Clinical trial NCT01171807: Erythrocytes-Mediated Delivery Of Dexamethasone 21-Phosphate In Steroid-Dependent Ulcerative Colitis
Official title: Dexamethasone Intra-Erythrocyte Therapy in Patients With Chron's Disease or Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ulcerative Colitis
Keywords: Ulcerative colitis
Steroid-dependency
Steroid adverse events
Erythrocytes
Lead sponsor: Quince Therapeutics S.p.A.
Sponsor class: INDUSTRY
Collaborators: name: Casa Sollievo della Sofferenza IRCCS
First posted: 2010-07-29
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Objectives:

The primary objective of this trial was to evaluate the patients response rate at the end of the study.

Patients were considered responder if one of the following conditions occurs:

* Disease remission (Powell Tuck ≤ 3 or CDAI \< 150) and withdrawal of oral steroids therapy from at least the second treatment procedure;
* Disease marked improvement versus basal conditions (at least 5 point decrease in Powell Tuck index or 150 point decrease in CDAI score) and withdrawal of oral steroids therapy from at least the second treatment procedure.

Secondary objectives:

* to evaluate the endogenous cortisole production after receiving the study treatment
* to evaluate the inflammatory indexes (ESR and CPR) after receiving the study treatment
* to evaluate the endoscopic remission in patients suffering from mesalazine refractory Ulcerative Colitis
* to evaluate the safety of dexamethasone intra-erythrocyte therapy with particular attention to steroid-related adverse events.

Detailed description: This was a single-center, placebo-controlled, randomised, phase II explorative study with the aim to investigate the ability of the new steroid delivery system to induce or maintain remission in steroid-dependent or mesalazine refractory patients suffering from Chron's disease (CD) or Ulcerative Colitis (UC) .

Once the patient was deemed eligible for the study, the treatment plan was selected as follows

In the Dexamethasone arm (DEX 21-P):

* steroid-dependant patients: one treatment procedure every 30 days up to a total of 6 procedures
* mesalazine refractory active UC patients: one treatment procedure every 15 days up to a total of 3 procedures.

In the placebo arm:

Patients assigned to placebo arm performed the same procedure as the patients assigned to the DEX 21-P group without loading in the Red Blood Cells the Dex 21-P.

The planned duration of individual patient participation in the study was a maximum of 6 or 28 weeks, depending from the assigned treatment scheme.

Eligibility criteria: Inclusion Criteria:

1. More than 18 years of age
2. Patients suffering from one of the following chronic inflammatory intestinal disease:

   * Steroid-dependent Chron's Disease or Ulcerative Colitis following ECCO definition or mild-moderate active UC ( Powell Tuck between 3 and 14- an index of 14 was allowed; endoscopic Baron score \>1) refractory to mesalazine.
3. Disease extension over the rectum (at least 15 cm) in patients suffering from Ulcerative Colitis
4. Patients willing and be able to give written informed consent.

Exclusion Criteria:

1. Intestinal sub occlusion or a suspected abdomen abscess or a severe degree of the disease (CDAI \> 450) in patient suffering from Chron's Disease
2. Patient affected by a severe Ulcerative Colitis (more than 6 evacuations of liquid, mucous-blooding stools combined at least one systemic sign as body temperature \> 37.8 °C, heart rate \< 90 bpm, ESR \> 30 mm/h or haemoglobin \< 10.5 g/dL)
3. Severe concurrent disease(s) as:

   * Medullar deficit: white blood cells \< 3000/mm3; platelets \< 75000/mm3; haemoglobin \< 10 g/dL;
   * Hepatic diseases presenting total bilirubin ≥ 3 mg/dL; AST (GOT) ≥ 5 UNL; alkaline phosphatase ≥ 5 UNL:
   * Renal failure with serum creatinine ≥ 3 mg/dL;
   * Heart failure
   * Respiratory failure
   * Disabling neurological diseases
   * Neoplasia
   * Patient deemed candidate to surgery due to Chron's Disease or Ulcerative Colitis
   * Chronic alcohol or drug abuse
   * Patient for whom the use of steroids is contraindicated (e.g. systemic infections)
4. Treatment with Infliximab in the previous 4 months
5. Pregnant woman or female for whom the possibility of a pregnancy during the study could not be excluded.
6. Non-collaborating patient or subject unable to regularly undergo the scheduled study procedures.

Primary outcomes:
measure: The Proportion of Patients Responders to Dex 21-P vs Placebo
timeFrame: From baseline to End of treatment = 6 weeks ± 10 days (in chronic and steroid dependent IBD patients) or 28 weeks ± 5 days (in mesalazine refractory UC patients)
Secondary outcomes:
measure: Change From Baseline in Endogenous Cortisole Blood Level After Receiving the Study Treatment
timeFrame: From baseline to End of treatment = 6 weeks ± 10 days (in chronic and steroid dependent IBD patients) or 28 weeks ± 5 days (in mesalazine refractory UC patients)
measure: Change From Baseline in Inflammatory Indexes After Receiving the Study Treatment: Erythrocyte Sedimentation Rate (ESR)
timeFrame: From baseline to End of treatment = 6 weeks ± 10 days (in chronic and steroid dependent IBD patients) or 28 weeks ± 5 days (in mesalazine refractory UC patients)
measure: Change From Baseline in Inflammatory Indexes After Receiving the Study Treatment: C-reactive Protein (CRP)
timeFrame: From baseline to End of treatment = 6 weeks ± 10 days (in chronic and steroid dependent IBD patients) or 28 weeks ± 5 days (in mesalazine refractory UC patients)
measure: Count of Partecipants, Suffering From Mesalazine Refractory UC, With Modification in Endoscopic Result (Baron Score)
timeFrame: From baseline to End of treatment = 28 weeks ± 5 days (in mesalazine refractory UC patients)
measure: Number of Patients Experiencing at Least One TEAE (Not Steroid-related)
timeFrame: From baseline to End of treatment = 6 weeks ± 10 days (in chronic and steroid dependent IBD patients) or 28 weeks ± 5 days (in mesalazine refractory UC patients)
measure: Number of Patients Experiencing at Least One TEAE (Steroid-related)
timeFrame: From baseline to End of treatment = 6 weeks ± 10 days (in chronic and steroid dependent IBD patients) or 28 weeks ± 5 days (in mesalazine refractory UC patients)
Other outcomes:
Locations:
city: San Giovanni Rotondo
country: Italy
facility: Casa Sollievo della Sofferenza Hospital
Study officials:
affiliation: Casa Sollievo della Sofferenza Hospital
name: Angelo Andriulli, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bossa F, Annese V, Valvano MR, Latiano A, Martino G, Rossi L, Magnani M, Palmieri O, Serafini S, Damonte G, De Santo E, Andriulli A. Erythrocytes-mediated delivery of dexamethasone 21-phosphate in steroid-dependent ulcerative colitis: a randomized, double-blind Sham-controlled study. Inflamm Bowel Dis. 2013 Aug;19(9):1872-9. doi: 10.1097/MIB.0b013e3182874065.