Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02518620 | An Open-Label Extension Study Assessing the Long-Term Efficacy and Safety of ALX-0061 in Subjects With Rheumatoid Arthritis | PHASE2 | COMPLETED | 406 | — | — | Jul 1, 2015 | Aug 1, 2018 | Jul 30, 2019 | 57 | Belgium, Bulgaria +10 |
| NCT02287922 | A Phase IIb Study for ALX-0061 Monotherapy in Subjects With Rheumatoid Arthritis | PHASE2 | COMPLETED | 251 | — | — | Mar 1, 2015 | Jul 1, 2016 | Aug 21, 2019 | 83 | United States, Belgium +12 |
| NCT02309359 | A Dose-Range Finding Study for ALX-0061 Combination Therapy in Subjects With Rheumatoid Arthritis | PHASE2 | COMPLETED | 345 | — | — | Jan 1, 2015 | Aug 1, 2016 | Aug 21, 2019 | 94 | United States, Belgium +12 |
| NCT02101073 | ALX-0061 Phase I Bioavailability Study in Healthy Volunteers | PHASE1 | COMPLETED | 70 | — | — | Mar 31, 2014 | Jul 31, 2014 | Jan 4, 2019 | 1 | Netherlands |
| NCT01284569 | Study to Assess Safety and Efficacy of Anti-Interleukin 6-receptor (IL6R) Nanobody in Rheumatoid Arthritis (RA) Patients | PHASE1 | COMPLETED | 65 | — | — | Mar 1, 2011 | Sep 1, 2012 | Jan 4, 2019 | 7 | Czechia, Hungary +1 |
ACR 20 response is defined as: * 20% improvement in tender joint count (TJC; 68 joints) relative to Week 0 AND * 20% improvement in swollen joint count (SJC; 66 joints) relative to Week 0 AND * 20% improvement in 3 of the following 5 areas relative to Week 0: * Subject's Assessment of Pain (100 mm - visual analogue scale \[VAS\]) * Subject's Global Assessment of Disease Activity (VASPA) * Physician's Global Assessment of Disease Activity (VASPHA) * Subject's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) * C-reactive protein (CRP) level ACR20 responses were measured at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, and 104 and Weeks 0, 12, 48, and 104 reported.
ACR50 response is defined as: * 50% improvement in TJC (68 joints) relative to Week 0 AND * 50% improvement in SJC (66 joints) relative to Week 0 AND * 50% improvement in 3 of the following 5 areas relative to Week 0: * Subject's Assessment of Pain (100 mm - VAS) * Subject's Global Assessment of Disease Activity (VASPA) * Physician's Global Assessment of Disease Activity (VASPHA) * Subject's assessment of physical function as measured by HAQ-DI * CRP level ACR50 responses were measured at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, and 104 and Weeks 0, 12, 48, and 104 reported.
ACR70 response is defined as: * 70% improvement in TJC (68 joints) relative to Week 0 AND * 70% improvement in SJC (66 joints) relative to Week 0 AND * 70% improvement in 3 of the following 5 areas relative to Week 0: * Subject's Assessment of Pain (100 mm - VAS) * Subject's Global Assessment of Disease Activity (VASPA) * Physician's Global Assessment of Disease Activity (VASPHA) * Subject's assessment of physical function as measured by HAQ-DI * CRP level ACR70 responses were measured at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, and 104 and Weeks 0, 12, 48, and 104 reported.
The ACR-N Index of Improvement is defined as the minimum of the following 3 criteria: * The percent improvement from Week 0 in TJCs * The percent improvement from Week 0 in SJCs * The median percent improvement from Week 0 for the following 5 assessments: * Subject's assessment of pain (VAS) * Subject's global assessment of disease activity (VASPHA) * Physician's global assessment of disease activity (VASPHA) * Subject's assessment of physical function as measured by the HAQ-DI * CRP level ACR-N Index of Improvement was measured at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, and 104 and Weeks 0, 12, 48, and 104 reported.
DAS28(ESR) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.70 × ln\[ESR\]) +(0.014 × VASPA) * Remission = DAS28(ESR) \< 2.6 * Low disease activity = 2.6 ≤ DAS28 ≤ 3.2 * Moderate disease activity = 3.2 \< DAS28 ≤ 5.1 * High disease activity = DAS28 \> 5.1 Disease activity based on DAS28(ESR) was measured at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, and 104 and Weeks 0, 12, 48, and 104 reported.
DAS28(CRP) = (0.56 × √TJC28) + (0.28 × √SJC28) + (0.36 × ln\[CRP+1\]) + (0.014 × VASPA) + 0.96 * DAS28(CRP) \< 2.6 * Low disease activity = 2.6 ≤ DAS28 ≤ 3.2 * Moderate disease activity = 3.2 \< DAS28 ≤ 5.1 * High disease activity = DAS28 \> 5.1 Disease activity based on DAS28(CRP) was measured at Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, and 104 and Weeks 0, 12, 48, and 104 reported.
ACR 20 response is defined as: * 20% improvement in tender joint count (TJC; 68 joints) relative to Week 0 AND * 20% improvement in swollen joint count (SJC; 66 joints) relative to Week 0 AND * 20% improvement in 3 of the following 5 areas relative to Week 0: * Subject's Assessment of Pain (100 mm - visual analogue scale \[VAS\]) * Subject's Global Assessment of Disease Activity (VASPA) * Physician's Global Assessment of Disease Activity (VASPHA) * Subject's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) * C-reactive protein (CRP) level The primary endpoint was analyzed using non-responder imputation (NRI), i.e., subjects with missing ACR20 response at Week 12 were treated as non-responders.
ACR 20 response is defined as: * 20% improvement in tender joint count (TJC; 68 joints) relative to Week 0 AND * 20% improvement in swollen joint count (SJC; 66 joints) relative to Week 0 AND * 20% improvement in 3 of the following 5 areas relative to Week 0: * Subject's Assessment of Pain (100 mm - visual analogue scale \[VAS\]) * Subject's Global Assessment of Disease Activity (VASPA) * Physician's Global Assessment of Disease Activity (VASPHA) * Subject's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) * C-reactive protein (CRP) level The primary endpoint was analyzed using non-responder imputation (NRI), i.e., subjects with missing ACR20 response at Week 12 were treated as non responders.
| Arm | Type | Description |
|---|---|---|
| ALX-0061 150 mg q2w (+ MTX) | EXPERIMENTAL | - |
| ALX-0061 150 mg q4w | EXPERIMENTAL | ALX-0061 150 mg every 4 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit. |
| ALX-0061 150 mg q2w | EXPERIMENTAL | ALX-0061 150 mg every 2 weeks from baseline through Week 12 + placebo every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit. |
| ALX-0061 225 mg q2w | EXPERIMENTAL | ALX-0061 225 mg every 2 weeks from baseline through Week 12. The last injection with study drug was administered at the Week 10 visit. |
| TCZ 162 mg q1w or q2w | ACTIVE_COMPARATOR | Open-label TCZ. Injections were to be performed q1w or q2w depending on the approved label per region (last injection was administered at Week 10 or Week 11, depending on the dose regimen). |
| Placebo q2w + MTX | PLACEBO_COMPARATOR | Placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. |
| ALX-0061 75 mg q4w + MTX | EXPERIMENTAL | ALX-0061 75 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. |
| ALX-0061 150 mg q4w + MTX | EXPERIMENTAL | ALX-0061 150 mg every 4 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. |
| ALX-0061 150 mg q2w + MTX | EXPERIMENTAL | ALX-0061 150 mg every 2 weeks + placebo every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. |
| ALX-0061 225 mg q2w + MTX | EXPERIMENTAL | ALX-0061 225 mg every 2 weeks + MTX (at a stable dose and route) from baseline through Week 24. The last study drug administration was at the Week 22 visit. |
| ALX-0061 low dose i.v. | EXPERIMENTAL | - |
| ALX-0061 high dose i.v. | EXPERIMENTAL | - |
| ALX-0061 low dose s.c. | EXPERIMENTAL | - |
| ALX-0061 middle dose s.c. | EXPERIMENTAL | - |
| ALX-0061 high dose s.c. | EXPERIMENTAL | - |
| ALX-0061 | EXPERIMENTAL | - |
| Placebo | PLACEBO_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| ALX-0061 | BIOLOGICAL | Subjects received ALX-0061 150 mg s.c. injections, beginning at Week 0 and q2w thereafter, up to and including Week 102. Subjects from the preceding study ALX0061-C201 also continued their MTX treatment. |
| Placebo | BIOLOGICAL | - |
| Tocilizumab | BIOLOGICAL | - |
| Methotrexate | DRUG | Stable background dose of commercially available methotrexate (not provided by the Sponsor). |
Inclusion Criteria: * Must have been eligible for one of the preceding Phase IIb studies with ALX-0061 (study ALX0061-C201 or ALX0061-C202), have been randomized to placebo or one of the ALX-0061 arms (subjects randomized to tocilizumab \[TCZ\] in study ALX0061-C202 were not eligible), and complete...