A Study to Evaluate the Efficacy and Safety of CC-93538 in Adult and Adolescent Participants With Eosinophilic Esophagitis

Eosinophilic Esophagitis Clinical Trial

Official title:

A Multi-Center, Multi-National, Randomized, Double-Blind, Placebo-Controlled Induction and Long-term Controlled Study to Evaluate the Efficacy and Safety of CC-93538 in Adult and Adolescent Subjects With Active Eosinophilic Esophagitis.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04753697
• Other study ID #: CC-93538-EE-001
• Secondary ID: U1111-1263-43512
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 22, 2021
• Est. completion date: October 2, 2024

Study information

• Verified date: January 2024
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study CC-93538-EE-001 is a Phase 3, multicenter, multinational, randomized, double-blind, placebo-controlled induction and maintenance study to evaluate the efficacy and safety of CC- 93538 in adult and adolescent participants with eosinophilic esophagitis (EoE). The study will incorporate a 24-week Induction Phase followed by a 24-week Maintenance Phase. Participants will be randomized at the beginning of the study into 3 treatment arms: - Placebo for Induction and Maintenance - CC-93538 360 mg Subcutaneous (SC) once weekly for Induction followed by 360 mg SC once every other week for Maintenance - CC-93538 360 mg SC once weekly for Induction and Maintenance

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 430
• Est. completion date: October 2, 2024
• Est. primary completion date: January 11, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 75 Years

Eligibility

Inclusion Criteria:

Participants must satisfy the following criteria to be enrolled in the study:

1. Male or female patients aged = 12 and = 75 years, with a body weight of > 40 kg.

2. Histologic evidence of eosinophilic esophagitis, defined as a peak count of = 15 eosinophils/high-power field at 2 levels of the esophagus. 3 Participant-reported history of 4 or more Dysphagia Days within 2 consecutive weeks prior to end of screening.

4. Lack of complete response to an adequate trial of proton pump inhibitor (8 weeks). Participants on a proton pump inhibitor must have been on a stable dose for at least 4 weeks prior to first Screening Visit and agree to continue the same dose throughout the study.

5. Participants currently receiving inhaled corticosteroids, leukotriene receptor antagonists, or mast cell stabilizers for indications other than EoE, or medium potency topical corticosteroids for dermatologic conditions, must maintain stable doses for at least 4 weeks prior to the first Screening Visit and throughout the duration of the study.

6. Participants must agree to maintain a stable diet (including any food elimination diet for the treatment of food allergy or eosinophilic esophagitis) and not introduce any changes in their diet from the first Screening Visit to the end of the study.

7. Females of childbearing potential must have 2 negative pregnancy tests as verified by the Investigator prior to starting study therapy and agree to practice a highly effective method of contraception until 5 months after the last dose. Exclusion Criteria:

The presence of any of the following will exclude a participant from enrollment:

1. Clinical or endoscopic evidence of other diseases that may affect the histologic, endoscopic, and clinical symptom evaluation for this study.

2. Other gastrointestinal disorders such as active Helicobacter pylori infection, esophageal varices, gastritis, colitis, celiac disease, Mendelian disorder associated with eosinophilic esophagitis, liver function impairment, or a known hereditary fructose intolerance.

3. Evidence of a severe endoscopic structural abnormality in the esophagus.

4. Esophageal dilation for symptom relief within 8 weeks prior to first Screening Visit or during the Screening Period, or if esophageal dilation is anticipated within 48 weeks of dosing during the study.

5. Evidence of immunosuppression, or of having received systemic immunosuppressive or immunomodulating drugs within 5 drug half-lives prior to the first Screening Visit.

6. Treatment with a high potency topical corticosteroid for dermatologic use, or a systemic corticosteroid within 8 weeks of the first Screening Visit.

7. Treatment with a swallowed topical corticosteroid, leukotriene receptor antagonist, or mast cell stabilizer for EoE, within 4 weeks of the first Screening Visit.

8. Treatment with oral or sublingual immunotherapy within 6 months of the first Screening Visit (any use will be prohibited during the study). Subcutaneous immunotherapy may be allowed if on stable doses for at least 3 months prior to the first Screening Visit and during the study.

9. Actively successful dietary modification adherence (e.g. food elimination diet), resulting in a complete response to EoE.

