Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Atacicept · 4 trials · 2 indications
An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Vital signs assessed included blood pressure (systolic and diastolic), pulse and body temperature. Routine safety lab parameters evaluated included red blood cell (RBC), hemoglobin, hematocrit, platelets, mean cellular hemoglobin (MCH), MCH concentration, MCH volume, white blood cell (WBC), lymphocytes, monocytes, eosinophils, basophils, neutrophils, gamma glutamyl transferase (GGT), alanine aminotransferase (ALT), albumin, alkaline phosphatase (AP), aspartate aminotransferase (AST), bilirubin, calcium, creatinine, glucose, potassium, total protein, sodium, uric acid, and blood urea nitrogen. Percent change from baseline was calculated as (\[Week 32 value minus baseline value\] multiplied by 100) divided by baseline value.
Percent change from baseline was calculated as (\[Week 32 value minus baseline value\] multiplied by 100) divided by baseline value.
Percent change from baseline was calculated as (\[Week 32 value minus baseline value\] multiplied by 100) divided by baseline value.
A flare was defined as having an adjudicated BILAG A or B score in any of the 8 organ systems during treatment, or imputed for participants who had premature treatment discontinuation. Discontinuations due to sponsor termination of the atacicept 150 mg group were not imputed as flares in this analysis. The BILAG disease activity index evaluates systemic lupus erythematosus (SLE) activity in 8 organ systems, using a separate alphabetic score (A to E) assigned to each organ system defined as follows. BILAG A: Disease sufficiently active requiring disease-modifying treatment (prednisone greater than 20 mg daily or immunosuppressants); BILAG B: Disease less active than in "A", mild reversible problems requiring only symptomatic therapy such as antimalarials, non-steroidal anti-inflammatory drugs (NSAIDs), or prednisone less than 20 mg day; BILAG C: Stable mild disease; BILAG D: System previously affected but now inactive; BILAG E: System never involved.
ACR20-CRP response is defined as greater than or equal to (\>=) 20 percent (%) improvement from Baseline in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with \>=20% improvement from Baseline in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP).
| Arm | Type | Description |
|---|---|---|
| Rituximab Plus Atacicept | EXPERIMENTAL | Rituximab will be administered as an intravenous infusion at a dose of 1000 mg at Weeks 1 and 3, followed by atacicept 150 mg subcutaneously once a week from Week 7 to 32. |
| Rituximab Plus Placebo | PLACEBO_COMPARATOR | Rituximab will be administered as an intravenous infusion at a dose of 1000 mg at Weeks 1 and 3, followed by placebo matched to atacicept subcutaneously once a week from Week 7 to 32. |
| Atacicept 75 mg | EXPERIMENTAL | - |
| Atacicept 150 mg | EXPERIMENTAL | - |
| Placebo | PLACEBO_COMPARATOR | - |
| Atacicept 150 mg with loading dose | EXPERIMENTAL | - |
| Atacicept 150 mg without loading dose | EXPERIMENTAL | - |
| Adalimumab | ACTIVE_COMPARATOR | - |
| Atacicept 25 mg | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Rituximab | BIOLOGICAL | Rituximab will be administered as an intravenous infusion at a dose of 1000 mg at Weeks 1 and 3. |
| Atacicept | DRUG | Atacicept will be administered at a dose of 150 mg subcutaneously once a week from Week 7 to 32. |
| Placebo matched to atacicept | DRUG | Placebo matched to atacicept will be administered subcutaneously once a week from Week 7 to 32. |
| Atacicept 75 mg | DRUG | 75 milligram (mg) atacicept injection will be administered subcutaneously twice weekly during initial loading period for 4 weeks followed by once weekly during maintenance period for subsequent 48 weeks. |
| Atacicept 150 mg | DRUG | 150 mg atacicept injection will be administered subcutaneously twice weekly during initial loading period for 4 weeks followed by once weekly during maintenance period for subsequent 48 weeks. |
| Placebo Comparator | OTHER | Placebo matched to atacicept injection will be administered subcutaneously twice weekly during initial loading period for 4 weeks followed by once weekly during maintenance period for subsequent 48 weeks. |
| Atacicept: with loading dose | DRUG | Atacicept will be administered subcutaneously at a dose of 150 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 21 weeks. |
| Adalimumab | BIOLOGICAL | Adalimumab (Humira®) will be administered subcutaneously at a dose of 40 mg every other week for 25 weeks. |
Inclusion Criteria: * Male and female subjects * Greater than and equal to (\>=) 18 years of age at the time of Informed Consent * Who have rheumatoid arthritis satisfying American College of Rheumatology (ACR) criteria with a disease history of at least 12 months * Subjects must have active diseas...
Atacicept is an investigational small molecule developed by Merck KGaA for immunology indications. It has been studied in systemic lupus erythematosus and rheumatoid arthritis. It is a TNFSF13B and TNFSF13 inhibitor. It is not approved and remains in clinical development, with completed Phase 2 trials in both conditions.
Atacicept has been studied in generalized systemic lupus erythematosus. The APRIL-SLE trial, NCT00624338, was a Phase 2/3 study that enrolled 461 participants with systemic lupus erythematosus across many countries. Atacicept is investigational and has not been approved for this or any other indication.
Atacicept targets TNFSF13B and TNFSF13. It acts as an inhibitor of these targets, which belong to the tumor necrosis factor ligand family. This target profile underlies its development as an immunology therapy for conditions such as systemic lupus erythematosus and rheumatoid arthritis.
Atacicept is developed by Merck KGaA, which trades under the ticker MKGAF. The company has sponsored the clinical trial program for the drug in immunology indications including systemic lupus erythematosus and rheumatoid arthritis.
Atacicept is in Phase 2 development. All four listed trials are Phase 2 studies, and all are completed. The drug is investigational and has not been approved by the FDA for any indication. No active trials are currently listed for Atacicept.
Atacicept has been evaluated in completed Phase 2 trials: NCT00664521 in rheumatoid arthritis with rituximab, NCT00624338 in systemic lupus erythematosus, NCT00595413 in anti-TNF alpha-naive rheumatoid arthritis, and NCT00430495, a dose-finding rheumatoid arthritis study. Total enrollment across these trials was 594 participants.