Principal Investigator: Kathryn Peterson
Keywords: CC-93538 , EoE , Esophagitis , Eosinophilic Esophagitis Department: Gastroenterology
IRB Number: 00140628
Specialty: Gastroenterology, Gastroenterology
Sub Specialties: Esophageal Diseases, Endoscopy
Recruitment Status: Not yet recruiting

Contact Information

Amy Holman
amy.holman@hsc.utah.edu
8015859155

Brief Summary

Primary Objectives
The primary objectives of the study are:
 To assess the efficacy of CC-93538 versus placebo in reducing dysphagia symptoms at 24
weeks
 To assess the efficacy of CC-93538 versus placebo in reducing esophageal eosinophil
counts at 24 weeks

Secondary Objectives
The secondary objectives are:
 To assess the efficacy of CC-93538 versus placebo at 24 weeks in improving:
 Endoscopic features of eosinophilic esophagitis (EoE)
 Histologic features of EoE
 To assess the persistence of effect of CC-93538 at 48 weeks in reducing:
 Dysphagia symptoms
 Esophageal eosinophil counts
 To assess the persistence of effect of CC-93538 through administration of a less frequent
dosing regimen at 48 weeks in reducing:
 Dysphagia symptoms
 Esophageal eosinophil counts
 To assess the persistence of effect of CC-93538 at 48 weeks in improving:
 Endoscopic features of EoE
 Histologic features of EoE
 To evaluate the time to and frequency of EoE flare events and use of rescue therapy during
the study
 To evaluate the safety and tolerability of CC-93538 including characterization of the
immunogenicity profile
 To assess trough concentrations of CC-93538 in subjects with EoE

Exploratory Objectives
The exploratory objectives are:
 To estimate improvements in subject rating of disease severity
 To estimate improvements in clinician rating of disease severity
 To estimate improvements in subject impression of change in EoE symptoms
 To estimate improvements in a patient-reported outcome measure of EoE symptoms
 To estimate improvements in a patient-reported outcome measure of EoE symptoms in
adolescent subjects
 To estimate improvements in additional EoE symptoms reported by subjects
 To estimate health-related quality of life
 To estimate work productivity
 To estimate health utility and overall health status
 To estimate the utilization of health care resources
 To conduct a population pharmacokinetic (PK) analysis to characterize the population PK
of CC-93538 and to evaluate the exposure-response or pharmacodynamics relationships
between dose (or concentration) and efficacy, safety, and biomarkers
 To explore the clinical profile of CC-93538 as a function of EoE biomarker expression
 To explore the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
serologic status on subjects receiving CC-93538, on EoE, and to support health authority
requests
 To estimate improvements in esophageal distensibility in subjects participating in the
EndoFLIP sub-study, if applicable

 

Inclusion Criteria

1. Subject must be ≥ 12 years and ≤ 75 years of age and have a body weight of ≥ 40 kg
(88.2 lb) at the time of signing the informed consent form (ICF)/assent form.
Note: Countries or sites with local restrictions that prohibit enrollment of adolescents
(aged 12 to 17 years inclusive) will only enroll subjects who are 18 years of age or older.
Enrollment of adolescent subjects will begin only after the applicable regulatory
requirements for enrolling subjects in that age group have been satisfied and the
necessary health authority approvals have been granted. Where national or regional
guidelines for the definition of adolescence differ from the definition stated above, the
national or regional guidelines may be used to determine eligibility.

2. Subject has histologic evidence of EoE, defined as a peak count of ≥ 15 eosinophils per
high-power field (hpf) at any 2 levels of the esophagus (proximal, mid, and/or distal)
when off anti-inflammatory therapy (eg, corticosteroids, see Exclusion Criterion 7) for
EoE. The histologic criterion for diagnosis of EoE must be confirmed by a centrally read
histological assessment of an EGD specimen during the Screening Period prior to
randomization.

