Back to results

Pilot Efficacy and Safety Study of Oral DF2156A in Patients With Active Bullous Pemphigoid

Primary Purpose

Bullous Pemphigoid

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

DF2156A

About this trial

This is an interventional treatment trial for Bullous Pemphigoid focused on measuring Autoimmune inflammatory blistering disorder

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male and female patients aged >50 years.
Patients with newly diagnosed or relapsing bullous pemphigoid based on clinical diagnosis to be confirmed by direct immunofluorescence and indirect immunofluorescence on salt-spit skin (or BP180 and/or BP230 ELISA). Confirmation by laboratory tests will be obtained ideally before or anyway within one week after enrolment.

For the purpose of this study, clinical relapses are defined as re-appearance of clinical symptoms after the patient had attained remission lasting for more than 3 months without immunosuppressive treatment. In patients with relapsing BP, clinical diagnosis will be confirmed by indirect immunofluorescence or BP180 and/or BP230 ELISA only.

Patients with mild to moderate active blistering disease (total number of blisters between 1 and 30) whether associated or not with urticarial/eczematous lesions.
Patients with modified ABSIS score ≤50
Patients free from any systemic treatments that may affect the course of the disease with the following off-period prior to enrolment:
1. 3 weeks: steroids, dapsone, tetracyclines, nicotinamide,
2. 3 months: azathioprine, mycofenolate mofetil, cyclophosphamide, methotrexate, intravenous immunoglobulins, immunoadsorption, TNF antagonists
3. 12 months: rituximab, leflunomide
Patients free from any topical treatments other than topical antibiotics and antiseptics in the 4 days prior to enrolment.
Patients able to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations.
Patients able to provide informed consent.

Exclusion Criteria:

Patients with a Karnofsky rating score <40%.
Patients with mucosal involvement.
Patients with moderate to severe renal impairment as per calculated creatinine clearance (CLcr) < 50 mL/min according to the Cockcroft-Gault formula (Cockcroft-Gault , 1976).
Patients with hepatic dysfunction defined by increased ALT/AST > 3 x upper limit of normal (ULN) and increased total bilirubin > 3 mg/dL [>51.3 μmol/L].
Patients with hypoalbuminemia defined as serum albumin < 3 g/dL.
Patients with a baseline (day 0/1, pre-dose) QTcF > 470 msec.
Patients who had a myocardial infarction in the 6 months prior to enrolment.
Patients on treatment with phenytoin, warfarin, sulphonylurea hypoglycemics (e.g. tolbutamide, glipizide, glibenclamide/glyburide, glimepiride, nateglinide) and high dose of amitriptyline (> 50 mg/day).
Patients with known hypersensitivity to non-steroidal antiinflammatory drugs.
Patients using any investigational agent within 12 months prior to enrolment.
Pregnant or breast feeding women. Unwillingness to use effective contraceptive measures up to 2 months after the end of study drug administration (females and males).

Additional Exclusion Criteria for Germany only:

Patients with hypokalemia defined as serum potassium < 3.5 mmol/L.
Patients with clinically relevant bradycardia (heart rate < 50 beats/min)
Patients with a complete left bundle branch block.
Patients with a history of uncontrolled or labile hypertension
Patients with a history of congestive heart failure.
Patients with a history of cardiomyopathy.
Patients with unstable angina pectoris.
Patients with a personal or family history of congenital or documented acquired QT interval prolongation.
Patients with a significant atrial or ventricular arrhythmia or symptomatic arrhythmia in the past.

Sites / Locations

Department of Dermatology - Universitäts-Hautklinik; Hauptstraße 7
Klinik für Dermatologie, Allergologie und Venerologie - Universitätsklinikum Schleswig-Holstein, Campus Lübeck; Ratzeburger Allee 160
Klinik für Dermatologie und Allergologie - Philips Universität; 35037
I Divisione di Dermatologia, Istituto Dermopatico dell'Immacolata, IRCCS;

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DF2156A 150 mg

Arm Description

150 mg capsule twice a day (every 12 h) for a maximum of 14 days

Outcomes

Primary Outcome Measures

Total number of blisters from baseline

Modified ABSIS score change from baseline

ABSIS score will be measured according to the pemphigus scoring sheet [Rosenbach, 2009] adjusted to the clinical manifestation in BP patients, as per specifications in protocol.