10. Prior treatment with CC-93538 during a Phase 1 or 2 clinical study.

11. Receipt of a live attenuated vaccine within 4 weeks of the first Screening Visit.

12. Any disease that would affect the conduct of the protocol or interpretation of the study results, or would put a patient at risk by participating in the study (e.g. severe uncontrolled asthma, infection causing eosinophilia, hypereosinophilic syndrome, or cardiovascular condition, or neurologic disorder or psychiatric illness that compromises the Participant's ability to accurately document symptoms of eosinophilic esophagitis).

13. Active or ongoing infections including parasitic/helminthic, hepatitis, tuberculosis, or human immunodeficiency virus.

14. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 4 weeks of the first Screening Visit.

15. Females who are pregnant or lactating.

Related Conditions & MeSH terms

• Eosinophilic Esophagitis
• Esophagitis

Intervention

Drug:
• CC-93538
Subcutaneous

Other:
• Placebo
Subcutaneous

Locations

Country	Name	City	State
Argentina	Local Institution - 697	Buenos Aires
Argentina	Local Institution - 695	Mar Del Plata
Argentina	Local Institution - 696	Quilmes
Australia	Local Institution - 552	Adelaide	South Australia
Australia	Local Institution - 553	Clayton	Victoria
Australia	Local Institution - 548	Concord	New South Wales
Australia	Local Institution - 545	Elizabeth Vale	South Australia
Australia	Local Institution - 538	Fitzroy
Australia	Local Institution - 543	Footscray	Victoria
Australia	Local Institution - 554	Liverpool	New South Wales
Australia	Local Institution - 546	Maroorchydore	Queensland
Australia	Local Institution - 539	Melbourne	Victoria
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Local Institution - 550	South Brisbane	Queensland
Australia	Local Institution - 547	Western Australia
Australia	Local Institution - 540	Westmead	New South Wales
Australia	Local Institution - 542	Woolloongabba	Queensland
Austria	Local Institution - 437	Burgenland
Austria	Local Institution - 434	Graz
Austria	Local Institution - 436	Linz
Belgium	Local Institution - 515	Brussels
Belgium	Local Institution - 516	Kortrijk
Belgium	Local Institution - 514	Leuven
Belgium	Local Institution - 512	West-Vlaanderen
Canada	Local Institution - 201	Calgary	Alberta
Canada	Local Institution - 205	Edmonton	Alberta
Canada	Local Institution - 208	Edmonton	Alberta
Canada	Local Institution - 207	Ottawa	Ontario
Canada	Local Institution - 203	Vancouver	British Columbia
Canada	Local Institution - 200	Vaughan	Ontario
Canada	Local Institution - 206	Victoria	British Columbia
Germany	Local Institution - 330	Bayern
Germany	Local Institution - 332	Brandenburg an der Havel
Germany	Local Institution - 339	Frankfurt am Main
Germany	Local Institution - 336	Hamburg
Germany	Local Institution - 333	Leipzig
Germany	Local Institution - 338	Leipzig
Germany	Local Institution - 337	Munchen
Germany	Local Institution - 340	München
Israel	Local Institution - 281	Haifa
Israel	Local Institution - 283	Holon
Israel	Local Institution - 280	Jerusalem
Israel	Local Institution - 282	Jerusalem
Israel	Local Institution - 278	Tel Aviv
Israel	Local Institution - 279	Zerifin
Italy	Local Institution - 257	Genova
Italy	Local Institution - 254	Milano
Italy	Local Institution - 255	Padova
Italy	Local Institution - 252	Pisa
Italy	Local Institution - 253	Rome
Japan	Local Institution - 593	Akita-shi
Japan	Local Institution - 595	Bunkyo-ku	Tokyo
Japan	Local Institution - 606	Isehara City, Kanagawa
Japan	Local Institution - 597	Kobe
Japan	Local Institution - 598	Maebashi
Japan	Local Institution - 604	Nagoya
Japan	Local Institution - 607	Nagoya
Japan	Local Institution - 592	Niigata-shi
Japan	Local Institution - 600	Nishinomiya	Hyogo
Japan	Local Institution - 603	Okayama-Shi
Japan	Local Institution - 591	Osaka
Japan	Local Institution - 599	Setagaya-ku	Tokyo
Japan	Local Institution - 601	Shibukawa
Japan	Local Institution - 602	Shinjuku-Ku
Japan	Local Institution - 605	Tokyo
Japan	Local Institution - 596	Toyoake
Japan	Local Institution - 590	Yamagata
Poland	Local Institution - 385	Bydgoszcz
Poland	Local Institution - 389	Czestochowa
Poland	Local Institution - 390	Gdansk
Poland	Local Institution - 388	Katowice
Poland	Local Institution - 392	Lódz
Poland	Local Institution - 383	Warsaw