3. Subject has symptoms of dysphagia of at least 4 DD, as assessed with the mDSD
instrument, over the last 2 consecutive weeks (14 days) prior to Day 1 when off antiinflammatory
therapy (eg, corticosteroids, see Exclusion Criterion 7) for EoE. Subjects
are required to have at least 11 days of diary data out of the final 14-day period of
screening mDSD collection in order to be enrolled in the study. During these 11 days,
responses to questions 2 through 5 of the mDSD instrument must be complete.

4. Subject must have previously received an adequate trial of proton-pump inhibitor (PPI)
medication (8 weeks per guidance, Dellon, 2013) that did not provide complete response
to EoE, or the subject remains symptomatic with continued use (Dellon, 2018b; Lucendo,
2017). Prospective subjects who discontinued use of a PPI must not have received a PPI
for at least 4 weeks before their first Screening Visit and must agree not to restart a PPI
during the study. If a prospective subject is receiving a PPI medication at screening, he
or she must have been receiving a stable dose for at least 4 weeks prior to the first
Screening Visit and agree to continue the same dose throughout the study.

5. Subject must either (1) be naïve or have had an adequate response to corticosteroid
therapy (ie, classified as Steroid Responders/Naïve) or (2) have had an inadequate
response to corticosteroid therapy and is not considered to be a candidate for continued
corticosteroid therapy, or is intolerant to corticosteroid therapy. For subjects who have
previously received systemic or swallowed topical corticosteroids for EoE, designation of
the status of Steroid Inadequate Responders/Intolerant will include either of the following
definitions. Note that if any of the below criteria are met, a subject will be deemed
Steroid Inadequate Responders/Intolerant (approximately 70% of the study population)
and cannot be classified as Steroid Responders/Naïve (approximately 30% of the study
population).
a. Inadequate response to corticosteroid therapy (failed to respond or lost response) and
not considered a candidate for continued corticosteroid therapy: subjects who have
had a trial of at least 6 weeks of swallowed topical corticosteroid treatment or
4 weeks of systemic corticosteroids at doses in accordance to published guidelines for
the management of EoE (Lucendo, 2017), or a trial for the treatment duration
specified in the prescribing information for approved products and judged by the
treating physician as not achieving clinical improvement or having clinical
improvement initially but lost response while on therapy.
b. Intolerant to corticosteroid therapy: subjects who initiated systemic or swallowed
topical corticosteroid treatment but were unable to achieve treatment durations or
dose levels due to intolerance because of side effects, including intolerance from use
of corticosteroids for conditions other than EoE, or subjects with underlying
conditions in which corticosteroid use is not recommended or contraindicated.
Documentation of type of therapy, treatment duration, and outcome details will be
collected when possible.

6. Subjects must agree to maintain a stable diet (including any food elimination diet for the
treatment of food allergy or EoE) from the first Screening Visit and throughout the
duration of the study, and subjects must have maintained a stable diet for at least 4 weeks
prior to the first Screening Visit. Subjects must agree not to introduce any changes in
their diet while participating in the study.

7. Subjects currently receiving inhaled corticosteroids, leukotriene receptor antagonists (eg,
montelukast), or mast cell stabilizers (eg, cromolyn sodium) for indications other than
EoE, or medium potency topical corticosteroids (eg, mometasone furoate cream or lotion)
for dermatologic conditions, must maintain stable doses/regimens for at least 4 weeks
prior to the first Screening Visit and regimens must remain stable throughout the duration
of the study. If recently discontinued, the medication must have been discontinued at
least 4 weeks prior to the first Screening Visit.

