Table 3.
Clinical Trials of Biologics for the Treatment of HES*
| HES subtype |
Drug | Design** | Patient population | Dose | Outcome | Reference |
|---|---|---|---|---|---|---|
| PDGFRA-negative HES | mepolizumab | Ph 2 DBPC | Adults with GC-sensitive HES controlled on 20–50 mg prednisone (n=85) | 750 mg iv monthly | Met primary endpoint: proportion of subjects achieving prednisone dose ≤ 10 mg/ day × 8 weeks | 23,25 |
| Ph 2 OL | Adults with GC-sensitive HES controlled on 20–50 mg prednisone (n=78) | 750 mg iv; variable frequency | N/A | 24 | ||
| CUP | Prior participation in clinical trial of mepolizumab for HES OR Refractory, life-threatening HES | 300 mg sc–700 mg iv; variable frequency | Ongoing | NCT00244686 | ||
| Ph 3 DBPC | GC-responsive adults and children ≥12 years old with AEC ≥1000 on stable therapy (estimated n=120) | 300 mg sc monthly | Ongoing | NCT02836496 | ||
| reslizumab | Ph 2 OL | Adults with HES refractory to or intolerant of conventional therapy (n=4) | 1 mg/kg single dose | 2 of 4 subjects had reduction in eosinophilia | 20 | |
| benralizumab | Ph 2 DBPC/OL | Adults with HES and AEC ≥1000 despite background therapy (n=20) | 30mg sc monthly | Recently completed | NCT02130882 | |
| Overlap (EGPA) | mepolizumab | Ph 2 OL | Adults with active disease and on stable prednisolone dose > 12.5 mg for at least one week (n=7) | 750mg IV monthly | Met primary endpoint: percentage of subjects attaining remission | 38 |
| Ph 2 OL | Adults with EGPA requiring ≥10 mg/day prednisone (n=7) | 750mg IV monthly | Met primary endpoint: decreased prednisone dose at the end of treatment phase | 26 | ||
| Ph 3 DBPC | Adults with relapsing probable or definite EGPA requiring ≥ 7.5mg/day prednisone (n=136) | 300mg sc monthly | Met co-primary endpoints: accrued duration of remission and proportion of subjects in remission at week 36 and 48 | 27 | ||
| Reslizumab | Ph 2 OL | Adults with probable or definite EGPA on ≥5 mg/day of prednisone (estimated n=10) | 3 mg/kg monthly | Ongoing | NCT02947945 | |
| Benralizumab | Ph 2 OL | Adults with probable or definite EGPA on ≥5 mg/day of prednisone (estimated n=10) | 30mg sc monthly | Ongoing | NCT03010436 | |
| Rituximab | Ph3 DBPC | Adults with newly diagnosed or relapsing EGPA (estimated n=108) | No details | Ongoing | NCT02807103 | |
| Overlap (EGID) | Mepolizumab | Ph 2/3 OL | Adults with active EoE (peak eos > 20/hpf) (n=4) | 750mg IV monthly × 3 doses | Reduced blood and tissue eosinophils, improved symptoms (n=4) | 32 |
| Ph 2 DBPC | Adults with active EoE (peak eos > 20/hpf) (n=11) | 750mg IV weekly × 2 doses, then monthly × 2 if no response | Reduced blood and tissue eosinophils, no change in symptoms | 31 | ||
| Ph 2 DB | Children with active EoE (peak eos > 20/hpf) (n=59) | 0.55 mg/kg, 2.5 mg/kg, 10 mg/kg IV monthly × 3 doses | Reduction of tissue eosinophils, no significant effect on symptoms | 30 | ||
| Reslizumab | Ph 2 DBPC | Children with active EoE (peak eos> 24/hpf) (n=226) | 1 to 3 mg/kg monthly × 4 doses | Met one co-primary endpoint (reduction of tissue eosinophils), but symptoms improved in both drug and placebo groups | 29 | |
| Omalizumab | Ph 2 OL | Adults with active EoE (peak eos > 15 /hpf) and serum IgE 30–700 IU/mL who failed steroid therapy (n=30) | 0.016 mg/kg/IgE [IU/mL] every 2–4 weeks × 16 weeks | Did not meet primary endpoints: reduction in tissue eosinophilia and dysphagia score | 19 | |
| Dectrecumab (QAX576, anti-IL-13) | Ph 2 DBPC | Symptomatic adult EoE subjects who failed elimination diets (n=23) | 6 mg/kg IV every month × 3 months | Did not meet primary endpoint: proportion with ≥75% reduction in tissue eosinophils | 39 | |
| RPC4046 (anti-IL-13) | Ph 2 DBPC | Adult EoE subjects with symptoms (estimated n=100) | 1st dose IV, followed by low and high dose sc injections weekly × 16 weeks, then open label extension | Recently completed | NCT02098473 | |
| Dupilumab (anti-IL4Rα antagonist) | Ph 2 DBPC/OL | Adult EoE subjects with symptoms (n=47) | No details | Ongoing; enrollment complete | NCT02379052 |
*
Note: this list is based on a search of ClinicalTrials.gov and EudraCT on August 4, 2017 using the search terms “hypereosinophilic syndrome” or “eosinophilic disorders” and includes only phase 2 and 3 clinical trials.
**
DB – double-blind, PC - placebo-controlled; OL – open-label, CUP – compassionate use program