Poland	Local Institution - 387	Warszawa
Poland	Local Institution - 393	Warszawa
Poland	Local Institution - 384	Wroclaw
Poland	Local Institution - 386	Wroclaw
Poland	Local Institution - 391	Wroclaw
Portugal	Local Institution - 305	Lisboa
Portugal	Local Institution - 307	Lisboa
Portugal	Local Institution - 306	Porto
Portugal	Local Institution - 308	Porto
Spain	Local Institution - 408	Barcelona
Spain	Local Institution - 410	Cordoba
Spain	Local Institution - 409	Madrid
Spain	Local Institution - 413	Madrid
Spain	Local Institution - 411	Marbella
Spain	Local Institution - 412	Sevilla
Switzerland	Local Institution - 357	Lausanne
United Kingdom	Local Institution - 228	Belfast Northern Ireland
United Kingdom	Local Institution - 231	Birmingham
United Kingdom	Local Institution - 234	Cardiff
United Kingdom	Local Institution - 235	Chorley
United Kingdom	Local Institution - 233	Hexam
United Kingdom	Local Institution - 236	Liverpool
United Kingdom	Local Institution - 237	Manchester
United Kingdom	Local Institution - 226	Southampton
United States	Local Institution - 139	Albuquerque	New Mexico
United States	Local Institution - 143	Anderson	South Carolina
United States	Local Institution - 043	Atlanta	Georgia
United States	Local Institution - 054	Atlanta	Georgia
United States	Local Institution - 171	Atlanta	Georgia
United States	Local Institution - 068	Aurora	Colorado
United States	Local Institution - 109	Baltimore	Maryland
United States	Local Institution - 003	Baton Rouge	Louisiana
United States	Dayton Gastroenterology, Inc	Beavercreek	Ohio
United States	Local Institution - 144	Birmingham	Alabama
United States	Local Institution - 053	Boston	Massachusetts
United States	Local Institution - 097	Boston	Massachusetts
United States	Local Institution - 101	Bristol	Connecticut
United States	Local Institution - 121	Casper	Wyoming
United States	Local Institution - 065	Catonsville	Maryland
United States	Local Institution - 105	Cedar Park	Texas
United States	Local Institution - 016	Chapel Hill	North Carolina
United States	Local Institution - 045	Charlotte	North Carolina
United States	Local Institution - 114	Chattanooga	Tennessee
United States	Local Institution - 039	Chicago	Illinois
United States	Local Institution - 001	Cincinnati	Ohio
United States	Local Institution - 006	Cincinnati	Ohio
United States	Local Institution - 052	Cincinnati	Ohio
United States	Local Institution - 099	Clearwater	Florida
United States	Local Institution - 072	Cleveland	Ohio
United States	Local Institution - 127	Clive	Iowa
United States	Local Institution - 067	Colorado Springs	Colorado
United States	Local Institution - 164	Columbia	Maryland
United States	Local Institution - 059	Columbus	Ohio
United States	Local Institution - 145	Columbus	Ohio
United States	Local Institution - 148	Dallas	Texas
United States	Local Institution - 092	Denver	Colorado
United States	Local Institution - 157	Draper	Utah
United States	Local Institution - 106	Durham	North Carolina
United States	Local Institution - 076	Farmington	Connecticut
United States	Local Institution - 046	Florence	Kentucky
United States	Local Institution - 034	Flowood	Mississippi
United States	Local Institution - 017	Framingham	Massachusetts
United States	Local Institution - 070	Glen Burnie	Maryland
United States	Local Institution - 028	Great Neck	New York
United States	Local Institution - 131	Greensboro	North Carolina
United States	Local Institution - 057	Greenville	South Carolina
United States	Local Institution - 167	Gurnee	Illinois
United States	Local Institution - 012	Hagerstown	Maryland
United States	Local Institution - 156	Hamden	Connecticut
United States	Local Institution - 120	Hershey	Pennsylvania
United States	Local Institution - 112	Houston	Texas
United States	Local Institution - 024	Idaho Falls	Idaho
United States	Local Institution - 118	Indianapolis	Indiana
United States	Local Institution - 036	Inverness	Florida
United States	Local Institution - 094	Iowa City	Iowa
United States	Local Institution - 042	Jacksonville	Florida
United States	Local Institution - 007	Kansas City	Missouri
United States	Local Institution - 035	Kansas City	Kansas
United States	Local Institution - 126	Kinston	North Carolina
United States	Local Institution - 075	Lancaster	California
United States	Local Institution - 015	Lebanon	New Hampshire
