HEROES

Principal Investigator: Kathryn Peterson
Keywords: RPC02-201: A PHASE 2, MULTI-CENTER, MULTI-NATIONAL, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PARALLEL-GROUP CLINICAL TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF RPC4046 IN ADULT SUBJECTS WITH EOSINOPHILIC ESOPHAGITIS Department: Gastroenterology
IRB Number: 00075543 Co Investigator: Priyanka Kanth
Specialty: Gastroenterology
Sub Specialties: Esophageal Diseases
Recruitment Status: Active, not recruiting

Contact Information

Shannah Aleiwe
shannah.aleiwe@hsc.utah.edu
801-587-9050

Brief Summary

Receptos has chosen to develop RPC4046 for the treatment of EoE based on:

  • Strong preclinical support for a role for IL-13 in the pathophysiology of EoE
  • Evidence that RPC4046 was safe and well tolerated in the preceding Phase 1 clinical trial
  • Recognition of the potential benefits of RPC4046, an agent which prevents activation of both of the two IL-13 receptors

Phase 2 Clinical Trial RPC02-201 is the first trial in which RPC4046 will be administered to subjects with EoE.

The trial will utilize a standard randomized, double-blind, placebo-controlled, parallel arm design evaluating two doses of RPC4046 compared to placebo for 16 weeks. Subjects who complete the 16-week Double-Blind Treatment Period will have the option to receive the high dose of RPC4046 for an additional 52 weeks in an open-label extension (OLE) period to assess the durability of response and the longer-term safety of RPC4046.

Primary Trial Objective

The primary objective of the trial is to characterize the effect of RPC4046 on eosinophil counts in esophageal biopsy samples from subjects with symptomatic EoE.

Secondary Trial Objectives

The secondary objectives are:

  • To characterize the effects of RPC4046 on clinical symptoms of EoE
  • To characterize the effects of RPC4046 on EoE endoscopic score
  • To characterize the effects of RPC4046 on esophageal histologic findings
  • To characterize the safety and tolerability of RPC4046, including the development of anti-RPC4046 antibodies

Exploratory Trial Objectives

The exploratory objectives are to:

  • To characterize the effect of prior response to local corticosteroids on the local histology response and dysphagia clinical symptoms
  • To characterize biomarker responses
  • To characterize trough serum RPC4046 levels at two dose levels
  • To evaluate the pharmacodynamic relationships between dose/concentration and the efficacy parameters
  • To characterize the long-term effects of RPC4046 on clinical symptoms, endoscopic scores, esophageal histologic findings and safety during the OLE

 

  1. Sub-Study Objective (at a subset of participating sites)
    • To assess esophageal distensibility using a Functional Luminal Imaging Probe (FLIP)

Inclusion Criteria

Inclusion Criteria
To be eligible to participate in this trial, candidates must meet the following inclusion criteria:
1. Males and females 18 to 65 years of age (inclusive) with symptoms of EoE at the first
screening visit. Diagnosis of EoE must be confirmed prior to randomization 
2. Symptoms of dysphagia (i.e., at least 4 dysphagia days − as assessed with a daily symptom
diary − over the last 2 consecutive weeks [±3 days] prior to Day 1) when off antiinflammatory
therapy for EoE
3. Histologic evidence of EoE defined as a peak count of ≥15 eosinophils per hpf at any 2 levels
of the esophagus when off anti-inflammatory therapy for EoE
4. Must have previously received an adequate trial of PPI medication that ruled out
gastroesophageal reflux disease (GERD) and PPI-responsive esophageal eosinophilia (PPIREE)

as the primary cause of their symptoms. Subjects with a partial response to PPI who

meet all other eligibility criteria may be enrolled. Prospective subjects who discontinued use

of a PPI must wait at least 4 weeks before their screening endoscopy. If a prospective subject

