Study to evaluate the efficacy and safety of CC-93538 in adult and adolescent patients with eosinophilic esophagitis
Zusammenfassung der Studie
The standard of care in Switzerland is treatment with a proton pump inhibitor, corticosteroids, a dietary change, or an esophageal dilation procedure during the esophago-gastro-duodenoscopy. The tested substance, CC-93538 (or "Cendakimab"), is evaluated in individuals with various types of inflammatory conditions; one of which is eosinophilic esophagitis (inflammation of the esophagus). An eosinophil is a type of white blood cell. This research project aims to determine whether CC-93538 is safe and effective as a treatment for eosinophilic esophagitis. To do this, a comparison will be made between participants receiving CC-93538 as part of one of two different treatment plans and those receiving a placebo (a "treatment mimic") that looks like CC-93538 but is inactive. If you participate, you will be assigned by computer and randomly to one of three groups. We know little about CC-93538. The goal of this phase 3 study is to confirm results that suggest CC-93538 may be safe and effective in treating eosinophilic esophagitis. CC-93538 has not been approved by Swissmedic or other health authorities for this condition. Its use is therefore experimental, and all information is not clear about how the substance works in your body. The maximum duration of your participation in this international multicenter study is 72 weeks. The tested substance must be taken once a week and will consist of 2 subcutaneous injections with pre-filled syringes provided by the center, administered one after the other. The study is divided into 4 periods (a selection period of 4 to 8 weeks, an induction phase of 24 weeks, followed by a maintenance phase of 24 weeks and a safety monitoring period of 16 weeks).
(BASEC)
Untersuchte Intervention
Study treatments Participants will be randomized in a 1:1:1 ratio into the following treatment arms for the 24-week induction phase and the 24-week maintenance phase: • CC-93538 360 mg SC once a week for 24 weeks, followed by CC-93538 360 mg SC once a week for 24 weeks • CC-93538 360 mg SC once a week for 24 weeks, followed by CC-93538 360 mg SC once every 2 weeks for 24 weeks. During the maintenance phase, the corresponding placebo will be administered once every two weeks and then once a week, to maintain the blind • Corresponding SC placebo once a week for 24 weeks followed by corresponding SC placebo once a week for 24 weeks. The dose of CC-93538 360 mg SC will be administered by 2 injections of 1.2 ml, each provided in pre-filled syringes (SPR) of 150 mg/ml. The corresponding placebo will also be administered in the form of 2 injections of 1.2 ml.
(BASEC)
Untersuchte Krankheit(en)
Eosinophilic esophagitis (EO) is a chronic disease that affects nutritional intake and quality of life.
(BASEC)
•Male or female patients aged ≥ 18 years and ≤ 75 years, with a body weight > 40 kg. •Histological evidence of EO, defined as a peak in the count ≥ 15 eos/HPF at 2 levels of the esophagus. •Subject-reported history of 4 days of dysphagia or more in the 2 consecutive weeks prior to the end of selection. •No complete response to a trial of treatment with PPI (8 weeks). Subjects on PPI must have received a stable dose for at least 4 weeks prior to the first selection visit and agree to continue taking the same dose throughout the study. •Subjects currently receiving inhaled corticosteroids, leukotriene receptor antagonists, or mast cell stabilizers for indications other than EO or medium-potency topical corticosteroids for dermatological conditions must maintain stable doses for at least 4 weeks prior to the first selection visit and throughout the study. •Subjects must agree to maintain a stable diet (including any dietary elimination for the treatment of a food allergy or EO) and not introduce changes in their diet between the first selection visit and the end of the study. •Women of childbearing potential (WOCBP) must have 2 negative pregnancy tests verified by the investigator before starting study treatment and agree to use a highly effective method of contraception for up to 5 months after the last dose. (BASEC)
Ausschlusskriterien
