Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
folate · 3 trials · 1 indication
Rate of progression in structural joint damage (PJD) by change in Total Modified Sharp Score (TMSS) from screening to Week 52 in the modified intent-to-treat (MITT) population. TMSS is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint erosions and joint space narrowing.
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.
A Grade III Adverse Event (AE) is severe; defined as considerable interference with the subject's daily activities, medical intervention/therapy required and hospitalization possible. A Grade IV AE is life-threatening; defined as extreme limitation in activity, significant medical intervention/therapy required, hospitalization probable. Because of the small sample size and the small number of subjects who completed Week 104, the analysis were limited to descriptive statistics only.
| Arm | Type | Description |
|---|---|---|
| Rituximab (0.5 g x 2) + Methotrexate | EXPERIMENTAL | Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6 |
| Rituximab (1.0 g x 2) + Methotrexate | EXPERIMENTAL | Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6 |
| Placebo + Methotrexate | PLACEBO_COMPARATOR | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. |
| 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. |
| 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. |
| 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. |
| Arm A: 500 mg Rituximab | EXPERIMENTAL | Rituximab: 1000 mg intravenous (IV) on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15-25 mg/wk oral or parenteral (10-14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk). |
| Arm B: 1000 mg Rituximab | EXPERIMENTAL | Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12.) For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15-25 mg/wk oral or parenteral (10-14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk). |
| Name | Type | Description |
|---|---|---|
| folate | DRUG | Intravenous repeating dose |
| methotrexate | DRUG | Oral or parenteral repeating dose |
| methylprednisolone | DRUG | Intravenous repeating dose |
| placebo | DRUG | Intravenous repeating dose |
| rituximab | DRUG | Intravenous repeating dose |
Inclusion criteria: * Adult patients 18-80 years of age * RA for ≥ 2 months; * Receiving outpatient treatment * Patients naive to, and considered to be candidates for, methotrexate treatment Exclusion criteria: * Rheumatic autoimmune disease other than RA, or significant systemic involvement seco...
Top 20 of 31 competitors
Folate is a small molecule being developed by Roche Holding AG for rheumatoid arthritis. It has been studied in Phase 3 clinical trials in patients with active rheumatoid arthritis, including studies where it was given in combination with methotrexate. The trials enrolled adults 18 years and older.
Folate is being developed by Roche Holding AG, which trades on the OTC market under the ticker RHHBY. Roche is the sponsor of the clinical trials evaluating folate in rheumatoid arthritis.
Folate is in Phase 3 clinical development for rheumatoid arthritis. Three trials have been completed, including two Phase 3 studies and one Phase 2 study. No trials are currently active. The drug has not been approved by the FDA for rheumatoid arthritis.
Folate has been evaluated in three completed clinical trials: NCT00299130, a Phase 3 study of rituximab with methotrexate versus methotrexate alone in 511 patients; NCT00299104, a Phase 3 study in methotrexate-naive patients with 755 participants; and NCT00243412, a Phase 2 study with 42 patients.
A total of 1,308 patients were enrolled across the three completed clinical trials of folate in rheumatoid arthritis. The trials were randomized, double-blind, and controlled, and included adults 18 years and older with active rheumatoid arthritis.