Physician Global Assessment (PGA) score measured on a 0-10 scale [Rosenbach, 2009]. Percent change from baseline

PGA score will be measured according to the following scale: 0 1 2 3 4 5 6 7 8 9 10 Perfect Worst health skin condition imaginable The following guidelines will help standardize PGA: 0: no lesions 2: almost cleared, no functional impairment 4: few lesions / low functional impairment 6: moderate 8: severe / extensive 10: life-threatening

Pruritus measured on a 10 cm visual analogue scale. Absolute value change from baseline

Pruritus will be measured according to the following scale: 0 10 No pruritus Worst pruritus I can imagine

Eosinophil blood count. Percent change from baseline

Percentage of patients with treatment failure (drug discontinuation due to disease worsening)

treatment failure (drug discontinuation due to disease worsening)

Percentage of patients completely free from blisters

Number of patients who are still free from blisters without requiring any systemic or topical rescue treatment - Optional

QTcF. Change from baseline

Incidence of Adverse Events and Serious Adverse Events

Blisters percent change from baseline

Modified ABSIS score percent change from baseline

ABSIS score will be measured according to the pemphigus scoring sheet [Rosenbach, 2009] adjusted to the clinical manifestation in BP patients, as per specifications in protocol.

Physician Global Assessment (PGA) score measured on a 0-10 scale [Rosenbach, 2009]. Absolute value change from baseline

Pruritus measured on a 10 cm visual analogue scale. Percent change from baseline

Pruritus will be measured according to the following scale: 0 10 No pruritus Worst pruritus I can imagine

Eosinophil blood count. Absolute number change from baseline

Number of patients with treatment failure (drug discontinuation due to disease worsening)

Number of patients with treatment failure (drug discontinuation due to diseas

Number of patients completely free from blisters

QTcF. Absolute value

Secondary Outcome Measures

Plasma levels of DF2156A and its major metabolites (DF2227 and DF2108) at steady state conditions

Full Information

NCT ID

NCT01571895

First Posted

April 4, 2012

Last Updated

September 26, 2022

Sponsor

Dompé Farmaceutici S.p.A

1. Study Identification

Unique Protocol Identification Number

NCT01571895

Brief Title

Pilot Efficacy and Safety Study of Oral DF2156A in Patients With Active Bullous Pemphigoid

Official Title

A Phase 2, Multicentre, Single Arm, Pilot Study to Assess the Efficacy and the Safety of 150 mg Twice a Day Oral DF2156A in Patients With Active Bullous Pemphigoid.

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Terminated

Why Stopped

Lack of efficacy observed at 1/3 of the enrollment at investigated dosage. No results available.

Study Start Date

February 20, 2012 (Actual)

Primary Completion Date

July 5, 2012 (Actual)

Study Completion Date

July 5, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Dompé Farmaceutici S.p.A

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The objective of this clinical trial was to evaluate whether DF2156A has a potential in improving the clinical outcome in patients with active blistering bullous pemphigoid (BP) to warrant its further development. The safety of DF2156A in the specific clinical setting was also evaluated.

Detailed Description

The study was a phase 2, multicentre, single arm, pilot study. It has been designed to determine if DF2156A has sufficient activity to warrant its further development. A total of twelve (12) BP patients were planned to be involved. They were planned to receive DF2156A orally at the dose of 150 mg twice a day for a maximum of 14 days. Recruitment was intended to be competitive among the study sites, until the planned number of patients is enrolled. Competitive recruitment has been chosen to increase the speed of recruitment and to account for any unexpected occurrence at a site that negatively impact enrolment rate. The single arm design has been chosen as an appropriate tool for this pilot phase 2 study, considering that BP is a rare disease where a placebo control is not acceptable. Moreover, as there is no spontaneous acute recovery from the active blistering condition, any improvement in patient outcome can be attributed to a positive effect of the Investigational Product. Each patient was intended to be involved in the study for a screening period, for 14 days of treatment, for all required measurements up to hospital discharge (planned on day 8+1 of treatment) and for one assessment occasion on day 15+1, either during hospital stay or after hospital discharge (out-patient visit). An optional post-treatment visit might be scheduled at day 30+3. Due to the lack of efficacy observed at 1/3 of the enrollment at the investigated dosage, the patients' enrollment was interrupted and trial, hence, was early terminated. More precisely, only 1 of the 4 enrolled patients completed the study's 14-day treatment period. The remaining 3 patients were discontinued from the study early (1 patient due to treatment failure and 2 patients who were discontinued and admitted to rescue therapy). While DF2156A appeared to be safe and was generally well-tolerated with only mild AEs reported in 3 patients (and no deaths, SAEs, or discontinuations from the study due to AEs), the limited sample size of the safety population prevents any overall conclusions of safety regarding the investigational product. For this reason no results other than listings are available. See the MEX0111 synopsis on the EU Clinical Trial Register: https://www.clinicaltrialsregister.eu/ctr-search/rest/download/result/attachment/2011-000756-42/1/27931