8. Female subjects of childbearing potential must agree to practice a highly effective
method of contraception. Highly effective methods of contraception are those that alone
or in combination result in a failure rate of a Pearl index of less than 1% per year when
used consistently and correctly.
A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at
some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out
childbearing potential) for at least 24 consecutive months (ie, has had menses at any time
in the preceding 24 consecutive months) and must:
a. Have 2 negative pregnancy tests as verified by the Investigator prior to starting study
therapy. She must agree to ongoing pregnancy testing during the course of the study
and through the Final 16-week Safety Follow-up Visit. This applies even if the
subject practices true abstinence* from heterosexual contact.
b. Either commit to true abstinence* from heterosexual contact (which must be reviewed
on a monthly basis and source documented) or agree to use, and be able to comply
with, highly effective contraception without interruption throughout the study and for
5 months after the last dose of IP. Acceptable methods of birth control in this study
are the following (birth control must be effective by the time the FCBP subject is
randomized into the study [eg, hormonal contraception should be initiated at least 28
days before randomization]):
 combined hormonal (estrogen and progestogen containing) contraception, which
may be oral, intravaginal, or transdermal
 progestogen-only hormonal contraception associated with inhibition of ovulation,
which may be oral, injectable, or implantable
 placement of an intrauterine device (IUD)
 placement of an intrauterine hormone-releasing system (IUS)
 bilateral tubal ligation; or bilateral tubal occlusion (if an implantable device was
recently placed, the subject must use an additional effective method of birth
control until full occlusion has been confirmed and documented)
 vasectomized partner (vasectomized partner is a highly effective birth control
method provided that the partner is the sole sexual partner of the FCBP and has
received medical assessment of the surgical success)
 sexual abstinence

9. Subject is willing to receive weekly SC injections throughout the study.

10. Subject must understand and voluntarily sign an ICF prior to any study-related
assessments/procedures being conducted. For subjects less than 18 years of age, subject
assent must be obtained, and parental/legal representative consent is required.

11. Subject is willing and able to adhere to the study visit schedule and other protocol
requirements

Exclusion Criteria

1. Subject has 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 study (eg, erosive esophagitis Los Angeles [LA] classification Grade B or above,
Barrett's esophagus, esophageal lichen planus, upper gastrointestinal bleed, achalasia,
inflammatory bowel disease, diagnosed eosinophilic gastroenteritis [clinical symptoms
and/or EGD findings and confirmatory eosinophilia in gastric and/or duodenal mucosa],
or significant hiatal hernia [> 3 cm], etc.).

2. Subject demonstrates presence of esophageal varices.

3. Subject has a known active Helicobacter pylori infection and/or is currently being treated
for this condition.

4. Subject has evidence of a severe endoscopic structural abnormality in the esophagus (eg,
high-grade stenosis where an 8- to 10-mm endoscope could not pass through the stricture
without dilation at the time of the screening EGD).

5. Subject had esophageal dilation for symptom relief during the Screening Period or within
8 weeks prior to the first Screening Visit, or esophageal dilation is anticipated to be
performed within 48 weeks of dosing during the study.

6. Subject demonstrates evidence of immunosuppression or is receiving systemic
immunosuppressive or immunomodulating drugs (eg, anti-IL-13 antibodies [except IP in
this study], IL-4 receptor alpha antagonist antibodies [eg, dupilumab], anti-IL-5
antibodies, anti-IL-17 antibodies, anti-immunoglobulin E [IgE] antibodies, α4β7 integrin
inhibitor antibodies, or any other monoclonal antibody, methotrexate, cyclosporine,
azathioprine, mercaptopurine, interferon alpha [IFNα], tumor necrosis factor alpha
[TNFα] inhibitors, etc.) within 5 drug half-lives prior to the first Screening Visit. Any
use of these medications will be prohibited during the study.

7. Subject is currently receiving systemic or swallowed topical corticosteroid medication.
Prospective subjects with EoE previously treated with a corticosteroid must not have
received a systemic corticosteroid within 8 weeks or swallowed topical corticosteroid
within 4 weeks of the first Screening Visit.

8. Subject is currently receiving a high potency topical corticosteroid (eg, augmented
betamethasone dipropionate, clobetasol propionate, etc.) for dermatologic use.
Prospective subjects must not have received a high potency topical corticosteroid for
dermatologic use within 8 weeks of the first Screening Visit. Any use will be prohibited
during the study.

9. Subject is currently receiving a leukotriene receptor antagonist (eg, montelukast) or mast
cell stabilizer (eg, cromolyn sodium) for the indication of EoE. Subjects must not have
received a leukotriene receptor antagonist or mast cell stabilizer for EoE within 4 weeks
of the first Screening Visit. Any use for the treatment of EoE during the study will be
prohibited.

10. Subject is currently successfully treated for EoE with dietary modifications (eg, food
elimination diet) and is able to fully adhere to the diet resulting in a complete response to
EoE (ie, the subject does not meet the symptoms of dysphagia requirement of at least 4
DD and histologic criterion for diagnosis of EoE per Section 4.2, Inclusion Criteria 2 and
3).

11. Subject has received oral or sublingual immunotherapy within 6 months of the first
Screening Visit; any use will be prohibited during the study. Subjects receiving SC
immunotherapy may participate but must be on stable doses for at least 3 months prior to
the first Screening Visit and during the study.

12. Subject is receiving concurrent treatment with another IP, including through participation
in an interventional trial for COVID-19. Prospective subjects may not participate in a
concurrent IP study or have received an IP within 5 drug half-lives prior to signing the
ICF/assent for this study. Further, for subjects who received an investigational
COVID-19 vaccine as part of a clinical trial prior to the first Screening Visit, enrollment
must be delayed until the biologic impact of the vaccine is stabilized, as determined by
discussion between the Investigator and the Clinical Trial Physician.

13. Subject has received a live attenuated vaccine within one month prior to the first
Screening Visit or anticipates the need to be vaccinated with a live attenuated vaccine
during the course of the study. Administration of any live attenuated vaccine will be
prohibited during the study through the Final 16-week Safety Follow-up Visit.

14. Subject has previously received CC-93538 treatment (formerly known as RPC4046 and
ABT-308) through participation in the Phase 2 Study, RPC02-201, or any Phase 1
clinical study.

15. Subject has any other disease that would make conduct of the protocol or interpretation of
the study results difficult or that would put the prospective subject at risk by participating
in the study (eg, severe uncontrolled asthma, infection causing eosinophilia,
hypereosinophilic syndrome, gastritis, colitis, celiac disease, Mendelian disorder
associated with EoE, or cardiovascular condition, or neurologic or psychiatric illness that
compromises the prospective subject's ability to accurately document symptoms of EoE).

16. Subject has liver function impairment or persisting elevations of aspartate
aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) or alanine
aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) that are 2 times the
upper limit of normal (ULN), or total bilirubin 1.5 times the ULN. Subjects with
elevations that are not clinically significant in total bilirubin associated with Gilbert’s
syndrome may participate.

17. Subject has an active parasitic/helminthic infection or a suspected parasitic/helminthic
infection. Subjects with suspected infections may participate if clinical and laboratory
assessments, if needed, rule out active infection prior to randomization.

18. Subject has an ongoing infection (eg, hepatitis B or C, human immunodeficiency virus
[HIV], or tuberculosis as defined by standard medical guidelines and as outlined in
Section 6.1).

19. Subject had a previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infection within 4 weeks prior to screening. Symptoms must have completely resolved
and based on Investigator assessment in consultation with the Clinical Trial Physician,
there are no sequelae that would place the participant at a higher risk of receiving
investigational treatment.

20. Subject has known hereditary fructose intolerance (HFI).

21. Subject is pregnant or lactating.

22. Subject has a history of idiopathic anaphylaxis or a major immunologic reaction (such as
anaphylactic reaction, anaphylactoid reaction, or serum sickness) to an immunoglobulin
G (IgG) containing agent.

23. Subject has a history of cancer or lymphoproliferative disease, other than a successfully
treated non-metastatic cutaneous squamous cell or basal cell carcinoma or adequately
treated cervical carcinoma in situ, within 5 years of screening.

24. Subject has a history of alcohol or drug abuse within 5 years prior to initiation of
screening.

25. Subject has any significant medical condition, laboratory abnormality, or psychiatric
illness that would prevent the subject from participating in the study.

26. Subject has any condition including the presence of laboratory abnormalities, which
places the subject at unacceptable risk if he/she were to participate in the study.

27. Subject has any condition that confounds the ability to interpret data from the study.