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

NCT01571895 | Terminated Phase 2 DMC

• 2 other identifiers: MEX01112011-000756-42
• Study Type: interventional
• Target: 4
• Locations: 2 countries
• Sites: 4

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.

Conditions

Bullous Pemphigoid

Keywords

Autoimmune inflammatory blistering disorder

Outcome Measures

Primary Outcomes (18)

• Total number of blisters from baseline

  Total number of blisters from baseline

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

• 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.

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

• 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

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

• 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

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

• Eosinophil blood count. Percent change from baseline

  Eosinophil blood count. Percent change from baseline

  screening and day 15

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

  treatment failure (drug discontinuation due to disease worsening)

  day 8

• Percentage of patients completely free from blisters

  Percentage of patients completely free from blisters

  day 15

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

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

  Day 30

• QTcF. Change from baseline

  QTcF. Change from baseline

  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

  Incidence of Adverse Events and Serious Adverse Events

  throughout the study up to day 15 or 30

• Blisters percent change from baseline

  Blisters percent change from baseline

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

• 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.

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

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

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

• 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

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

• Eosinophil blood count. Absolute number change from baseline

  Eosinophil blood count. Absolute number change from baseline

  screening and day 15

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

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

  day 8

• Number of patients completely free from blisters

  Number of patients completely free from blisters

  day 15

• QTcF. Absolute value

  QTcF. Absolute value

  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 Outcomes (1)

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

  day 5 and 8

Study Arms (1)

DF2156A 150 mg

EXPERIMENTAL

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

Drug: DF2156A

Interventions

DF2156A DRUG

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.

DF2156A 150 mg

Eligibility Criteria

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

You may qualify if:

• 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:
• weeks: steroids, dapsone, tetracyclines, nicotinamide,
• months: azathioprine, mycofenolate mofetil, cyclophosphamide, methotrexate, intravenous immunoglobulins, immunoadsorption, TNF antagonists
• 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.

You may not qualify if:

• 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).
• 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

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead

Study Sites (4)

Department of Dermatology - Universitäts-Hautklinik; Hauptstraße 7

Freiburg im Breisgau, 79104, Germany

Location

Klinik für Dermatologie, Allergologie und Venerologie - Universitätsklinikum Schleswig-Holstein, Campus Lübeck; Ratzeburger Allee 160

Lübeck, 23538, Germany

Location

Klinik für Dermatologie und Allergologie - Philips Universität; 35037

Marburg, 35037, Germany

Location

I Divisione di Dermatologia, Istituto Dermopatico dell'Immacolata, IRCCS;

Roma, 00167, Italy

Location

MeSH Terms

Conditions

Pemphigoid, Bullous

Interventions

2'-((4'-trifluoromethanesulfonyloxy)phenyl)-N-methanesulfonylpropionamide

Condition Hierarchy (Ancestors)

Skin Diseases, Vesiculobullous; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Biagio Didona, MD

  I Divisione di Dermatologia, Istituto Dermopatico dell'Immacolata, IRCCS; 00167 Roma, Italy

  PRINCIPAL INVESTIGATOR

• Detlef Zillikens, MD

  Klinik für Dermatologie, Allergologie und Venerologie - Univ. Schleswig-Holstein; Lübeck, Germany

  PRINCIPAL INVESTIGATOR

• Andrea Kneisel, MD

  Klinik für Dermatologie und Allergologie - Philips Universität; 35037 Marburg, Germany

  PRINCIPAL INVESTIGATOR

• Johannes Kern, MD

  Department of Dermatology - Universitäts-Hautklinik; 79104 Freiburg, Germany

  PRINCIPAL INVESTIGATOR

• Pier Adelchi Ruffini, MD

  Development Director Dompé s.p.a., 20122 Milan, Italy

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2012
• First Posted: April 5, 2012
• Study Start: February 20, 2012
• Primary Completion: July 5, 2012
• Study Completion: July 5, 2012
• Last Updated: December 22, 2023

Record last verified: 2023-12

Locations

DE (3); IT (1)