Intra-erythrocyte Dexamethasone Versus Placebo in Patients With Steroid-dependent Crohn's Disease

Phase 3

Terminated

• Conditions: Crohn's Disease
• Interventions: Drug: Dexamethasone

• Registration Number: NCT01277289
• Lead Sponsor: Quince Therapeutics S.p.A.

Brief Summary

Primary objective:

Assessment of the efficacy of EryDex vs PLACEBO in maintaining patients with steroid-dependent Crohn's disease in clinical remission throughout 12 months without oral steroids.

Secondary objectives:

1. safety of EryDex

2. emergence of new adverse effects from steroids or disappearance of those possibly pre-existing in the various subgroups of patients;

3. duration of the period of remission;

4. evaluation of the hypophysis-adrenal function;

5. study of plasma concentrations of dexamethasone;

6. effect of therapy on the metabolism of calcium and on indexes of inflammation;

7. assessing the quality of life;

8. rate of surgical resection

9. evaluation of the indirect costs of care.

Detailed Description

This was a multicenter, randomized, double-blind, PLACEBO-controlled, parallel-group study comparing EryDex versus PLACEBO. Patients with steroid-dependent Crohn's disease were enrolled and randomized to undergo 12 infusions of intraerythrocyte dexamethasone (EryDex), or PLACEBO. A balanced (1:1) randomization between the two treatment groups (EryDex / PLACEBO) was employed.

At the time of randomization, study patients were stratified at each study site according to their previous therapy with AZT/6MP/MTX (never treated with AZT/6MP/MTX or intolerant/resistant to the therapy with AZT/6MP/MTX). The treatment was planned to be performed with 12 monthly infusions of EryDex or PLACEBO.

Patients were followed-up after completion of the treatment for 6 months in patients regularly completing the study and 3 months in patients discontinuing from the study prematurely. The evaluation of the primary and secondary objectives was to be done at the 12th month of study (one month after the last study drug infusion), or upon relapse.

Study Timeline

• Study Start: 2009-06-03
• Study First Submitted: 2011-01-05
• Study First Submitted QC: 2011-01-13
• Study First Posted: 2011-01-14
• Primary Completion: 2011-12-30
• Study Completion: 2012-06
• Results First Submitted: 2022-06-01
• Status Verified: 2023-12
• Results First Submitted QC: 2023-12-15
• Last Update Submitted: 2023-12-15
• Results First Posted: 2024-06-03
• Last Update Posted: 2024-06-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 51

Inclusion Criteria

1. Male and female subjects;
2. Age > 18 years;
3. Patients with steroid-dependent Crohn's disease, documented in the medical history, having suffered from at least one episode of relapse (CDAI > 150) in the last 12 months. Patients should have been in clinical remission (CDAI < 150) for at least four weeks, on stable therapy with at least 10 mg of methylprednisolone (or equivalent), or been on steroidal tapering after a recent relapse. Patients with intolerance or resistance to AZT/6-MP/MTX were eligible;
4. Patients willing and able to give written informed consent.

Exclusion Criteria

1. Patients with Crohn's disease with intestinal sub-occlusion, or suspect of abdominal abscess, or with active perianal disease, or with clinically active disease at randomization (CDAI ≥150);

2. Patients already on therapy with immunosuppressant agents (AZT, 6-MP, MTX) for less than 4 months;

3. Patients having received therapy with infliximab (or other anti-TNF) in the previous 3 months;

4. Investigational treatments in the previous 3 months prior to randomization;

5. Pregnant women, or women who were not using valid birth-control measures, except those in surgical menopause; breast feeding;

6. Non collaborating subjects or those unable to be compliant with the treatment and the study schedules;

7. Severe concomitant diseases such as :

   1. patients with inadequate "bone marrow reserve": WBC < 3000 /mm3; PLTs < 75000 /mm3; Hb < 8 g/dl
   2. liver disease with total bilirubin ≥ 3 times the upper limit of normal (ULN), AST (GOT) ≥ 3x ULN, alkaline phosphatase ≥ 3x ULN
   3. renal disease with serum creatinine ≥ 3 mg/dl
   4. serious cardiac, allergic, lung, neurological diseases, neoplastic or pre-neoplastic disease
   5. diseases (other than Crohn's) requiring chronic steroid treatment;

8. Elective surgery already scheduled at the start of the study (NB: patients having undergone previous surgery for Crohn's disease could be enrolled, if the patient had fully recovered and had been in remission for at least 4 weeks);

9. Chronic use of alcohol; drug addiction;

10. Subjects with contra-indication to the use of steroids (i.e. systemic fungal infections);

11. Evidence of clostridium difficilis in the stools.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Dexamethasone	placebo comparator (sodium chloride instead of dexamethasone sodium phosphate) is administered in infusion at monthly interval.
Ery-dex	Dexamethasone	Ery-dex (dexamethasone sodium phosphate)is administered as intra-erythrocyte drug at monthly interval

Primary Outcome Measures

Name	Time	Method
Percentage of Patients Maintaining Steroids-free Clinical Remission (CDAI<150) Without Surgery for 12 Months	after 12 months	Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) \< 150. A therapy failure was considered to have occurred in patients with a CDAI score over 150 for \> 2 weeks and/or the need for systemic steroids (with / without surgery). Hence, the higher the index, the worse the outcome.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	after 12 months	This evaluation of safety was made by the comparison of treatment emergent adverse events (TEAE). Treatment emergent adverse events (TEAE) are undesirable events not present prior to medical treatment, or an already present event that worsens either in intensity or frequency following the treatment.
Percentage of Patients Interrupting the Study Because of Adverse Events	after 12 months	An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Duration of the Period of Steroid-free Clinical Remission	From end of the steroid therapy to relapse, up to 545 days	The mean time between the end of the steroid therapy and a confirmed relapse of the disease.
Dosing of Serum Cortisol	At Baseline and at the end of the study (18 months)	Levels of serum cortisol were measured at baseline and following Adrenocorticotropic Hormone (ACTH) trigger.

Trial Locations

Locations (8)

Spitalul Clinic Judetean De Urgenta; 🇷🇴 Cluj-Napoca, Romania

Ospedale Careggi; 🇮🇹 Firenze, Italy

Policlinico Sant'Orsola; 🇮🇹 Bologna, Italy

Ospedale Cervello; 🇮🇹 Palermo, Italy

Ospedale San Camillo; 🇮🇹 Rome, Italy

Complesso Integrato Columbus; 🇮🇹 Rome, Italy

A.O. San Donato; 🇮🇹 San Donato Milanese, Italy

Clinic CIBER EHD; 🇪🇸 Barcelona, Spain