United States	Local Institution - 027	Leesburg	Virginia
United States	Local Institution - 170	Littleton	Colorado
United States	Local Institution - 047	Los Angeles	California
United States	Local Institution - 019	Louisville	Kentucky
United States	Local Institution - 013	Lynchburg	Virginia
United States	Local Institution - 117	Macon	Georgia
United States	Local Institution - 020	Metairie	Louisiana
United States	Local Institution - 044	Metairie	Louisiana
United States	Local Institution - 138	Miami	Florida
United States	Local Institution - 161	Miami	Florida
United States	Local Institution - 060	Milwaukee	Wisconsin
United States	Local Institution - 085	Milwaukee	Wisconsin
United States	Local Institution - 095	Nashville	Tennessee
United States	Local Institution - 011	New York	New York
United States	Local Institution - 051	New York	New York
United States	Local Institution - 154	New York	New York
United States	Local Institution - 165	North Little Rock	Arkansas
United States	Local Institution - 110	North Miami Beach	Florida
United States	Local Institution - 084	Oakland	California
United States	Local Institution - 125	Ogden	Utah
United States	Local Institution - 166	Oklahoma City	Oklahoma
United States	Local Institution - 038	Omaha	Nebraska
United States	Local Institution - 088	Orlando	Florida
United States	Local Institution - 133	Orlando	Florida
United States	Local Institution - 146	Orlando	Florida
United States	Local Institution - 025	Philadelphia	Pennsylvania
United States	Local Institution - 082	Phoenix	Arizona
United States	Local Institution - 147	Phoenix	Arizona
United States	Local Institution - 169	Pinellas Park	Florida
United States	Local Institution - 168	Plantation	Florida
United States	Local Institution - 115	Plymouth	Minnesota
United States	Local Institution - 037	Port Orange	Florida
United States	Local Institution - 155	Pottsville	Pennsylvania
United States	Local Institution - 066	Providence	Rhode Island
United States	Local Institution - 064	Richmond	Virginia
United States	Local Institution - 134	Roanoke	Virginia
United States	Local Institution - 049	Rochester	Minnesota
United States	Local Institution - 079	Rockwell	Texas
United States	Local Institution - 032	Saint Louis	Missouri
United States	Local Institution - 074	Salt Lake City	Utah
United States	Local Institution - 008	San Antonio	Texas
United States	Local Institution - 160	San Diego	California
United States	Local Institution - 041	Scottsdale	Arizona
United States	Local Institution - 083	South Dartmouth	Massachusetts
United States	Local Institution - 077	Southlake	Texas
United States	Local Institution - 137	Spokane	Washington
United States	Local Institution - 081	Springfield	Massachusetts
United States	Local Institution - 140	Sweetwater	Florida
United States	Local Institution - 116	Syracuse	New York
United States	Local Institution - 142	Syracuse	New York
United States	Local Institution - 098	Troy	Michigan
United States	Local Institution - 029	Tucson	Arizona
United States	Local Institution - 158	Tuscaloosa	Alabama
United States	Local Institution - 104	Tyler	Texas
United States	Local Institution - 023	Vancouver	Washington
United States	Local Institution - 128	Wheat Ridge	Colorado
United States	Local Institution - 009	Worcester	Massachusetts
United States	Local Institution - 014	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Canada,  Germany,  Israel,  Italy,  Japan,  Poland,  Portugal,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in DD Clinical Response	The mean change in dysphagia days (DD), evaluated over the prior 14-day period using the modified Daily Symptom Diary (mDSD), from baseline to Week 24	At week 24
Primary	Eosinophil Histologic Response (= 6/hpf)	The proportion of participants with eosinophilic histologic response defined as a peak esophageal eosinophil count = 6/high-power field (hpf) at Week 24	At week 24
Secondary	Eosinophil Histologic Response (< 15/hpf)	The proportion of participants with eosinophilic histologic response defined as a peak esophageal eosinophil count < 15/hpf at Week 24	At week 24
Secondary	EoE Endoscopic Reference Score (EREFS)	The mean change in the endoscopic features of eosinophilic esophagitis (EoE) as measured by the EoE Endoscopic Reference Score (EREFS) from baseline to Week 24	At week 24
