Table 2.
Complement inhibitors in clinical trials for neurologic diseases.
| Complement inhibitors in clinical trials for neurologic diseases | ||||
|---|---|---|---|---|
| PHASE | DISEASE | INTERVENTION | RESULT/STATUS | CODE |
| Phase 2 | NMOSD | Eculizumab | At 12 months, 12/14 of treated patients’ relapse-free, median number of attacks decreased, visual acuity and disability improved | NCT00904826 |
| Phase 3 (PREVENT) | NMOSD | Eculizumab | 1ary endpoint of adjudicated relapse occurred in 3% (eculizumab) vs. 43% (placebo), time until 1st relapse increased, disability status improved | NCT01892345 |
| Phase 3 extension | NMOSD | Eculizumab | 96% of patients on eculizumab adjudicated relapse-free at 192 weeks. 95% no disability worsening and greater quality of life (QoL) | NCT02003144 |
| Phase 2/3 | Pediatric Participants, Relapsing NMOSD | Eculizumab | Recruiting | NCT04155424 |
| Phase 2/3 | Pediatric Participants, NMOSD | Ravulizumab | Not yet recruiting | NCT05346354 |
| Phase 3 | NMOSD | Ravulizumab | Active | NCT04201262 |
| Phase 1 | NMOSD | Cinryze (C1INH) as add-on | Completed, no adverse effects but insufficient efficacy. C1 activity inhibition in serum too low to confer clinical benefit | NCT01759602 |
| Phase 2 | Generalized myasthenia gravis (MG) | Eculizumab | 6/7 patients reached 1ary endpoint of 3-point reduction in Quantitative Myasthenia Gravis (QMG) score, QMG mean change significantly different | NCT00727194 |
| Phase 3 (REGAIN) | Generalized MG | Eculizumab | 1ary endpoint of MG-ADL mean ranked difference change not met but significant improvement in MG-ADL, QMG, MG-QoL15 sensitivity analysis. 2-3x more patients improved in eculizumab group | NCT01997229 |
| Phase 3 extension (ECU-MG-302) | Generalized MG | Eculizumab | MG exacerbation rate reduced by 75%, improvement in ADL, muscle strength, functional ability and QoL. 56% of treated patients achieved minimal manifestations | NCT02301624 |
| Phase 3 | Pediatric patients, generalized MG | Eculizumab | Active | NCT03759366 |
| Phase 3 | Generalized MG | Ravulizumab | Active | NCT03920293 |
| Phase 2 | Generalized MG | ALXN 2050 (Factor D Inh) | Recruiting. Goal >2 MG-ADL score reduction in consecutive 4 weeks | NCT05218096 |
| Phase 2 | GBS | Eculizumab + IVIg | 2/5 treated patients had 1-2 grade improvement on the GBS disability score | NCT02029378 |
| (ICA-GBS) | ||||
| Phase 2 | GBS | Eculizumab + IVIG | 1ary outcome, ability to walk independently 61% (eculizumab) vs. 45% (control), study did not reach predefined response rate | NCT02493725 |
| (JET-GBS) | ||||
| Phase 3 | Severe GBS | Eculizumab | Active. Goal assessment of efficacy and safety with Highest Functional Grade Scale | NCT04752566 |
| Phase 3 | ALS | Ravulizumab | Terminated (IDMC recommended to discontinue the trial due to ravulizumab lack of efficacy) | NCT04248465 |
| Phase 2 | ALS | Pegcetacoplan (APL-2), C3 inhibitor | Recruiting | NCT04579666 |
| Phase 2 (CIAO@TBI) | Traumatic Brain Injury (TBI) | C1 inhibitor | Recruiting | NCT04489160 |
| Phase 2 | Multifocal Motor Neuropathy | ARGX-117 (C3 inhibitor) | Recruiting | NCT05225675 |
| (ARDA) | ||||
| Phase 4 | Neurologic symptoms in post COVID-19 | Ruconest (C1 esterase inhibitor) | Recruiting | N+A3:E26CT04705831 |
Beyond NMOSD and MG, the use of complement inhibitors has been evaluated in GBS, ALS, TBI, Multifocal Motor Neuropathy and post-COVID19 neurologic symptoms.