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Bullous Pemphigoid

Keywords

Autoimmune inflammatory blistering disorder

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

4 (Actual)

8. Arms, Groups, and Interventions

Arm Title

DF2156A 150 mg

Arm Type

Experimental

Arm Description

150 mg capsule twice a day (every 12 h) for a maximum of 14 days

Intervention Type

Drug

Intervention Name(s)

DF2156A

Intervention Description

DF2156A is a novel small molecule that inhibits the biological activity of the CXC ligand 8 [CXCL8; formerly interleukin (IL)-8] through inhibition of the activation of CXCL8 receptors: CXCR1 and CXCR2. This specific inhibitor stems from a program of drug design of molecules intended to modulate chemokine action.

Primary Outcome Measure Information:

Title

Total number of blisters from baseline

Description

Total number of blisters from baseline

Time Frame

day 0/1 (pre-dose), 8 and 15

Title

Modified ABSIS score change from baseline

Description

ABSIS score will be measured according to the pemphigus scoring sheet [Rosenbach, 2009] adjusted to the clinical manifestation in BP patients, as per specifications in protocol.

Time Frame

day 0/1 (pre-dose), 8 and 15

Title

Physician Global Assessment (PGA) score measured on a 0-10 scale [Rosenbach, 2009]. Percent change from baseline

Description

Time Frame

day 0/1 (pre-dose), 8 and 15

Title

Pruritus measured on a 10 cm visual analogue scale. Absolute value change from baseline

Description

Pruritus will be measured according to the following scale: 0 10 No pruritus Worst pruritus I can imagine

Time Frame

day 0/1 (pre-dose), 8 and 15

Title

Eosinophil blood count. Percent change from baseline

Description

Eosinophil blood count. Percent change from baseline

Time Frame

screening and day 15

Title

Percentage of patients with treatment failure (drug discontinuation due to disease worsening)

Description

treatment failure (drug discontinuation due to disease worsening)

Time Frame

day 8

Title

Percentage of patients completely free from blisters

Description

Percentage of patients completely free from blisters

Time Frame

day 15

Title

Number of patients who are still free from blisters without requiring any systemic or topical rescue treatment - Optional

Description

Number of patients who are still free from blisters without requiring any systemic or topical rescue treatment - Optional

Time Frame

Day 30

Title

QTcF. Change from baseline

Description

QTcF. Change from baseline

Time Frame

Italy: day 0/1 (pre-dose), day 1, 5, 8 and 15___Ger:day 0/1 (pre-dose), day 1, 3, 5, 8 and 15

Title

Incidence of Adverse Events and Serious Adverse Events

Description

Incidence of Adverse Events and Serious Adverse Events

Time Frame

throughout the study up to day 15 or 30

Title

Blisters percent change from baseline

Description

Blisters percent change from baseline

Time Frame

day 0/1 (pre-dose), 8 and 15

Title

Modified ABSIS score percent change from baseline

Description

ABSIS score will be measured according to the pemphigus scoring sheet [Rosenbach, 2009] adjusted to the clinical manifestation in BP patients, as per specifications in protocol.