•Clinical or endoscopic evidence of other diseases that may affect the assessment of histological, endoscopic, and clinical symptoms for this study. •Other GI disorders such as active Helicobacter pylori infection, esophageal varices, gastritis, colitis, celiac disease, a mendelian disease associated with EO, liver function insufficiency, or hereditary fructose intolerance. •Evidence of a severe structural anomaly in the esophagus at endoscopy. •Esophageal dilation aimed at relieving symptoms in the 8 weeks prior to the first selection visit or during the selection period or planned esophageal dilation within 48 weeks of product administration during the study. •Evidence of immunosuppression or patient who has received systemic immunosuppressants or immunomodulators within 5 half-lives of the drug prior to the first selection visit. •Treatment with a high-potency topical corticosteroid for dermatological use or with a systemic corticosteroid in the 8 weeks prior to the first selection visit. •Oral treatment with a topical corticosteroid, a leukotriene receptor antagonist, or a mast cell stabilizer for EO, in the 4 weeks prior to the first selection visit. •Treatment with oral, sublingual immunotherapy in the 6 months prior to the first selection visit (any use will be prohibited during the study). Subcutaneous immunotherapy may be allowed if administered at stable doses for at least 3 months prior to the first selection visit and during the study. •Active adherence to an effective dietary modification (e.g., elimination diet), resulting in a complete response to EO. •Previous treatment with CC-93538 during a phase 1 or 2 clinical study. •Receipt of a live attenuated vaccine in the 4 weeks prior to the first selection visit. (BASEC)
Studienstandort
Lausanne
(BASEC)
Sponsor
Celgene International II Sàrl Swiss representative: PPD Switzerland GmbH c/o Dufour Treuhand AG
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Natasa Dellaiacono
001 908 897-5652
NATASA.DELLAIACONO@clutterBMS.COMCelgene International II Sàrl
(BASEC)
Allgemeine Auskünfte
Bristol-Myers Squibb
(ICTRP)
Wissenschaftliche Auskünfte
Bristol-Myers Squibb
(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Waadt
(BASEC)
Datum der Bewilligung durch die Ethikkommission
22.02.2022
(BASEC)
ICTRP Studien-ID
NCT04753697 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
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 Subjects with Eosinophilic Esophagitis (BASEC)
Wissenschaftlicher Titel
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. (ICTRP)
Öffentlicher Titel
A Study to Evaluate the Efficacy and Safety of CC-93538 in Adult and Adolescent Participants With Eosinophilic Esophagitis (ICTRP)
Untersuchte Krankheit(en)
Eosinophilic Esophagitis (ICTRP)
Untersuchte Intervention
Drug: CC-93538;Other: Placebo (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Ein-/Ausschlusskriterien
Gender: All
Maximum age: 75 Years
Minimum age: 12 Years
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. (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Change in DD Clinical Response;Eosinophil Histologic Response (= 6/hpf) (ICTRP)
Eosinophil Histologic Response (< 15/hpf);EoE Endoscopic Reference Score (EREFS);EoEHSS Grade Score;EoEHSS Stage Score;mDSD Composite Score;DD Clinical Responder Definition;Kinetics and Onset of Clinical Response_DD;Kinetics and Onset of Clinical Response_mDSD;Time to Event _EoE Flare;Time to Event_Rescue Therapy;Proportion of Participants with Event-EoE Flare;Proportion of Participants with Event_Rescue Therapy;Incidence of Adverse Events (AEs);Assessment of Immunogenicity through measurement of serum concentrations of anti-drug antibodies to CC-93538;Pharmacokinetics- Ctrough;Change in DD Clinical Response;Eosinophil Histologic Response (= 6/hpf);Eosinophil Histologic Response (< 15/hpf);Mean change in EREFS;EoEHSS Grade Score;EoEHSS Stage Score;mDSD Composite Score;Time to event_EoE Flare (Induction and Maintenance Phase);Time to event_rescue therapy (Induction and Maintenance Phase);Proportion of Participants with Event_EoE Flare (Induction and Maintenance Phase);Proportion of participants with event rescue therapy (Induction and Maintenance Phases);Pharmacokinetics-Ctrough (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Bristol-Myers Squibb, Bristol-Myers Squibb (ICTRP)
Sekundäre IDs
U1111-1263-4351, 2020-004336-16, CC-93538-EE-001 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT04753697 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar