Table 1.
Clinical Trials of SLE Drugs by Targeted Immune Cell or Mechanism of Action from 2005 to 2020
| Drug | ClinicalTrials.gov Identifier a | Mechanism of Action | Study Design b | Status | Primary Outcome Measure(s) |
|---|---|---|---|---|---|
| Immune Complexes | |||||
| RSLV-132 | NCT02194400 | Fc fused to RNase | RC, PC, DB | Completed phase 1 | Number of participants with treatment-related adverse events |
| RSLV-132 | NCT02660944 | Fc fused to RNase | RC, PC, DB | Recruitment status unknown, phase 2a | Proportion of participants with CLASI improvement compared to placebo at week 24 |
| Plasmacytoid Dendritic Cells and Type I Interferon | |||||
| BIIB059 | NCT02847598 (LILAC) | Anti-BDCA2 | PC, RC, DB | Completed phase 2 | Change in baseline active joint count at week 24; Change from baseline CLASI-A score at week 16 |
| BIIB059 | NCT02106897 | Anti-BDCA2 | PC, RC | Completed phase 1 | Adverse Events and Serious Adverse Events at week 32 |
| Anifrolumab | NCT01438489 (MUSE) | Anti-IFNAR subunit 1 | PC, RC, DB, MC | Completed phase 2 | SRI at week 24 with sustained oral corticosteroid reduction |
| Anifrolumab | NCT02446899 (TULIP-2) | Anti-IFNAR subunit 1 | PC, RC, DB | Completed phase 3 | BICLA response at week 52 |
| Anifrolumab | NCT02446912 (TULIP-1) | Anti-IFNAR subunit 1 | PC, RC, DB, MC | Completed phase 3 | SRI ≥4 at week 52 |
| IFN-α kinoid | NCT02665364 | Inactivated IFNα2b coupled to a carrier protein | PC, RC, DB | Active, not recruiting phase 2b | Change in IFN gene signature at week 36; BICLA with corticosteroid taping at week 36 |
| B Cells | |||||
| Rituximab | NCT00137969 (EXPLORER) | Anti-CD20 | PC, RC, DB, MC | Completed phase 2/3 | Major, partial, or no clinical response based on BILAG scores from baseline to week 52 |
| Rituximab | NCT00282347 (LUNAR) | Anti-CD20 | PC, RC, DB, MC | Completed phase 3 | Complete, partial or no renal response at week 52 |
| Obinutuzumab | NCT02550652 (NOBILITY) | Anti-CD20 | PC, RC, DB, MC | Active, not recruiting phase 2 | Complete renal response at week 52 |
| Abatacept | NCT00430677 | Recombinant CTLA4-Ig fusion protein | MC, RC, DB, PC | Terminated phase 2/3 | Time to confirmed complete renal response from day 1 to 12 months |
| Cytokines | |||||
| Belimumab | NCT00410384 (BLISS-76) | Anti-BLyS | MC, RC, DB, PC | Completed phase 3 | SRI-4 response rate at week 52 |
| Belimumab | NCT00424476 (BLISS-52) | Anti-BLyS | MC, RC, DB, PC | Completed phase 3 | SRI response rate at week 52 |
| Belimumab | NCT01639339 (BLISS-LN) | Anti-BLyS | RC, DB, PC | Completed phase 3 | Primary Efficacy Renal Response at week 104 |
| Telitacicept (RC18) | NCT02885610 | Recombinant fusion protein targeting APRIL and BLyS | PC, MC, RC, DB | Completed phase 2b | SRI-4 response rate at week 48 |
| Ustekinumab | NCT02349061 | Monoclonal antibody targeting IL-12 and IL-23 | MC, RC, DB, PC | Completed phase 2 | SRI-4 composite response at week 24 |
| Ustekinumab | NCT03517722 (LOTUS) | Monoclonal antibody targeting IL-12 and IL-23 | RC, DB, PC | Discontinued phase 3 | SRI-4 composite response at week 52 |
| hrIL-2 active | NCT02465580 | Low-dose human recombinant IL-2 | DB, RC, PC | Recruitment status unknown, phase 2 | SLEDAI-4 responders at week 24 |
| Voclosporin | NCT03021499 (AURORA) | Calcineurin inhibitor | RC, DB, PC | Completed phase 3 | Renal response at week 52 |
| Cell Signaling | |||||
| Baricitinib | NCT02708095 | JAK 1/2 inhibitor | RC, DB, PC | Completed phase 2 | Remission of arthritis and/or rash defined by SLEDAI-2K at week 24 |
| Baricitinib | NCT03616912 (BRAVE I) | JAK 1/2 inhibitor | RC, BD, PC | Recruiting phase 3 | SRI-4 response at week 52 |
| Baricitinib | NCT03616964 (BRAVE II) | JAK 1/2 inhibitor | RC, BD, PC | Recruiting phase 3 | SRI-4 response at week 52 |
| Tofacitinib | NCT02535689 | JAK 1/2/3 inhibitor | DB, RC, PC | Completed phase 1b | Safety in SLE participants after 5 years |
| BMS-986165 | NCT03252587 (PAISLEY) | Anti-TYK2 | RC, DB, PC | Recruiting phase 2 | Response criteria of SRI-4 at week 32 |
| Metformin | NCT02741960 | AMPK activation | MC, RC, DB, PC | Completed phase 4 | SELENA-SLEDAI Flare Index at 12 months |
| Combination Therapies | |||||
| Rituximab followed by belimumab | NCT03312907 (BLISS-BELIEVE) | Anti-BLyS and anti-CD20 | MC, RC, DB, PC | Active, not recruiting phase 3 | SLEDAI-2K score <=22 at week 52 |
| Rituximab followed by belimumab | NCT02260934 (CALIBRATE) | Anti-BLyS and anti-CD20 | RC, MC, OL | Completed phase 2 | Infectious adverse event at week 24, 48, and 96 |
a
Studies are registered at https://clinicaltrials.gov/ct2/
b
Abbreviations: PC, placebo controlled; RC, randomized; DB, double blind; MC, multi-center; OL, open label; CLASI-A, Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity; BICLA, British Isles Lupus Assessment Group Based Composite Lupus Assessment; SRI, Systemic Lupus Erythematosus (SLE) Responder Index; BILAG, British Isles Lupus Assessment Group; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000; SELENA, Safety of Estrogens in Lupus Erythematosus – National Assessment