An Extension Study of Tocilizumab (Myeloma Receptor Antibody [MRA]) in Patients Completing Treatment in Tocilizumab Core Studies

Rheumatoid Arthritis Clinical Trial

Official title:

Long-term Extension Study of Safety During Treatment With Tocilizumab (MRA) in Patients Completing Treatment in MRA Core Studies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00720798
• Other study ID #: WA18696
• Status: Completed
• Phase: Phase 3
• First received: July 22, 2008
• Last updated: September 26, 2014
• Start date: September 2005
• Est. completion date: April 2013

Study information

• Verified date: September 2014
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This single-arm study evaluated the long-term efficacy and safety of tocilizumab in participants who had completed treatment in the tocilizumab core studies (NCT00106522 [Roche protocol WA18062], NCT00106574 [Roche protocol WA18063], and NCT00109408 [Roche protocol WA17824]) of adults with rheumatoid arthritis. Participants received tocilizumab alone or in combination with standard anti-rheumatic treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2067
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients who have completed participation in 1 of the core studies in adult rheumatoid arthritis.

Exclusion Criteria:

• Treatment with any investigational agent since the last administration of study drug in the core studies.

• Treatment with iv gamma globulin, plasmapheresis, or prosorba column since the last administration of study drug in the core studies.

• Treatment with an anti-TNF or anti-IL1 agent, a T-cell co-stimulation modulator, or any biologic since the last administration of study drug in the core studies.

• Immunization with a live/attenuated vaccine since the last administration of study drug in the core studies.

• Previous treatment with any cell-depleting therapies, including investigational agents.