Secondary	EoEHSS Grade Score	The mean change in the mean adjusted histology grade score as measured by the EoE histology scoring system (EoEHSS) from baseline to Week 24	At week 24
Secondary	EoEHSS Stage Score	The mean change in the mean adjusted histology stage score as measured by the EoE histology scoring system (EoEHSS) from baseline to Week 24	At week 24
Secondary	mDSD Composite Score	The mean change in the modified Daily Symptom Diary (mDSD) composite score from baseline to Week 24	At week 24
Secondary	DD Clinical Responder Definition	The proportion of participants with a = 50% decrease in dysphagia days (DD) from baseline at Week 24	At week 24
Secondary	Kinetics and Onset of Clinical Response_DD	The mean change in dysphagia days (DD) over time from baseline through Week 24	Through week 24
Secondary	Kinetics and Onset of Clinical Response_mDSD	The mean change in the modified Daily Symptom Diary (mDSD) composite score over time from baseline through Week 24	Through week 24
Secondary	Time to Event _EoE Flare	The time to event of Eosinophilic Esophagitis (EoE) flare during the Induction Phase	Through week 24
Secondary	Time to Event_Rescue Therapy	The time to event of use of rescue therapy during the Induction Phase	Through Week 24
Secondary	Proportion of Participants with Event-EoE Flare	The proportion of participants with an EoE flare during the Induction Phase	Through week 24
Secondary	Proportion of Participants with Event_Rescue Therapy	The proportion of participants with use of rescue therapy during the Induction Phase	Through week 24
Secondary	Incidence of Adverse Events (AEs)	An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE except for symptoms associated with an EoE flare requiring an EoE Flare Assessment	Through week 48
Secondary	Assessment of Immunogenicity through measurement of serum concentrations of anti-drug antibodies to CC-93538	Evaluated by the presence of anti-drug antibodies to CC-93538	Through week 48
Secondary	Pharmacokinetics- Ctrough	Serum trough concentration Measurements of trough concentrations of CC-93538 in participants with EoE during the Induction Phase	Through week 24
Secondary	Change in DD Clinical Response	The mean change in dysphagia days (DD), evaluated over the prior 14-day period using the modified Daily Symptom Diary (mDSD), from baseline to Week 48	At week 48
Secondary	Eosinophil Histologic Response (= 6/hpf)	The proportion of participants with eosinophilic histologic response defined as a peak esophageal eosinophil count = 6/high-power field (hpf) at Week 48	At week 48
Secondary	Eosinophil Histologic Response (< 15/hpf)	The proportion of participants with eosinophilic histologic response defined as a peak esophageal eosinophil count < 15/hpf at Week 48	At week 48
Secondary	Mean change in EREFS	The mean change in the endoscopic features of eosinophilic esophagitis (EoE) as measured by the EoE Endoscopic Reference Score (EREFS) from baseline to Week 48	At week 48
Secondary	EoEHSS Grade Score	The mean change in the mean adjusted histology grade score as measured by the EoE histology scoring system (EoEHSS) from baseline to Week 48	At week 48
Secondary	EoEHSS Stage Score	The mean change in the mean adjusted histology stage score as measured by the EoE histology scoring system (EoEHSS) from baseline to Week 48	At week 48
Secondary	mDSD Composite Score	The mean change in the modified Daily Symptom Diary (mDSD) composite score from baseline to Week 48	At week 48
Secondary	Time to event_EoE Flare (Induction and Maintenance Phase)	The time to event of EoE flare during the study	Through week 48
Secondary	Time to event_rescue therapy (Induction and Maintenance Phase)	The time to event of use of rescue therapy during the study	Through week 48
Secondary	Proportion of Participants with Event_EoE Flare (Induction and Maintenance Phase)	The proportion of participants with an EoE flare during the study	Through week 48
Secondary	Proportion of participants with event rescue therapy (Induction and Maintenance Phases)	The proportion of participants with use of rescue therapy during the study	Through week 48
Secondary	Pharmacokinetics-Ctrough	Measurements of trough concentrations of CC-93538 in participants with EoE during the Maintenance Phase	Through week 48

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting