A Phase 4 interventional study of tocilizumab and methotrexate in Rheumatoid Arthritis, sponsored by Genentech, Inc.. Completed at 47 sites in United States. Open to participants aged 18 Years to 64 Years. Per ClinicalTrials.gov, last updated 2012-12-07.
Sponsored by Genentech, Inc. · Phase 4, Interventional, and Treatment
This randomized, parallel-group, open-label study will evaluate the effect of Actemra (tocilizumab) on vaccination in patients with active rheumatoid arthritis who have an inadequate response to methotrexate and who have had an inadequate clinical response or were intolerant to treatment with one or more anti-tumor necrosis factor (anti-TNF) therapies.
3,554 studies on the registry are indexed under Arthritis; 317 are open to participants now.
This study's enrollment of 91 is close to the median of 90 across 2,377 interventional studies indexed under Arthritis.
Browse Arthritis studies →Genentech, Inc. is the lead sponsor of 507 studies on the registry; 23 are open to participants now.
Of its 90 completed or terminated interventional studies of FDA-regulated products, 50 (56%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants continued to receive their standard dose of methotrexate up to Week 8. From Week 8 participants also received 8 mg/kg tocilizumab intravenously every 4 weeks until Week 20. At Week 3 participants received both pneumococcal and tetanus toxoid vaccinations.
Biological: tocilizumab · Drug: methotrexate · Biological: 23-Valent Pneumococcal Polysaccharide Vaccine · Biological: Tetanus Toxoid Adsorbed Vaccine
Participants received 8 mg/kg tocilizumab intravenously at Baseline (Day 1) and every 4 weeks up to Week 20, in addition to their standard dose of methotrexate. At Week 3 participants received both pneumococcal and tetanus toxoid vaccinations.
Biological: tocilizumab · Drug: methotrexate · Biological: 23-Valent Pneumococcal Polysaccharide Vaccine · Biological: Tetanus Toxoid Adsorbed Vaccine
Intravenous repeating dose
Also known as: RoActemra, Actemra
A stable dose of between 7.5 and 25 mg/week, oral or parenteral.
Intramuscular or subcutaneous injection
Also known as: Pneumovax
Intramuscular injection
Percentage of Participants Who Responded to ≥ 6 of 12 Anti-pneumococcal Antibody Serotypes
Serum levels of antibody to pneumococcal vaccine were drawn 5 weeks after vaccination with 23-valent pneumococcal polysaccharide vaccine to assess humoral immune response. A positive response to the pneumococcal vaccine was defined as a 2-fold increase in serum antibody titers from Baseline or an increase of \> 1 mg/L from Baseline levels. The 12 serotypes evaluated were pneumococcal serotypes 1, 3, 4, 6B, 8, 9N, 12F, 14, 19F, 23F, 7F, and 18C.
Time frame: Baseline (Week 3) and Week 8 (5 weeks post-vaccination)
Percentage of Participants Who Responded to Combinations of 12 Anti-Pneumococcal Antibody Serotypes
Serum levels of antibody to pneumococcal vaccine were drawn 5 weeks after vaccination with 23-valent pneumococcal polysaccharide vaccine to assess humoral immune response. A positive response to the pneumococcal vaccine was defined as a 2-fold increase in serum antibody titers from Baseline or an increase of \> 1 mg/L from Baseline levels. The 12 serotypes evaluated were pneumococcal serotypes 1, 3, 4, 6B, 8, 9N, 12F, 14, 19F, 23F, 7F, and 18C.
Time frame: Baseline (Week 3) and Week 8 (5 weeks post-vaccination)
Percentage of Participants With a Positive Response to Tetanus Toxoid Vaccination
A positive response to the tetanus toxoid vaccination was defined as antibody levels ≥ 0.2 IU/mL for participants with Baseline tetanus antibody levels \< 0.1 IU/mL, or a 4-fold increase in antibody levels compared with Baseline for participants with Baseline tetanus antibody levels ≥ 0.1 IU/mL.
Time frame: Baseline (Week 3) and Week 8 (5 weeks post-vaccination)
Change From Baseline in Levels of Anti-pneumococcal Antibody 5 Weeks After Vaccination
Levels of anti-pneumococcal antibodies were measured by a central laboratory from serum samples taken prior to vaccination (Week 3) and 5 weeks post vaccination (Week 8).
Time frame: Baseline (Week 3) and Week 8 (5 weeks post-vaccination)
Change From Baseline in Levels of Anti-tetanus Antibody 5 Weeks After Vaccination
Levels of anti-tetanus antibodies were measured by a central laboratory from serum samples taken prior to vaccination (Week 3) and 5 weeks post vaccination (Week 8).