is receiving a PPI at screening, they must have been receiving a stable dose for at least 4
weeks prior to the screening endoscopy and agree to continue on a the same dose through
Week 16
5. Males and females of childbearing potential must agree to use adequate birth control
measures during the trial and for 5 months after their last dose of trial treatment. Acceptable
methods of birth control in this trial include: surgical sterilization, intrauterine device, oral
contraceptive, contraceptive patch, long acting injectable contraceptive, subject’s or partner’s
vasectomy, double-barrier method (condom or diaphragm with spermicide) or abstinence
6. All females of childbearing potential must have a negative serum pregnancy test at screening
and a negative urine (or serum) pregnancy test prior to dosing on Day 1.
7. Ability to provide written informed consent and to be compliant with the schedule of
protocol assessments
8. Ability to read and understand English (in order to be able to complete the clinical symptom
PRO questionnaires, which are written in English)
9. Willing to receive weekly SC injections through at least Week 15

Exclusion Criteria

Exclusion Criteria
Candidates will be excluded from trial entry if any of the following exclusion criteria exist at
time of randomization:
1. Clinical or endoscopic evidence of the presence of any other disease that may interfere
with or affect the histologic, endoscopic, and clinical symptom endpoints for this trial
(e.g., erosive esophagitis Grade 2 or above, Barrett’s disease, upper gastrointestinal
bleed, eosinophilic gastritis or gastroenteritis, duodenal or gastric eosinophilia on
screening endoscopy, inflammatory bowel disease, significant hiatal hernia [> 3 cm],
etc.)
2. Presence of esophageal varices
3. Evidence of severe endoscopic structural abnormality in esophagus (e.g., high-grade
stenosis where an 8−10 mm endoscope could not pass through the stricture without
dilation at the time of endoscopy)
4. Primary causes of esophageal eosinophilia other than EoE
5. Evidence of immunosuppression or receiving systemic immunosuppressive or
immunomodulating drugs (e.g., methotrexate, cyclosporine, interferon alpha [IFNα],
tumor necrosis factor alpha [TNFα] inhibitors, antibodies to immunoglobulin E [IgE],
etc.) within 5 drug half-lives prior to screening
6. Receiving systemic or swallowed topical corticosteroid medication. Prospective subjects
with EoE treated with a corticosteroid, must have not received a systemic corticosteroid
within 8 weeks or swallowed topical corticosteroids within 4 weeks of the screening
endoscopy or the start of the daily clinical symptom diary data collection during
screening, whichever is performed first
7. Presence of any other disease making conduct of the protocol or interpretation of the trial
results difficult or that would put the prospective subject at risk by participating in the
trial (e.g., infection causing eosinophilia; gastritis, colitis, irritable bowel syndrome, and
celiac disease which have similar symptoms; neurologic or psychiatric illness that
compromises the prospective subject’s ability to accurately document symptoms of EoE,
etc.)
8. Liver function impairment or persisting elevations of aspartate aminotransferase (AST) or
alanine aminotransferase (ALT) > 2 times the upper limit of normal (ULN), or direct
bilirubin > 1.5 times the ULN
9. Systemic or diarrheal illness following travel or residence in endemic areas of
parasitic/helminthic infections; history of clinical schistosomiasis, history of travel to
endemic areas within preceding 6 months
10. Ongoing infection (e.g., hepatitis B or C, human immunodeficiency virus [HIV], active
tuberculosis)
11. Pregnancy or lactation
12. Concurrent treatment with another investigational drug. Prospective subjects may not
participate in a concurrent investigational drug trial or have received an investigational
drug within 5 drug half-lives prior to signing the informed consent form for this trial
13. Weight less than 40 kg (88.2 pounds) or greater than 125 kg (275 pounds)
14. History of idiopathic anaphylaxis or a known history of a major immunologic reaction
(such as anaphylactic reaction, anaphylactoid reaction, or serum sickness) to an IgGcontaining
agent
15. History of cancer or lymphoproliferative disease, other than a successfully treated nonmetastatic
cutaneous squamous cell or basal cell carcinoma or adequately treated cervical
carcinoma in situ, within 10 years of screening
16. Esophageal dilation for symptom relief during the screening period and within 4 weeks
prior to baseline assessment of dysphagia or anticipated to be performed during the study