• Parenteral, intramuscular, or intra-articular corticosteroids within 6 weeks prior to baseline in this study.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Tocilizumab
For participants weighing > 100 kg, the maximum dose of tocilizumab was 800 mg. Tocilizumab was supplied as a sterile solution in vials.
• Disease-modifying anti-rheumatic drugs
Disease-modifying anti-rheumatic drugs included methotrexate, chloroquine, hydroxychloroquine, parenteral gold, sulfasalazine, azathioprine, and leflunomide. These drugs could be used alone or in combination, except for the combination of methotrexate and leflunomide, which was not allowed.
• Non-steroidal anti-inflammatory drugs
Participants could be treated with non-steroidal anti-inflammatory drugs up to the maximum recommended dose throughout the study. The choice and doses of non-steroidal anti-inflammatory drugs were at the discretion of the investigator.
• Oral corticosteroids
Oral corticosteroids (= 10 mg/day) were permitted during the study.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Costa Rica,  Czech Republic,  Denmark,  Finland,  France,  Germany,  Hong Kong,  Iceland,  Israel,  Italy,  Lithuania,  Mexico,  Netherlands,  Norway,  Panama,  Peru,  Portugal,  Puerto Rico,  Russian Federation,  Serbia,  Slovenia,  South Africa,  Spain,  Sweden,  Switzerland,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With = 1 Adverse Event		Baseline to the end of the study (up to 7 years, 7 months)	Yes
Secondary	Percentage of Participants Who Withdrew From Treatment		Baseline to the end of the study (up to 7 years, 7 months)	No
Secondary	Percentage of Participants With Concomitant Oral Corticosteroid Therapy	Concomitant therapy with oral corticosteroids (up 5 to 10 mg daily prednisone or equivalent) was permitted in the study. Reduction of oral corticosteroids was permitted, but not required, if a patient achieved at least a 50% improvement from baseline in both tender joint count and swollen joint count.; The data are reported for each 6-month period of the study where a month = 28 days. The last 6-month period is for months 96 through 101. The actually study duration in 28-day months was 98.85 months.	Baseline to the end of the study (up to 7 years, 7 months)	No
Secondary	Percentage of Participants Who Changed From Monotherapy to Combination Therapy	Participants who entered this study from study WA17824 on tocilizumab monotherapy, who did not achieve a 50% reduction in tender and swollen joint counts from Baseline of study WA17824, could add methotrexate or another allowable disease-modifying anti-rheumatic drug, according to the investigator's practice and as tolerated by the patient, at any time during this study.	Baseline to Week 296	No
Secondary	Percentage of Participants With an Improvement of at Least 20%, 50%, 70%, or 90% in the American College of Rheumatology (ACR) Score (ACR20/50/70/90) From Baseline at Weeks 24, 48, 108, 156, 204, and 264	Improvement must be seen in tender (68 assessed joints) and swollen joint counts (66 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the left end of the scale "no disease activity" [symptom-free and no arthritis symptoms], right end of the scale "maximum disease activity"); patient assessment of pain in the previous 24 hours on a VAS (left end of the scale "no pain", right end of the scale "unbearable pain"); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and erythrocyte sedimentation rate.	Baseline to Week 264	No
Secondary	Percentage of Participants Who Achieved a Major Clinical Response at Weeks 48, 96, 144, 192, and 264	A major clinical response was defined as maintenance of an improvement of at least 70% in the American College of Rheumatology (ACR) score (ACR70) for at least 24 weeks. Improvement must be seen in tender (68 assessed joints) and swollen joint counts (66 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the left end of the scale "no disease activity" [symptom-free and no arthritis symptoms], right end of the scale "maximum disease activity"); patient assessment of pain in the previous 24 hours on a VAS (left end of the scale "no pain", right end of the scale "unbearable pain"); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and erythrocyte sedimentation rate.	Baseline to Week 264	No
Secondary	Percentage of Participants Who Maintained an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) Consecutively for 24, 48, 96, and 264 Weeks at Weeks 48, 96, 144, 192, and 264	Improvement must be seen in tender (68 assessed joints) and swollen joint counts (66 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the left end of the scale "no disease activity" [symptom-free and no arthritis symptoms], right end of the scale "maximum disease activity"); patient assessment of pain in the previous 24 hours on a VAS (left end of the scale "no pain", right end of the scale "unbearable pain"); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and erythrocyte sedimentation rate.	Baseline to Week 264	No
Secondary	Swollen and Tender Joint Count (SJC/TJC) at Baseline and Weeks 24, 48, 108, 156, 204, and 264	The number of swollen (66 assessed joints) and tender (68 assessed joints) joints was assessed. Joints were physically examined and classified as swollen/not swollen and tender/not tender by pressure and joint manipulation.	Baseline to Week 264	No
Secondary	Disease Activity and Pain at Baseline and Weeks 24, 48, 108, 156, 204, and 264	Participant's made a global assessment of their current disease activity on a 100 mm horizontal visual analogue scale (VAS). The left end of the scale indicated "no disease activity" (symptom-free and no arthritis symptoms, score = 0) and the right end indicated "maximum disease activity" (maximum arthritis disease activity, score = 100). The participant's treating physician made a global assessment of the participant's current disease activity on a 100 mm horizontal VAS. The left end of the scale indicated "no disease activity" (symptom-free and no arthritis symptoms, score = 0) and the right end indicated "maximum disease activity" (maximum arthritis disease activity, score = 100). Participant's made an assessment of their current level of pain on a 100 mm horizontal VAS. The left end of the scale indicated "no pain" (score = 0) and the right end of the scale indicated "unbearable pain" (score = 100).	Baseline to Week 264	No
Secondary	Health Assessment Questionnaire-Disability Index Score at Baseline and Weeks 24, 48, 108, 156, 204, and 264	The Health Assessment Questionnaire-Disability Index (HAQ-DI), as a measure of functional ability, consists of 30 questions in 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 4 possible responses to each question (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do). A domain score is the highest score in that domain. To calculate the overall score, the patient must have a domain score in at least 6 of the 8 domains. The HAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score and ranges from 0 (best) to 3 (worst). A higher score indicates less ability.	Baseline to Week 264	No
Secondary	Erythrocyte Sedimentation Rate at Baseline and Weeks 24, 48, 108, 156, 204, and 264	Erythrocyte sedimentation rate (ESR) was determined locally.	Baseline to Week 264	No
Secondary	Change in the Disease Activity Score 28 (DAS-28) From Baseline to Weeks 24, 48, 96, and 264	The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × v(TJC28)) + (0.28 × v(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement.	Baseline to Week 264	No
Secondary	Percentage of Participants Who Were Disease Activity Score 28 (DAS-28) Responders at Weeks 24, 48, 108, 156, 204, and 264	A DAS-28 responder was defined as someone who met the European League Against Rheumatism [EULAR] criteria of a good or moderate response. A change of the DAS-28 score from Baseline was used to determine EULAR responses of good, moderate, or no response. For a post-baseline score = 3.2, a change from baseline of < -1.2 was a good response, < -0.6 to = -1.2 was a moderate response, and = -0.6 was no response. For a post-baseline score > 3.2 to = 5.1, a change from baseline of < -0.6 was a moderate response and = -0.6 was no response. For a post-baseline score > 5.1, a change from baseline < -1.2 was a moderate response and = -1.2 was no response. A good response could not be achieved for post-baseline scores > 3.2.	Baseline to Week 264	No
Secondary	Percentage of Participants Who Maintained a Disease Activity Score 28 (DAS-28) Response for 24, 48, 96, 144, and 192 Weeks at Weeks 48, 96, 144, 192, and 264	A DAS-28 responder was defined as someone who met the European League Against Rheumatism [EULAR] criteria of a good or moderate response. A change of the DAS-28 score from Baseline was used to determine EULAR responses of good, moderate, or no response. For a post-baseline score = 3.2, a change from baseline of < -1.2 was a good response, < -0.6 to = -1.2 was a moderate response, and = -0.6 was no response. For a post-baseline score > 3.2 to = 5.1, a change from baseline of < -0.6 was a moderate response and = -0.6 was no response. For a post-baseline score > 5.1, a change from baseline < -1.2 was a moderate response and = -1.2 was no response. A good response could not be achieved for post-baseline scores > 3.2.	Baseline to Week 264	No
Secondary	Percentage of Participants With a Clinically Relevant Improvement in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Weeks 24, 36, 48, 108, 156, 204, and 264	The FACIT-F is a 13-item participant self-report questionnaire that assesses fatigue over the previous 7 days by scoring each item on a 5-point scale (0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit, 4=Very much). An overall FACIT-F score was obtained by summing the scores of all 13 items. The overall score ranged from 0 to 52. A lower score indicates less fatigue. A clinically relevant improvement in the FACIT-F score was defined as a = 5-point increase from Baseline.	Baseline to Week 264	No
Secondary	Percentage of Participants With a Clinically Relevant Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Weeks 24, 48, 108, 156, 204, and 264	The SF-36 Health Survey uses participant-reported symptoms on 8 subscales to assess health-related quality of life (HRQoL). The Physical Component Summary (PCS) score summarizes the subscales Physical Functioning, Role-Physical, Bodily Pain, and General Health. The Mental Component Summary (MCS) score summarizes the subscales Vitality, Social Functioning, Role-Emotional, and Mental Health. Each score was scaled from 0 to 100 with a higher score indicating better HRQoL. A clinically relevant improvement in the Physical and Mental Component Scores of the SF-36 was defined as a = 5-point increase from Baseline.	Baseline to Week 264	No