Time frame: Baseline (Week 3) and Week 8 (5 weeks post-vaccination)
Percentage of Participants Who Responded to Each of the 12 Anti-Pneumococcal Antibody Serotypes
Serum levels of antibody to pneumococcal vaccine were drawn 5 weeks after vaccination with 23-valent pneumococcal polysaccharide vaccine to assess humoral immune response. A positive response to the pneumococcal vaccine was defined as a 2-fold increase in serum antibody titers from Baseline or an increase of \> 1 mg/L from Baseline levels. The 12 serotypes evaluated were pneumococcal serotypes 1, 3, 4, 6B, 7F, 8, 9N, 12F, 14, 18C, 19F and 23F.
Time frame: Baseline (Week 3) and Week 8 (5 weeks post-vaccination)
Number of Participants With Adverse Events Through Week 8
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A Serious Adverse Event (SAE) is any AE that is fatal or is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is medically significant or requires intervention to prevent one or other of the outcomes listed above.
Time frame: 8 weeks
| Milestone | Methotrexate | Tocilizumab + Methotrexate |
|---|---|---|
| Started | 31 | 60 |
| Per protocol population | 27 | 54 |
| Completed | 25 | 49 |
| Not completed | 6 | 11 |
| Withdrew: Adverse event | 0 | 5 |
| Withdrew: Insufficient therapeutic response | 0 | 1 |
| Withdrew: Protocol violation | 0 | 1 |
| Withdrew: Refused treatment | 6 | 4 |
Serum levels of antibody to pneumococcal vaccine were drawn 5 weeks after vaccination with 23-valent pneumococcal polysaccharide vaccine to assess humoral immune response. A positive response to the pneumococcal vaccine was defined as a 2-fold increase in serum antibody titers from Baseline or an increase of \> 1 mg/L from Baseline levels. The 12 serotypes evaluated were pneumococcal serotypes 1, 3, 4, 6B, 8, 9N, 12F, 14, 19F, 23F, 7F, and 18C.
| percentage of participants | Methotrexate | Tocilizumab + Methotrexate |
|---|---|---|
| Percentage of Participants Who Responded to ≥ 6 of 12 Anti-pneumococcal Antibody Serotypes | 70.8 (52.6 to 89.0) | 60.0 (46.4 to 73.6) |
Serum levels of antibody to pneumococcal vaccine were drawn 5 weeks after vaccination with 23-valent pneumococcal polysaccharide vaccine to assess humoral immune response. A positive response to the pneumococcal vaccine was defined as a 2-fold increase in serum antibody titers from Baseline or an increase of \> 1 mg/L from Baseline levels. The 12 serotypes evaluated were pneumococcal serotypes 1, 3, 4, 6B, 8, 9N, 12F, 14, 19F, 23F, 7F, and 18C.
| percentage of participants | Methotrexate | Tocilizumab + Methotrexate |
|---|---|---|
| Responded to ≥1 out of 12 serotypes | 87.5 (74.3 to 100.0) | 90.0 (81.7 to 98.3) |
| Responded to ≥2 out of 12 serotypes | 87.5 (74.3 to 100.0) | 86.0 (76.4 to 95.6) |
| Responded to ≥3 out of 12 serotypes | 83.3 (68.4 to 98.2) | 80.0 (68.9 to 91.1) |
| Responded to ≥4 out of 12 serotypes | 83.3 (68.4 to 98.2) | 74.0 (61.8 to 86.2) |
| Responded to ≥5 out of 12 serotypes | 83.3 (68.4 to 98.2) | 66.0 (52.9 to 79.1) |
| Responded to ≥6 out of 12 serotypes | 70.8 (52.6 to 89.0) | 60.0 (46.4 to 73.6) |
| Responded to ≥7 out of 12 serotypes | 58.3 (38.6 to 78.1) | 54.0 (40.2 to 67.8) |
| Responded to ≥8 out of 12 serotypes | 58.3 (38.6 to 78.1) | 38.0 (24.5 to 51.5) |
| Responded to ≥9 out of 12 serotypes | 45.8 (25.9 to 65.8) | 32.0 (19.1 to 44.9) |
| Responded to ≥10 out of 12 serotypes | 29.2 (11.0 to 47.4) | 20.0 (8.9 to 31.1) |
| Responded to ≥ 11 out of 12 serotypes | 20.8 (4.6 to 37.1) | 12.0 (3.0 to 21.0) |
| Responded to 12 out of 12 serotypes | 8.3 (0.0 to 19.4) | 6.0 (0.0 to 12.6) |
A positive response to the tetanus toxoid vaccination was defined as antibody levels ≥ 0.2 IU/mL for participants with Baseline tetanus antibody levels \< 0.1 IU/mL, or a 4-fold increase in antibody levels compared with Baseline for participants with Baseline tetanus antibody levels ≥ 0.1 IU/mL.
| percentage of participants | Methotrexate | Tocilizumab + Methotrexate |
|---|---|---|
| Percentage of Participants With a Positive Response to Tetanus Toxoid Vaccination | 39.1 (19.2 to 59.1) | 42.0 (28.3 to 55.7) |
Levels of anti-pneumococcal antibodies were measured by a central laboratory from serum samples taken prior to vaccination (Week 3) and 5 weeks post vaccination (Week 8).
| mg/L | Methotrexate | Tocilizumab + Methotrexate |
|---|---|---|
| Baseline | 91.1 ± 122.91 | 73.9 ± 63.50 |
| Week 8 | 307.2 ± 270.25 | 184.2 ± 197.99 |
| Change from Baseline | 216.1 ± 261.85 | 110.2 ± 188.74 |
Levels of anti-tetanus antibodies were measured by a central laboratory from serum samples taken prior to vaccination (Week 3) and 5 weeks post vaccination (Week 8).
| IU/mL | Methotrexate | Tocilizumab + Methotrexate |
|---|---|---|
| Baseline | 2 ± 1.3 | 2 ± 1.9 |
| Week 8 | 9 ± 12.4 | 9 ± 9.2 |
| Change from Baseline | 7 ± 12.3 | 7 ± 9.0 |
Serum levels of antibody to pneumococcal vaccine were drawn 5 weeks after vaccination with 23-valent pneumococcal polysaccharide vaccine to assess humoral immune response. A positive response to the pneumococcal vaccine was defined as a 2-fold increase in serum antibody titers from Baseline or an increase of \> 1 mg/L from Baseline levels. The 12 serotypes evaluated were pneumococcal serotypes 1, 3, 4, 6B, 7F, 8, 9N, 12F, 14, 18C, 19F and 23F.
| percentage of participants | Methotrexate | Tocilizumab + Methotrexate |
|---|---|---|
| Serotype 1 response [N=24, 49] | 79.2 | 65.3 |
| Serotype 3 response [N=24, 49] | 62.5 | 53.1 |
| Serotype 4 response [N=24, 50] | 33.3 | 38.0 |
| Serotype 6B response [N=24, 50] | 58.3 | 46.0 |
| Serotype 7F response [N=24, 49] | 66.7 | 61.2 |
| Serotype 8 response [N=24, 49] | 75.0 | 59.2 |
| Serotype 9N response [N=23, 50] | 73.9 | 56.0 |
| Serotype 12F response [N=23, 49] | 21.7 | 26.5 |
| Serotype 14 response [N=21, 50] | 57.1 | 56.0 |
| Serotype 18C response [N=24, 50] | 79.2 | 64.0 |
| Serotype 19F response [N=24, 50] | 70.8 | 54.0 |
| Serotype 23F response [N=24, 50] | 50.0 | 44.0 |
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A Serious Adverse Event (SAE) is any AE that is fatal or is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is medically significant or requires intervention to prevent one or other of the outcomes listed above.
| participants | Methotrexate | Tocilizumab + Methotrexate |
|---|---|---|
| Any adverse event | 3 | 23 |
| Serious adverse event | 1 | 2 |
| Deaths | 0 | 0 |
| Withdrawals due to adverse events | 0 | 1 |
Collected over From Day 1 through Week 28.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Methotrexate | — | 1/31 (3.2%) | 9/31 (29%) |
| Tocilizumab + Methotrexate | — | 3/60 (5%) | 25/60 (41.7%) |
| Event | Methotrexate | Tocilizumab + Methotrexate |
|---|---|---|
| CellulitisInfections and infestations | 1/31 | 1/60 |
| Intraspinal abscessInfections and infestations | 0/31 | 1/60 |
| Staphylococcal sepsisInfections and infestations | 0/31 | 1/60 |
| DehydrationMetabolism and nutrition disorders | 0/31 | 1/60 |
| Hypertensive crisisVascular disorders | 0/31 | 1/60 |
| Event | Methotrexate | Tocilizumab + Methotrexate |
|---|---|---|
| Upper respiratory tract infectionInfections and infestations | 3/31 | 4/60 |
| SinusitisInfections and infestations | 1/31 | 5/60 |
| NauseaGastrointestinal disorders | 1/31 | 4/60 |
| HeadacheNervous system disorders | 0/31 | 4/60 |
| NasopharyngitisInfections and infestations | 2/31 | 3/60 |
| Urinary tract infectionInfections and infestations | 2/31 | 2/60 |
| BronchitisInfections and infestations | 0/31 | 3/60 |
| AnxietyPsychiatric disorders | 0/31 | 3/60 |
| RashSkin and subcutaneous tissue disorders | 0/31 | 3/60 |
| Age Continuous(years) | Methotrexate | Tocilizumab + Methotrexate | Total |
|---|---|---|---|
| Mean | 51.4 ± 9.47 | 51.1 ± 8.90 | 51.2 ± 9.04 |
| Sex: Female, Male(Participants) | Methotrexate | Tocilizumab + Methotrexate | Total |
|---|---|---|---|
| Female | 22 | 41 | 63 |
| Male | 5 | 13 | 18 |
| Region of Enrollment(participants) | Methotrexate | Tocilizumab + Methotrexate | Total |
|---|---|---|---|
| United States | 27 | 54 | 81 |
This study is completed, as verified in Nov 2012. You cannot join it, but the record below documents what was studied.
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Genentech, Inc.