RPC4046, a Monoclonal Antibody Against IL13, Reduces Histologic and Endoscopic Activity in Patients With Eosinophilic Esophagitis.
- Hirano I Northwestern University Feinberg School of Medicine, Chicago, Illinois.
- Collins MH Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio.
- Assouline-Dayan Y Carver College of Medicine, Iowa City, Iowa.
- Evans L Grand Teton Research Group, Idaho Falls, Idaho.
- Gupta S University of Illinois College of Medicine, Peoria, Illinois.
- Schoepfer AM Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
- Straumann A Swiss EoE Clinic, University Hospital Zürich, Zürich, Switzerland.
- Safroneeva E Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
- Grimm M Celgene Corporation, Summit, New Jersey.
- Smith H Celgene Corporation, Summit, New Jersey.
- Tompkins CA Celgene Corporation, Summit, New Jersey.
- Woo A Celgene Corporation, Summit, New Jersey.
- Peach R Celgene Corporation, Summit, New Jersey.
- Frohna P Celgene Corporation, Summit, New Jersey.
- Gujrathi S Celgene Corporation, Summit, New Jersey.
- Penenberg DN Celgene Corporation, Summit, New Jersey.
- Li C Celgene Corporation, Summit, New Jersey.
- Opiteck GJ Celgene Corporation, Summit, New Jersey.
- Olson A Celgene Corporation, Summit, New Jersey.
- Aranda R Celgene Corporation, Summit, New Jersey.
- Rothenberg ME Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio.
- Dellon ES University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina. Electronic address: evan_dellon@med.unc.edu.
- 2018-11-06
Published in:
- Gastroenterology. - 2019
Esophagus
Immune Response
Placebo-Controlled
Randomized
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Biopsy, Needle
Dose-Response Relationship, Drug
Double-Blind Method
Drug Administration Schedule
Eosinophilic Esophagitis
Esophagoscopy
Female
Humans
Immunohistochemistry
Interleukin-13
Internationality
Male
Patient Safety
Reference Values
Severity of Illness Index
Treatment Outcome
English
BACKGROUND & AIMS
Eosinophilic esophagitis (EoE) is a chronic, esophageal, type 2 inflammatory response associated with increased serum levels of interleukin 13 (IL13), which might contribute to its pathogenesis. RPC4046, a recombinant humanized monoclonal antibody against IL13, prevents its binding to the receptor subunits IL13RA1 and IL13RA2. We performed a phase 2 trial to evaluate the efficacy and safety of RPC4046 in patients with EoE.
METHODS
We performed a multicenter, double-blind trial of 99 adults with active EoE randomly assigned (1:1:1) to groups given RPC4046 (180 or 360 mg) or placebo once weekly for 16 weeks, from September 2014 through December 2015. Patients were seen at day 1 (baseline) and weeks 2, 4, 8, 12, and 16. They underwent esophagogastroduodenoscopy and biopsies were collected at baseline and week 16. Patients completed a daily dysphagia symptom diary through week 16 and patient-reported outcome data were collected. The primary outcome was change in mean esophageal eosinophil count in the 5 high-power fields (hpfs) with the highest level of inflammation.
RESULTS
At week 16, mean changes in esophageal eosinophil count per hpf were a reduction of 94.8 ± 67.3 in patients who received 180 mg RPC4046 (P < .0001) and a reduction of 99.9 ± 79.5 in patients who received 360 mg RPC4046 (P < .0001) compared with a reduction of 4.4 ± 59.9 in patients who received placebo. The 360-mg RPC4046 group, compared with the placebo group, showed significant reductions in validated endoscopic severity score at all esophageal locations (P < .0001), validated histologic grade and stage scores (both P < .0001), and clinician's global assessment of disease severity (P = .0352); they had a numerical reduction in scores from the dysphagia symptom diary (P = .0733). Significant reductions in esophageal eosinophil counts and histologic and endoscopic features were observed in patients with steroid-refractory EoE who received RPC4046. The most common adverse events were headache and upper respiratory tract infection.
CONCLUSIONS
In a phase 2 trial of patients with EoE, we found RPC4046 (a monoclonal antibody against IL13) to reduce histologic and endoscopic features compared with placebo. RPC4046 was well tolerated. ClinicalTrials.gov no: NCT02098473.
Eosinophilic esophagitis (EoE) is a chronic, esophageal, type 2 inflammatory response associated with increased serum levels of interleukin 13 (IL13), which might contribute to its pathogenesis. RPC4046, a recombinant humanized monoclonal antibody against IL13, prevents its binding to the receptor subunits IL13RA1 and IL13RA2. We performed a phase 2 trial to evaluate the efficacy and safety of RPC4046 in patients with EoE.
METHODS
We performed a multicenter, double-blind trial of 99 adults with active EoE randomly assigned (1:1:1) to groups given RPC4046 (180 or 360 mg) or placebo once weekly for 16 weeks, from September 2014 through December 2015. Patients were seen at day 1 (baseline) and weeks 2, 4, 8, 12, and 16. They underwent esophagogastroduodenoscopy and biopsies were collected at baseline and week 16. Patients completed a daily dysphagia symptom diary through week 16 and patient-reported outcome data were collected. The primary outcome was change in mean esophageal eosinophil count in the 5 high-power fields (hpfs) with the highest level of inflammation.
RESULTS
At week 16, mean changes in esophageal eosinophil count per hpf were a reduction of 94.8 ± 67.3 in patients who received 180 mg RPC4046 (P < .0001) and a reduction of 99.9 ± 79.5 in patients who received 360 mg RPC4046 (P < .0001) compared with a reduction of 4.4 ± 59.9 in patients who received placebo. The 360-mg RPC4046 group, compared with the placebo group, showed significant reductions in validated endoscopic severity score at all esophageal locations (P < .0001), validated histologic grade and stage scores (both P < .0001), and clinician's global assessment of disease severity (P = .0352); they had a numerical reduction in scores from the dysphagia symptom diary (P = .0733). Significant reductions in esophageal eosinophil counts and histologic and endoscopic features were observed in patients with steroid-refractory EoE who received RPC4046. The most common adverse events were headache and upper respiratory tract infection.
CONCLUSIONS
In a phase 2 trial of patients with EoE, we found RPC4046 (a monoclonal antibody against IL13) to reduce histologic and endoscopic features compared with placebo. RPC4046 was well tolerated. ClinicalTrials.gov no: NCT02098473.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1053/j.gastro.2018.10.051
- PMID 30395812
- Persistent URL
- https://sonar.ch/global/documents/233222
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