the following four domains: physical health, bodily pain, physical functioning and physical role limitations. Under the mental health domain there are four domains; mental health, vitality, social functioning, and emotional role limitation. The individual domain scores are aggregated to derive a physical-component summary score and a mental-component summary score which range from 0 to 100, with higher scores indicating a better level of functioning.
The percentage change from baseline at each post-baseline visit was calculated as:
[(post-baseline value minus baseline value) divided by Baseline value]*100.
A positive percentage change from baseline score indicates an improvement.
Measured: Baseline, Week 24 and Week 48
Change From Baseline in Short Form 36 Health Survey (SF-36) General Health Domain Score
The SF-36 measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning.
A positive change from baseline score indicates an improvement.
Measured: Baseline, Week 24 and Week 48
Change From Baseline in Short Form 36 Health Survey (SF-36) Bodily Pain Domain Score
The SF-36 measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning.
A positive change from baseline score indicates an improvement.
Measured: Baseline, Week 24 and Week 48
Change From Baseline in Short Form 36 Health Survey (SF-36) Physical Functioning Domain Score
The SF-36 measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning.
A positive change from baseline score indicates an improvement.
Measured: Baseline, Week 24 and Week 48
Change From Baseline in Short Form 36 Health Survey (SF-36) Physical Role Limitations Domain Score
The SF-36 measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning.
A positive change from baseline score indicates an improvement.
Measured: Baseline, Week 24 and Week 48
Change From Baseline in Short Form 36 Health Survey (SF-36) Mental Health Domain Score
The SF-36 measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning.
A positive change from baseline score indicates an improvement.
Measured: Baseline, Week 24 and Week 48
Change From Baseline in Short Form 36 Health Survey (SF-36) Vitality Domain Score
The SF-36 measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning.
A positive change from baseline score indicates an improvement.
Measured: Baseline, Week 24 and Week 48
Change From Baseline in Short Form 36 Health Survey (SF-36) Social Functioning Domain Score
The SF-36 measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning.
A positive change from baseline score indicates an improvement.
Measured: Baseline, Week 24 and Week 48
Change From Baseline in Short Form 36 Health Survey (SF-36) Emotional Role Limitations Domain Score
The SF-36 measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning.
A positive change from baseline score indicates an improvement.
Measured: Baseline, Week 24 and Week 48
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Scores
The FACIT-Fatigue questionnaire is a self-administered patient questionnaire that consists of 13 questions designed to measure the degree of fatigue experienced by participants in the previous 7 days. Participants respond to the questions using a value in the range of 0 (not at all) to 4 (very much). The scale score is computed by summing the item scores, after reversing those items that are worded in the negative direction. The FACIT-Fatigue subscale score ranges from 0 to 52, where higher scores represent less fatigue.
A positive change from baseline score indicates an improvement.
Measured: Baseline, Week 24 and Week 48
Percentage of Participants With DAS28-ESR Low Disease Activity Score and Clinical Remission at Week 24
The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables:
- The number of swollen and tender joints assessed using the 28-joint count;
- Erythrocyte sedimentation rate (ESR);
- Patient's global assessment of disease activity measured on a 100 mm visual analog scale.
The DAS28 score ranges from zero to ten. DAS28 above 5.1 indicates high disease activity.
Low disease activity is defined by a DAS28 score less than or equal to 3.2. Remission is defined by a DAS28 score less than 2.6.
Measured: Week 24
Percentage of Participants With HAQ-DI Improved, Unchanged or Worsened at Week 24
The Stanford Health Assessment Questionnaire disability index is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants choose from four response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A negative change from baseline score indicates an improvement.
Improved HAQ-DI is defined as a change from Baseline score less than or equal to -0.22.
An Unchanged HAQ-DI is defined as a change from Baseline score greater than -0.22 and less than 0.22.
A worsened HAQ-DI score is defined as a change from Baseline score of greater than or equal to 0.22.
Measured: Baseline and Week 24
Percentage of Participants With HAQ-DI Improved, Unchanged or Worsened at Week 48
The Stanford Health Assessment Questionnaire disability index is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants choose from four response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A negative change from baseline score indicates an improvement.
Improved HAQ-DI is defined as a change from Baseline score less than or equal to -0.22.
An Unchanged HAQ-DI is defined as a change from Baseline score greater than -0.22 and less than 0.22.
A worsened HAQ-DI score is defined as a change from Baseline score of greater than or equal to 0.22.
Measured: Baseline and Week 48
Percentage of Participants With European League Against Rheumatism (EULAR) Response at Week 48
A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score.
A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2.
A Moderate Response is defined as either:
- an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or,
- an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2.
No Response is defined as either an improvement (decrease) in the DAS28 of less than or equal to 0.6, or an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of 5.1 or higher.
Measured: Baseline and Week 48
Percentage of Participants With DAS28-ESR Low Disease Activity Score and Clinical Remission at Week 48
The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables:
- The number of swollen and tender joints assessed using the 28-joint count;
- Erythrocyte sedimentation rate (ESR);
- Patient's global assessment of disease activity measured on a 100 mm visual analog scale.
The DAS28 score ranges from zero to ten. DAS28 above 5.1 indicates high disease activity.
Low disease activity is defined by a DAS28 score less than or equal to 3.2. Remission is defined by a DAS28 score less than 2.6.
Measured: Week 48
Percentage of Participants With an ACR50 Response at Week 48
To achieve an ACR50 required at least a 50% improvement compared with Baseline in both tender joint counts (68 joints assessed for tenderness) and swollen joint counts (66 joints assessed for swelling), as well as a 50% improvement in three of the following five additional measurements:
- Physician's global assessment of disease activity (assessed using a 100 mm Visual Analog Scale [VAS]);
- Patient's global assessment of disease activity (assessed using a 100 mm VAS);
- Patient's assessment of pain (assessed using a 100 mm VAS);
- Health Assessment Questionnaire (HAQ; a patient completed questionnaire consisting of 20 questions, scored from 0-3);
- Acute phase reactant: C-reactive protein (CRP) or, if CRP was missing, erythrocyte sedimentation rate (ESR).
Participants who withdrew prematurely from the study prior to week 48, who received rescue therapy or had insufficient data in order to calculate a clinical response were considered to be non-responders.
Measured: Baseline and Week 48
Percentage of Participants With an ACR70 Response at Week 48
To achieve an ACR70 required at least a 70% improvement compared with baseline in both tender joint counts (68 joints assessed for tenderness) and swollen joint counts (66 joints assessed for swelling), as well as a 70% improvement in three of the following five additional measurements:
- Physician's global assessment of disease activity (assessed using a 100 mm Visual Analog Scale [VAS]);
- Patient's global assessment of disease activity (assessed using a 100 mm VAS);
- Patient's assessment of pain (assessed using a 100 mm VAS);
- Health Assessment Questionnaire (HAQ; a patient completed questionnaire consisting of 20 questions, scored from 0-3);
- Acute phase reactant: C-reactive protein (CRP) or, if CRP was missing, erythrocyte sedimentation rate (ESR).
Participants who withdrew prematurely from the study prior to Week 48, who received rescue therapy or had insufficient data in order to calculate a clinical response were considered to be non-responders.
Measured: Baseline and Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2006 (estimated)
- Study startOct 2005
- Primary completionJun 2008
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)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 Genentech, Inc.The 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 511 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hoffmann-La Roche
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00299130
- Sponsor's protocol ID
- U2973g
- Other IDs
- WA17045
- Acronym
- SERENE
- Status last verified
- Mar 2017
- First submitted
- 3 Mar 2006
- Last updated
- 17 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Emery P, Deodhar A, Rigby WF, Isaacs JD, Combe B, Racewicz AJ, Latinis K, Abud-Mendoza C, Szczepanski LJ, Roschmann RA, Chen A, Armstrong GK, Douglass W, Tyrrell H. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE)). Ann Rheum Dis. 2010 Sep;69(9):1629-35. doi: 10.1136/ard.2009.119933. Epub 2010 May 20.
PubMed 20488885Lal P, Su Z, Holweg CT, Silverman GJ, Schwartzman S, Kelman A, Read S, Spaniolo G, Monroe JG, Behrens TW, Townsend MJ. Inflammation and autoantibody markers identify rheumatoid arthritis patients with enhanced clinical benefit following rituximab treatment. Arthritis Rheum. 2011 Dec;63(12):3681-91. doi: 10.1002/art.30596.
PubMed 22127691
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo Controlled, Double-blind, Parallel Group, International Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate, Compared to Methotrexate Monotherapy, in Patients With Active Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT00299130
- Acronym / sponsor ID
- SERENE / U2973g
- Conditions
- Rheumatoid Arthritis
- Keywords
- RA, Rituxan, SERENE
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 511 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Hoffmann-La Roche
- Study start
- Oct 2005
- Primary completion
- Jun 2008 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 6 Mar 2006 (estimated)
- Results
- Posted 28 Jun 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluated the efficacy and safety of rituximab in patients with active rheumatoid arthritis (RA).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo + methotrexate (MTX) | Active comparator | Drug: Folate, Drug: Methotrexate, Drug: Methylprednisolone, Drug: Placebo, Drug: RituximabParticipants received placebo intravenous infusion on Days 1 and 15. From Week 16 onwards, participants could switch to receive rituximab 0.5 g (on Days 1 and 15) every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Placebo and rituximab infusions were preceded with 100 milligrams (mg) intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of MTX and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period. |
| Rituximab 2 x 0.5 g + MTX | Experimental | Drug: Folate, Drug: Methotrexate, Drug: Methylprednisolone, Drug: RituximabParticipants received 0.5 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period. |
| Rituximab 2 x 1.0 g + MTX | Experimental | Drug: Folate, Drug: Methotrexate, Drug: Methylprednisolone, Drug: RituximabParticipants received 1.0 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Adult patients 18-80 years of age.
- Rheumatoid arthritis (RA) for ≥ 6 months, diagnosed according to the revised 1987 American College of Rheumatology (ACR) criteria for the classification of rheumatoid arthritis.
- Receiving outpatient treatment for RA.
- Swollen joint count (SJC) ≥ 8 (66 joint count), and tender joint count (TJC) ≥ 8 (68 joint count) at screening and baseline.
- At screening, either
Key exclusion criteria (5 listed)
- Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA.
- Inflammatory joint disease other than RA, or other systemic autoimmune disorder.
- Diagnosis of juvenile rheumatoid arthritis, or RA before the age of 16.
- Surgery within 12 weeks of study or planned within 24 weeks of randomization.
- Previous treatment with any approved or investigational biological agent for RA, an anti-alpha4-integrin antibody or co-stimulation modulator, or cell-depleting therapy.
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 |
|---|---|---|
| FolateA stable dose, ≥ 5 mg/week given as either a single dose or as a divided weekly dose, orally. | Drug | Placebo + methotrexate (MTX), Rituximab 2 x 0.5 g + MTX, Rituximab 2 x 1.0 g + MTX |
| MethotrexateA stable dose of between 10-25 mg/week, oral or parenteral, as prescribed by the treating physician. | Drug | Placebo + methotrexate (MTX), Rituximab 2 x 0.5 g + MTX, Rituximab 2 x 1.0 g + MTX |
| MethylprednisoloneIntravenous infusion | Drug | Placebo + methotrexate (MTX), Rituximab 2 x 0.5 g + MTX, Rituximab 2 x 1.0 g + MTX |
| PlaceboPlacebo to rituximab intravenous infusion | Drug | Placebo + methotrexate (MTX) |
| RituximabAlso: MabThera®, Rituxan®Intravenous infusion | Drug | Placebo + methotrexate (MTX), Rituximab 2 x 0.5 g + MTX, Rituximab 2 x 1.0 g + MTX |
Primary outcome
Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24
Time frame: Baseline and Week 24
To achieve an ACR20 required at least a 20% improvement compared with Baseline in both tender joint counts (68 joints assessed for tenderness) and swollen joint counts (66 joints assessed for swelling), as well as a 20% improvement in three of the following five additional measurements: * Physician's global assessment of disease activity (assessed using a 100 mm Visual Analog Scale [VAS]); * Patient's global assessment of disease activity (assessed using a 100 mm VAS); * Patient's assessment of pain (assessed using a 100 mm VAS); * Health Assessment Questionnaire (HAQ; a patient completed questionnaire consisting of 20 questions, scored from 0-3); * Acute phase reactant: C-reactive protein (CRP) or, if CRP was missing, erythrocyte sedimentation rate (ESR). Participants who withdrew prematurely from the study prior to Week 24, who received rescue therapy or had insufficient data in order to calculate a clinical response were considered to be non-responders.
