Erythrocytes-Mediated Delivery Of Dexamethasone 21-Phosphate In Steroid-Dependent Ulcerative Colitis

NCT ID: NCT01171807

Last Updated: 2024-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-07-22
• Study Completion Date: 2007-05-15

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.

Conditions

Ulcerative Colitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dex 21-P

In this arm a dose of 20 ml of Dex 2-P solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively.

Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval.

Every procedure implies the collection and re-infusion of autologous erythrocytes previously loaded with Dex 21-P.

Group Type: EXPERIMENTAL

Dex 21-P

Intervention Type: DRUG

At each procedure 50 ml of patient whole blood was washed with saline solution and centrifugated. The isolated erythrocytes were suspended into 2 hypotonic solutions to make their membrane permeable and incubated with Dex 21-P sodium salt up to obtain a final concentration of 10 mM. The drug loaded erythrocytes were immediately re-infused by using a suitable filter.

Placebo

In this arm placebo solution was administered every 15 or 30 days for a total of 3 or 6 treatment procedures, respectively.

Specifically, steroid-dependant IBD patients had to undergo a total of 6 procedures at one month interval, while active mesalazine refractory UC patients had to undergo a total of 3 procedures at 15 days interval.

Every procedure implies the collection and re-infusion of autologous erythrocytes previously NOT loaded with Dex21-P.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Dex 21-P

At each procedure 50 ml of patient whole blood was washed with saline solution and centrifugated. The isolated erythrocytes were suspended into 2 hypotonic solutions to make their membrane permeable and incubated with Dex 21-P sodium salt up to obtain a final concentration of 10 mM. The drug loaded erythrocytes were immediately re-infused by using a suitable filter.

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

Dexamethasone 21-phosphate

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Casa Sollievo della Sofferenza IRCCS

OTHER

Sponsor Role: collaborator

Quince Therapeutics S.p.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Angelo Andriulli, MD

Role: PRINCIPAL_INVESTIGATOR

Casa Sollievo della Sofferenza Hospital

Locations

Casa Sollievo della Sofferenza Hospital

San Giovanni Rotondo, , Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 23714676 (View on PubMed)

Other Identifiers

2018-004763-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Crocodex

Identifier Type: -

Identifier Source: org_study_id