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

This study has been terminated.
(Limited efficacy response observed at 1/3 enrollment at investigated dosage.)
Sponsor:
Information provided by (Responsible Party):
Dompé s.p.a.
ClinicalTrials.gov Identifier:
NCT01571895
First received: April 4, 2012
Last updated: June 25, 2014
Last verified: June 2014
  Purpose

The study will be 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 will be involved, who will be administered DF2156A orally at the dose of 150 mg twice a day for a maximum of 14 days.

Recruitment will 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 will 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.

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


Condition Intervention Phase
Bullous Pemphigoid
Drug: DF2156A
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Dompé s.p.a.:

Primary Outcome Measures:
  • Total number of blisters from baseline [ Time Frame: day 0/1 (pre-dose), 8 and 15 ] [ Designated as safety issue: No ]
    Total number of blisters from baseline

  • Modified ABSIS score change from baseline [ Time Frame: day 0/1 (pre-dose), 8 and 15 ] [ Designated as safety issue: No ]
    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 [ Time Frame: day 0/1 (pre-dose), 8 and 15 ] [ Designated as safety issue: No ]

    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 [ Time Frame: day 0/1 (pre-dose), 8 and 15 ] [ Designated as safety issue: No ]

    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 [ Time Frame: screening and day 15 ] [ Designated as safety issue: No ]
  • Percentage of patients with treatment failure (drug discontinuation due to disease worsening) [ Time Frame: day 8 ] [ Designated as safety issue: No ]
  • Percentage of patients completely free from blisters [ Time Frame: day 15 ] [ Designated as safety issue: No ]
  • Number of patients who are still free from blisters without requiring any systemic or topical rescue treatment - Optional [ Time Frame: Day 30 ] [ Designated as safety issue: No ]
  • Vital signs (blood pressure and heart rate) [ Time Frame: Italy: screening and day 15 (or withdrawal)___Ger: screening, day 1, 3, 5 and day 15 (or withdrawal) ] [ Designated as safety issue: Yes ]
  • Routine laboratory tests (haematology, clinical chemistry) [ Time Frame: screening and day 15 (or withdrawal) ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Incidence of Adverse Events and Serious Adverse Events [ Time Frame: throughout the study up to day 15 or 30 ] [ Designated as safety issue: Yes ]
  • Blisters percent change from baseline [ Time Frame: day 0/1 (pre-dose), 8 and 15 ] [ Designated as safety issue: No ]
    Blisters percent change from baseline

  • Modified ABSIS score percent change from baseline [ Time Frame: day 0/1 (pre-dose), 8 and 15 ] [ Designated as safety issue: No ]
    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 [ Time Frame: day 0/1 (pre-dose), 8 and 15 ] [ Designated as safety issue: No ]

    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. Percent change from baseline [ Time Frame: day 0/1 (pre-dose), 8 and 15 ] [ Designated as safety issue: No ]

    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 [ Time Frame: screening and day 15 ] [ Designated as safety issue: No ]
  • Number of patients with treatment failure (drug discontinuation due to disease worsening) [ Time Frame: day 8 ] [ Designated as safety issue: No ]
  • Number of patients completely free from blisters [ Time Frame: day 15 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Plasma levels of DF2156A and its major metabolites (DF2227 and DF2108) at steady state conditions [ Time Frame: day 5 and 8 ] [ Designated as safety issue: No ]

Enrollment: 4
Study Start Date: July 2011
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DF 2156A 150 mg
150 mg capsule twice a day (every 12 h) for a maximum of 14 days
Drug: DF2156A
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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:

    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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01571895

Locations
Germany
Department of Dermatology - Universitäts-Hautklinik; Hauptstraße 7
Freiburg, Germany, 79104
Klinik für Dermatologie, Allergologie und Venerologie - Universitätsklinikum Schleswig-Holstein, Campus Lübeck; Ratzeburger Allee 160
Lübeck, Germany, 23538
Klinik für Dermatologie und Allergologie - Philips Universität; Baldingersstraße - 35037
Marburg, Germany, 35037
Italy
I Divisione di Dermatologia, Istituto Dermopatico dell'Immacolata, IRCCS; Via Monti di Creta 104
Roma, Italy, 00167
Sponsors and Collaborators
Dompé s.p.a.
Investigators
Principal Investigator: Biagio Didona, MD I Divisione di Dermatologia, Istituto Dermopatico dell'Immacolata, IRCCS; Via Monti di Creta 104 - 00167 Roma, Italy
Principal Investigator: Detlef Zillikens, MD Klinik für Dermatologie, Allergologie und Venerologie - Universitätsklinikum Schleswig-Holstein, Campus Lübeck; Ratzeburger Allee 160 - 23538 Lübeck, Germany
Principal Investigator: Andrea Kneisel, MD Klinik für Dermatologie und Allergologie - Philips Universität; Baldingersstraße - 35037 Marburg, Germany
Principal Investigator: Johannes Kern, MD Department of Dermatology - Universitäts-Hautklinik; Hauptstraße 7 - 79104 Freiburg, Germany
Study Director: Pier Adelchi Ruffini, MD Development Director Dompé s.p.a. - Milan Offices - Via S. Martino 12-12/A, 20122 - Italy
  More Information

No publications provided

Responsible Party: Dompé s.p.a.
ClinicalTrials.gov Identifier: NCT01571895     History of Changes
Other Study ID Numbers: MEX0111, 2011-000756-42
Study First Received: April 4, 2012
Last Updated: June 25, 2014
Health Authority: Italy: The Italian Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Dompé s.p.a.:
Autoimmune inflammatory blistering disorder

Additional relevant MeSH terms:
Pemphigoid, Bullous
Skin Diseases, Vesiculobullous
Skin Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on August 25, 2014