Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00004194

Trial Description

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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.

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

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.

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Brief Summary in Scientific Language

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Organizational Data

  •   DRKS00004194
  •   2013/08/06
  •   2012/04/04
  •   no
  •   [---]*
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Secondary IDs

  •   2011-000756-42 
  •   NCT01571895  (ClinicalTrials.gov)
  •   AIFA Codice: 10006567 
  •   MEX0111  (Dompé s.p.a.)
  •   2011-000756-42 
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Health Condition or Problem studied

  •   Bullous Pemphigoid
  •   L12.0 -  Bullous pemphigoid
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Interventions/Observational Groups

  •   Drug: DF2156A
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   II
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Primary Outcome

- Total number of blisters from baseline; time frame: day 0/1 (pre-dose), 8 and 15; Total number of blisters from baseline
- Modified ABSIS score change from baseline; time frame: day 0/1 (pre-dose), 8 and 15; 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; 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; 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
- Percentage of patients with treatment failure (drug discontinuation due to disease worsening); time frame: day 8
- Percentage of patients completely free from blisters; time frame: day 15
- Number of patients who are still free from blisters without requiring any systemic or topical rescue treatment - Optional; time frame: Day 30
- 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)
- Routine laboratory tests (haematology, clinical chemistry); time frame: screening and day 15 (or withdrawal)
- 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
- Incidence of Adverse Events and Serious Adverse Events; time frame: throughout the study up to day 15 or 30
- Blisters percent change from baseline; time frame: day 0/1 (pre-dose), 8 and 15; Blisters percent change from baseline
- Modified ABSIS score percent change from baseline; time frame: day 0/1 (pre-dose), 8 and 15; 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; 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; 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
- Number of patients with treatment failure (drug discontinuation due to disease worsening); time frame: day 8
- Number of patients completely free from blisters; time frame: day 15
- 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

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Secondary Outcome

- Plasma levels of DF2156A and its major metabolites (DF2227 and DF2108) at steady state conditions; time frame: day 5 and 8

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Countries of Recruitment

  •   Germany
  •   Italy
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Locations of Recruitment

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Recruitment

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  •   2011/07/31
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  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional 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.

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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 ╬╝mol/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.

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Addresses

  • start of 1:1-Block address primary-sponsor
    • Dompé s.p.a.
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    • I Divisione di Dermatologia, Istituto Dermopatico dell'Immacolata, IRCCS; Via Monti di Creta 104 - 00167 Roma, Italy
    • Biagio Didona, MD 
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    • I Divisione di Dermatologia, Istituto Dermopatico dell'Immacolata, IRCCS; Via Monti di Creta 104 - 00167 Roma, Italy
    • Biagio Didona, MD 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting stopped after recruiting started
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   2
  •   2014/11/27
* This entry means the parameter is not applicable or has not been set.