Time Frame

day 0/1 (pre-dose), 8 and 15

Title

Physician Global Assessment (PGA) score measured on a 0-10 scale [Rosenbach, 2009]. Absolute value change from baseline

Description

Time Frame

day 0/1 (pre-dose), 8 and 15

Title

Pruritus measured on a 10 cm visual analogue scale. Percent change from baseline

Description

Pruritus will be measured according to the following scale: 0 10 No pruritus Worst pruritus I can imagine

Time Frame

day 0/1 (pre-dose), 8 and 15

Title

Eosinophil blood count. Absolute number change from baseline

Description

Eosinophil blood count. Absolute number change from baseline

Time Frame

screening and day 15

Title

Number of patients with treatment failure (drug discontinuation due to disease worsening)

Description

Number of patients with treatment failure (drug discontinuation due to diseas

Time Frame

day 8

Title

Number of patients completely free from blisters

Description

Number of patients completely free from blisters

Time Frame

day 15

Title

QTcF. Absolute value

Description

QTcF. Absolute value

Time Frame

Italy: day 0/1 (pre-dose), day 1, 5, 8 and 15___Ger:day 0/1 (pre-dose), day 1, 3, 5, 8 and 15

Secondary Outcome Measure Information:

Title

Plasma levels of DF2156A and its major metabolites (DF2227 and DF2108) at steady state conditions

Description

Plasma levels of DF2156A and its major metabolites (DF2227 and DF2108) at steady state conditions

Time Frame

day 5 and 8

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male and female patients aged >50 years. Patients with newly diagnosed or relapsing bullous pemphigoid based on clinical diagnosis to be confirmed by direct immunofluorescence and indirect immunofluorescence on salt-spit skin (or BP180 and/or BP230 ELISA). Confirmation by laboratory tests will be obtained ideally before or anyway within one week after enrolment. For the purpose of this study, clinical relapses are defined as re-appearance of clinical symptoms after the patient had attained remission lasting for more than 3 months without immunosuppressive treatment. In patients with relapsing BP, clinical diagnosis will be confirmed by indirect immunofluorescence or BP180 and/or BP230 ELISA only. Patients with mild to moderate active blistering disease (total number of blisters between 1 and 30) whether associated or not with urticarial/eczematous lesions. Patients with modified ABSIS score ≤50 Patients free from any systemic treatments that may affect the course of the disease with the following off-period prior to enrolment: 3 weeks: steroids, dapsone, tetracyclines, nicotinamide, 3 months: azathioprine, mycofenolate mofetil, cyclophosphamide, methotrexate, intravenous immunoglobulins, immunoadsorption, TNF antagonists 12 months: rituximab, leflunomide Patients free from any topical treatments other than topical antibiotics and antiseptics in the 4 days prior to enrolment. Patients able to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations. Patients able to provide informed consent. Exclusion Criteria: Patients with a Karnofsky rating score <40%. Patients with mucosal involvement. Patients with moderate to severe renal impairment as per calculated creatinine clearance (CLcr) < 50 mL/min according to the Cockcroft-Gault formula (Cockcroft-Gault , 1976). Patients with hepatic dysfunction defined by increased ALT/AST > 3 x upper limit of normal (ULN) and increased total bilirubin > 3 mg/dL [>51.3 μmol/L]. Patients with hypoalbuminemia defined as serum albumin < 3 g/dL. Patients with a baseline (day 0/1, pre-dose) QTcF > 470 msec. Patients who had a myocardial infarction in the 6 months prior to enrolment. Patients on treatment with phenytoin, warfarin, sulphonylurea hypoglycemics (e.g. tolbutamide, glipizide, glibenclamide/glyburide, glimepiride, nateglinide) and high dose of amitriptyline (> 50 mg/day). Patients with known hypersensitivity to non-steroidal antiinflammatory drugs. Patients using any investigational agent within 12 months prior to enrolment. Pregnant or breast feeding women. Unwillingness to use effective contraceptive measures up to 2 months after the end of study drug administration (females and males). Additional Exclusion Criteria for Germany only: Patients with hypokalemia defined as serum potassium < 3.5 mmol/L. Patients with clinically relevant bradycardia (heart rate < 50 beats/min) Patients with a complete left bundle branch block. Patients with a history of uncontrolled or labile hypertension Patients with a history of congestive heart failure. Patients with a history of cardiomyopathy. Patients with unstable angina pectoris. Patients with a personal or family history of congenital or documented acquired QT interval prolongation. Patients with a significant atrial or ventricular arrhythmia or symptomatic arrhythmia in the past.

Overall Study Officials: