A Study of PRN1008 in Adult Patients With Pemphigus Vulgaris

Study Description

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Brief Summary:

Open-label cohort study in adult patients with newly diagnosed or relapsing pemphigus vulgaris, with intra-patient dose-adjustment based on clinical response and BTK occupancy, and with conventional immunosuppressive "rescue treatment", if indicated. The duration of therapy will be 12 weeks, followed by 12 weeks of follow up.

Condition or disease	Intervention/treatment	Phase
Pemphigus Vulgaris	Drug: PRN1008	Phase 2

Detailed Description:

Primary Objectives:

To evaluate the safety of PRN1008 in patients with pemphigus vulgaris (PV) To evaluate the clinical activity of PRN1008 in patients with PV, per criteria in the European Academy of Dermatology and Venereology (EADV) 2014 Pemphigus S2 Guideline (Hertl et al. 2015)

Secondary Objectives To evaluate the pharmacokinetics (PK) and the pharmacodynamics (PD) of multiple doses of PRN1008 in patients with PV To evaluate the relationship of PK and PD to each other and to efficacy and safety in this patient population

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	25 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Masking Description:	Open Label
Primary Purpose:	Treatment
Official Title:	An Open-Label, Phase 2, Pilot Study Investigating the Safety, Clinical Activity, Pharmacokinetics, and Pharmacodynamics of Oral Treatment With the BTK Inhibitor PRN1008 in Patients With Newly Diagnosed or Relapsing Pemphigus Vulgaris
Study Start Date :	February 2016
Estimated Primary Completion Date :	December 2019
Estimated Study Completion Date :	December 2019

Arms and Interventions

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Arm	Intervention/treatment
Experimental: PRN1008; Open-label PRN1008, 12 weeks; 12 week follow up	Drug: PRN1008; PRN1008, oral dose, 12 weeks; Other Name: BTK inhibitor

Outcome Measures

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Primary Outcome Measures :

1. Incidence of treatment-emergent adverse events at 12 weeks [ Time Frame: 12 weeks treatment ]
   The incidence of treatment-emergent adverse events (TEAEs), including clinically significant changes in physical examination, laboratory tests, and vital signs.
2. Control of disease activity at 4 weeks [ Time Frame: 4 weeks treatment ]
   The proportion of subjects who are able to achieve control of disease activity (CDA) within 4 weeks of starting PRN1008 treatment without the need for doses of prednisone or prednisolone >0.5 mg/kg.

Secondary Outcome Measures :

1. Time to control of disease activity (CDA) [ Time Frame: 12 week treatment; 12 week follow up ]
   Time to control of disease activity (CDA) as defined in European Academy of Dermatology and Venereology (EADV) 2015 Pemphigus S2 Guideline
2. Time to end of consolidation phase [ Time Frame: 12 week treatment; 12 week follow up ]
   Time to end of consolidation phase as defined in European Academy of Dermatology and Venereology (EADV) 2015 Pemphigus S2 Guideline
3. Time to complete remission [ Time Frame: 12 week treatment; 12 week follow up ]
   Time to complete remission as defined in European Academy of Dermatology2015 Pemphigus S2 Guideline
4. Time to relapse after PRN1008 treatment discontinuation [ Time Frame: 12 week treatment; 12 week follow up ]
   Time to relapse after PRN1008 treatment discontinuation as defined in European Academy of Dermatology and Venereology (EADV) 2015 Pemphigus S2 Guideline

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Male or female patients, aged 18 to 80 years old, with biopsy-proven, mild-moderate PV (PDAI 8 to 45) that are either:

  • newly diagnosed patients (i.e. naïve to an effective induction treatment regimen) for whom an initial period of PRN1008 monotherapy is judged clinically acceptable, or
  • relapsing patients, for whom an initial period of PRN1008 monotherapy, or combination therapy with any of low dose corticosteroid (≤ 10 mg/day), azathioprine, mycophenolate mofetil, sulfasalazine and dapsone, is judged clinically acceptable, provided cessation of azathioprine, mycophenolate mofetil, sulfasalazine, and dapsone within two to four weeks is anticipated

Exclusion Criteria:

• Pregnant or lactating women
• A history of malignancy of any type, other than surgically excised non-melanoma skin cancers or in situ cervical cancer within 5 years before the day of dosing
• Use of immunologic response modifiers with the following periods prior to Day 1: 1 week: cyclophosphamide; 4 weeks: Kinaret (anakinra) and Enbrel (etanercept); 12 weeks: Remicade (infliximab), Humira (adalimumab), Simponi (golimumab), Orencia (abatacept), Actemra (tocilizumab), Cimzia (certolizumab), Cosentyx (secukinumab), intravenous immunoglobulin, plasmapheresis; 6 months: Rituxan/MabThera (rituximab), ofatumumab, any other anti-CD20 antibody
• Use of >10 mg per day of oral prednisolone for more than 1 week within 4 weeks prior to Day 1 (inhaled and mucosal [for symptomatic treatment of oral lesions] corticosteroids are allowed)
• Has received any investigational drug (or is currently using an investigational device) within the 30 days before receiving the first dose of study medication, or at least 5 times the respective elimination half-life time (whichever is longer)
• Donation of a unit or more of blood or blood products within 4 weeks prior to Day 1
• History of solid organ transplant
• Positive for screening for HIV, hepatitis B (surface and core antibodies unrelated to vaccination), or hepatitis C (anti-HCV antibody confirmed with Hep C RNA)
• History of active or latent tuberculosis (TB) infection (subjects must also test negative using the QuantiFERON® test to be eligible for the study)

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Steven G Gourlay, MBBS PhD	650-416-7700
Contact: Robert C Quesenberry, BS PMP CRP	650-416-7700

Locations

Australia, New South Wales
Premier Specialists	Recruiting
Kogarah, New South Wales, Australia, 2217
Contact: Charmaine Peras, RN +61295985800 murrell.patients@ori.org.au
Principal Investigator: Dedee F. Murrell, BMBCh FRCP
Australia, Victoria
Sinclair Dermatology	Recruiting
East Melbourne, Victoria, Australia, 3002
Contact: Carol Robinson +61 3 9654 2426 Carol.Robinson@sinclairdermatology.com.au
Principal Investigator: Rodney D Sinclair, MBBS MD FACD
Royal Melbourne, Dermatology Office	Recruiting
Melbourne, Victoria, Australia, 3050
Contact: Annette Phemister, RN +61 3 9342 4531 Annette.phemister@mh.org.au
Principal Investigator: George A Varigos, MBBS PhD
Croatia
Clinical Hospital Osijek	Recruiting
Osijek, Croatia, 31000
Contact: Jasmina Knezevic +385915460138 knezevic.jasmina@kbo.hr
Principal Investigator: Marija Sola, MD
Klinichki Bolnicki Centar Zagreb	Recruiting
Zagreb, Croatia, 10 000
Contact: Tanja Vrcic, MD +38516051935 tanja.vrcic@gmail.com
Principal Investigator: Branka Marinovic, MD, PhD
France
Hôpital Avicenne	Recruiting
Bobigny, Siene-Saint Denis, France, 93009
Contact: Frederic Caux +33148955189
Principal Investigator: Frederic Caux
Rouen University Hospital	Recruiting
Rouen, France, 76038
Contact: Samir Stiti +33243434351 samir.stiti@chu-rouen.fr
Principal Investigator: Pascal Joly, MD
Greece
University General Hospital of Ioannina	Recruiting
Ioánnina, Ioannina, Greece, 45500
Contact: Chrisanthi Tziortzioti +306949082918 sissitziortzioti@gmail.com
Contact: George Gaitanis +306974508561 ggaitan@cc.uoi.gr
Principal Investigator: Ioannis Bassukas, MD
University Hospital of Larissa	Recruiting
Larissa, Thessaly, Greece, 41110
Contact: Angeliki-Viktoria Roussaki-Schulze, MD roussaki@otenet.gr
Principal Investigator: Angeliki-Viktoria Roussaki-Schulze, MD
Hospital of Venereal and Skin Diseases A.Syggros	Recruiting
Athens, Greece, 16121
Contact: Ioanna Kalkounou +306945860027 ikalkounou@yahoo.gr
Principal Investigator: Panagiotis Stavropoulos, MD
Papageorgiou General Hospital of Thessaloniki	Recruiting
Thessaloniki, Greece, 56429
Contact: Aikaterini Kyriakou +302313323291 docmouli@gmail.com
Principal Investigator: Aikaterini Patsatsi, MD
Israel
Chaim Sheba Medical Center	Recruiting
Ramat-Gan, Israel, 52621
Contact: Yaron Ben-Mordechai +97236666666 jaronbm@gmail.com
Principal Investigator: Sharon Baum, MD
Tel Aviv Sourasky Medical Center	Recruiting
Tel Aviv, Israel, 64239
Contact: Dvora Cohen +97236973768 dvoray@tlvmc.gov.il
Principal Investigator: Tal Zeeli, MD

Sponsors and Collaborators

Principia Biopharma, Inc.

Principia Biopharma Australia Pty Ltd.

Investigators

Study Director:	Steven G Gourlay, MBBS, PhD	Principia Biopharma

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Principia Biopharma, Inc.
ClinicalTrials.gov Identifier:	NCT02704429 History of Changes
Other Study ID Numbers:	PRN1008-005
First Posted:	March 10, 2016
Last Update Posted:	December 7, 2017
Last Verified:	December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Additional relevant MeSH terms:

Pemphigus; Skin Diseases, Vesiculobullous; Skin Diseases; Autoimmune Diseases; Immune System Diseases