29 secondary outcomes
Percentage of Participants With an ACR50 Response at Week 24
Time frame: Baseline and Week 24
Percentage of Participants With an ACR70 Response at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Disease Activity Score (DAS28-ESR) at Week 24
Time frame: Baseline and Week 24
Percentage of Participants With European League Against Rheumatism (EULAR) Response at Week 24
Time frame: Baseline and Week 24
Percent Change From Baseline in Swollen Joint Count
Time frame: Baseline, Week 24 and Week 48
Percent Change From Baseline in Tender Joint Count
Time frame: Baseline, Week 24 and Week 48
Percent Change From Baseline in Patient's Global Assessment of Disease Activity
Time frame: Baseline, Week 24 and Week 48
Percent Change From Baseline in Patient's Pain Assessment
Time frame: Baseline, Week 24 and Week 48
Percent Change From Baseline in Physician's Global Assessment of Disease Activity
Time frame: Baseline, Week 24 and Week 48
Percent Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score
Time frame: Baseline, Week 24 and Week 48
Percent Change From Baseline in C-Reactive Protein
Time frame: Baseline, Week 24 and Week 48
Percent Change From Baseline in Erythrocyte Sedimentation Rate
Time frame: Baseline, Week 24 and Week 48
Percent Change From Baseline in Short Form 36 Health Survey (SF-36) Summary Scores (Physical and Mental Components)
Time frame: Baseline, Week 24 and Week 48
Change From Baseline in Short Form 36 Health Survey (SF-36) General Health Domain Score
Time frame: Baseline, Week 24 and Week 48
Change From Baseline in Short Form 36 Health Survey (SF-36) Bodily Pain Domain Score
Time frame: Baseline, Week 24 and Week 48
Change From Baseline in Short Form 36 Health Survey (SF-36) Physical Functioning Domain Score
Time frame: Baseline, Week 24 and Week 48
Change From Baseline in Short Form 36 Health Survey (SF-36) Physical Role Limitations Domain Score
Time frame: Baseline, Week 24 and Week 48
Change From Baseline in Short Form 36 Health Survey (SF-36) Mental Health Domain Score
Time frame: Baseline, Week 24 and Week 48
Change From Baseline in Short Form 36 Health Survey (SF-36) Vitality Domain Score
Time frame: Baseline, Week 24 and Week 48
Change From Baseline in Short Form 36 Health Survey (SF-36) Social Functioning Domain Score
Time frame: Baseline, Week 24 and Week 48
Change From Baseline in Short Form 36 Health Survey (SF-36) Emotional Role Limitations Domain Score
Time frame: Baseline, Week 24 and Week 48
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Scores
Time frame: Baseline, Week 24 and Week 48
Percentage of Participants With DAS28-ESR Low Disease Activity Score and Clinical Remission at Week 24
Time frame: Week 24
Percentage of Participants With HAQ-DI Improved, Unchanged or Worsened at Week 24
Time frame: Baseline and Week 24
Percentage of Participants With HAQ-DI Improved, Unchanged or Worsened at Week 48
Time frame: Baseline and Week 48
Percentage of Participants With European League Against Rheumatism (EULAR) Response at Week 48
Time frame: Baseline and Week 48
Percentage of Participants With DAS28-ESR Low Disease Activity Score and Clinical Remission at Week 48
Time frame: Week 48
Percentage of Participants With an ACR50 Response at Week 48
Time frame: Baseline and Week 48
Percentage of Participants With an ACR70 Response at Week 48
Time frame: Baseline and Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20488885Emery P, Deodhar A, Rigby WF, Isaacs JD, Combe B, Racewicz AJ, Latinis K, Abud-Mendoza C, Szczepanski LJ, Roschmann RA, Chen A, Armstrong GK, Douglass W, Tyrrell H. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE)). Ann Rheum Dis. 2010 Sep;69(9):1629-35. doi: 10.1136/ard.2009.119933. Epub 2010 May 20.
- Derived from this study: PubMed 22127691Lal P, Su Z, Holweg CT, Silverman GJ, Schwartzman S, Kelman A, Read S, Spaniolo G, Monroe JG, Behrens TW, Townsend MJ. Inflammation and autoantibody markers identify rheumatoid arthritis patients with enhanced clinical benefit following rituximab treatment. Arthritis Rheum. 2011 Dec;63(12):3681-91. doi: 10.1002/art.30596.
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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.
Clinical Trials study director
Genentech, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Folate, Methotrexate and Methylprednisolone in people with Rheumatoid Arthritis, run by Genentech, Inc..
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 8 inclusion and 5 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 17 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24 (time frame: Baseline and Week 24). 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 NCT00299130, which also lists 2 linked publications.
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 17 Apr 2017.