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

NCT01171807 | Completed Phase 2 Results DMC

• 2 other identifiers: Crocodex2018-004763-31
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

Ulcerative Colitis

Keywords

Ulcerative colitis; Steroid-dependency; Steroid adverse events; Erythrocytes

Outcome Measures

Primary Outcomes (1)

• The Proportion of Patients Responders to Dex 21-P vs Placebo

  Patients were considered responder if, at the EoS, one of the following occurred: * Disease remission (Powell Tuck index ≤ 3 or CDAI \< 150) and withdrawal of oral steroids therapy from at least the second treatment procedure; * Disease marked improvement vs basal conditions (at least 5 point decrease in Powell Tuck or 150 point decrease in CDAI score) and withdrawal of oral steroids therapy from at least the second treatment procedure. The Powell-Tuck index was calculated by adding the subscores given by 7 items. A total score \< 10 indicated a mild activity of the UC, and a total score \>14 a severe one. The higher the score the worse the outcome. Crohn Disease Activity Index (CDAI) was a tool that combines subjective parameters, with objectives parameters. The score given to each parameter was inserted in an algorithm which provided the final Index value. A moderate CD showed a CDAI score between 220 and 450, while a CDAI \> 450 was an activity index indicating a severe disease.

  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 (6)

• Change From Baseline in Endogenous Cortisole Blood Level After Receiving the Study Treatment

  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)

• Change From Baseline in Inflammatory Indexes After Receiving the Study Treatment: Erythrocyte Sedimentation Rate (ESR)

  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)

• Change From Baseline in Inflammatory Indexes After Receiving the Study Treatment: C-reactive Protein (CRP)

  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)

• Count of Partecipants, Suffering From Mesalazine Refractory UC, With Modification in Endoscopic Result (Baron Score)

  From baseline to End of treatment = 28 weeks ± 5 days (in mesalazine refractory UC patients)

• Number of Patients Experiencing at Least One TEAE (Not Steroid-related)

  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)

Study Arms (2)

Dex 21-P

EXPERIMENTAL

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.

Drug: Dex 21-P

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Dex 21-P 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.

Also known as: Dexamethasone 21-phosphate

Dex 21-P

Placebo 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

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• More than 18 years of age
• 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.
• Disease extension over the rectum (at least 15 cm) in patients suffering from Ulcerative Colitis
• Patients willing and be able to give written informed consent.

You may not qualify if:

• Intestinal sub occlusion or a suspected abdomen abscess or a severe degree of the disease (CDAI \> 450) in patient suffering from Chron's Disease
• 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)
• 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)
• Treatment with Infliximab in the previous 4 months
• Pregnant woman or female for whom the possibility of a pregnancy during the study could not be excluded.

Sponsors & Collaborators

• Quince Therapeutics S.p.A.: lead
• Casa Sollievo della Sofferenza IRCCS: collaborator

Study Sites (1)

Casa Sollievo della Sofferenza Hospital

San Giovanni Rotondo, 71013, Italy

Location

Related Publications (1)

• 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.

  PMID: 23714676 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

dexamethasone 21-phosphate

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Results Point of Contact

• Title: Irene Maccabruni, M.Sc.
• Organization: Quince Therapeutics (former Erydel SpA)

imaccabruni@quincetx.com

+39 02 36504470

Study Officials

• Angelo Andriulli, MD

  Casa Sollievo della Sofferenza Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: No blinding procedures were applicable in this study which was designed as an open one.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2010
• First Posted: July 29, 2010
• Study Start: July 22, 2003
• Primary Completion: May 15, 2007
• Study Completion: May 15, 2007
• Last Updated: September 24, 2024
• Results First Posted: September 24, 2024

Record last verified: 2024-04

Locations

IT (1)