Nomacopan Therapy in Adult Patients With Bullous Pemphigoid Receiving Adjunct Oral Corticosteroid Therapy (ARREST-BP)

Bullous Pemphigoid Clinical Trial

— ARREST-BP  

Official title:

A Randomized, Part A Partial Blinded and Part B Double Blinded, Placebo-controlled 24-week Clinical Study to Evaluate the Efficacy and Safety of Nomacopan Therapy in Adult Patients With Bullous Pemphigoid Receiving Adjunct Oral Corticosteroid Therapy (ARREST-BP)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05061771
• Other study ID #: AK802
• Status: Withdrawn
• Phase: Phase 3
• Start date: May 6, 2022
• Est. completion date: August 1, 2022

Study information

• Verified date: October 2022
• Source: AKARI Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A phase III two-part study of nomacopan, a bifunctional inhibitor of complement component C5 and leukotriene B4 (LTB4), for the treatment of moderate and severe bullous pemphigoid. There is evidence that both terminal complement activation (via C5) and the lipid mediator LTB4 may have a central role in driving the disease. In this study patients will be randomized to receive either nomacopan plus oral corticosteroids (OCS) or placebo plus OCS for a treatment period of 24 weeks. OCS will be tapered over the course of the treatment if the symptoms of disease improve.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 1, 2022
• Est. primary completion date: August 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

1. Male or female between 18 and 89 years of age inclusive at the time of consent with Karnofsky score of 50% or more at screening

2. Male or female =90 years of age at the time of consent with Karnofsky score of 70% or more at screening

3. Diagnosis of Bullous Pemphigoid either newly diagnosed or relapsing

4. Patients with confirmed atypical Bullous Pemphigoid

5. Bullous Pemphigoid classified as either moderate or severe on the basis of the Investigator Global Assessment (IGA) at randomisation

6. Willing to receive immunisation against Neisseria meningitidis and/or antibiotic prophylaxis

7. Provision of voluntary written informed consent

Exclusion Criteria:

1. Patients with recalcitrant BP that have never achieved CDA or who have never been in complete disease remission despite long term treatment with super potent topical steroid or oral cotricosteroid

2. Epidermolysis bullosa acquisita, mucous membrane pemphigoid, or anti p200 pemphigoid

3. Mucosal lesions BPDAI score accounts for =30% of total BPDAI activity score at randomisation

4. BP considered to be drug induced, in particular diagnosis of BP made within two months of starting a drug well known to induce BP

5. Treatment with BP-directed biologics including: a) Any cell-depleting agents including, but not limited to, rituximab within 12 months prior to baseline, b) Other biologics within five half-lives (if known) or 16 weeks prior to the baseline, whichever is longer, or c) Intravenous immunoglobulin within 16 weeks prior to the baseline.

6. Taking > 0.3 mg/kg/day OCS at screening

7. Treatment with systemic immunomodulators such as dapsone or doxycycline within four half-lives of the drugs prior to baseline Day 1

8. Treatment with immunosuppressants within the last two weeks prior to baseline

9. Treatment with an anti-complement therapy or with Zileuton within the last three months prior to baseline

10. OCS dose no more than 0.3mg/kg/day in the 7 days before screening visit

11. Taking super-potent topical corticosteroids and unable to discontinue them at or before the screening assessment

12. Active systemic or organ system bacterial or fungal infection or progressive severe infection

13. Known congenital immunodeficiency or a history of acquired immunodeficiency including a positive human immunodeficiency virus (HIV) test

14. Active infection with hepatitis B or C

15. Positive nasal throat swab for Neisseria species

16. Known hypersensitivity to nomacopan and any of its excipients

17. Receipt of live attenuated vaccines within 2 weeks of Day 1

Related Conditions & MeSH terms

• Bullous Pemphigoid
• Pemphigoid, Bullous

Intervention

Drug:
• nomacopan (rVA576)
Nomacopan an inhibitor of complement C5 and LTB4

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
Germany	MENSINGDERMA Research GmbH	Hamburg
Germany	Universitätsklinikum Schleswig-Holstein	Kiel
Germany	Universitäts Hautklinik	Tübingen
Netherlands	University Medical Center Groningen	Groningen
Poland	Cityclinic Przychodnia Lekarsko-Psychologiczna Matusiak Spólka Partnerska	Wroclaw
United States	David Fivenson MD PLC	Ann Arbor	Michigan
United States	Duke Dermatology	Durham	North Carolina
United States	Wright State Physicians 725 University Blvd.	Fairborn	Ohio
United States	Dawes Fretzin Clinical Research Group LLC	Indianapolis	Indiana
United States	Tulane University Health Sciences Center	Los Angeles	California
United States	UMPC Department of Dermatology	Pittsburgh	Pennsylvania
United States	North Shore University Health System	Skokie	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
AKARI Therapeutics

Countries where clinical trial is conducted

United States,  Germany,  Netherlands,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Achievement of Complete Disease Remission	Proportion of patients in Complete Disease Remission	weeks 16 - 24
Secondary	Cumulative oral corticosteroid, OCS, during treatment	Cumulative OCS used during treatment	Randomization to 24 weeks
Secondary	Proportion of patients requiring rescue therapy	Proportion of patients requiring rescue therapy during the 24 weeks of treatment	Randomization to 24 weeks
Secondary	Achievement Partial Disease Remission	Proportion of patients in Partial Disease Remission	weeks 16 - 24
Secondary	Time to onset of Complete Disease Remission	Time (weeks) to onset of Complete Disease Remission	week 6 to 24
Secondary	Duration of Complete and Partial Disease Remission	Duration (weeks) of Complete Disease Remission and Partial Disease Remission	week 6 to 24
Secondary	Investigator Global Assessment (IGA) score	Proportion of patients with Investigator Global Assessment (IGA) score of 0 or 1	weeks 6 - 24
Secondary	Adverse Events	Frequency, type and relationship of AEs to treatment	Day 1 to Week 28
Secondary	Steroid-related AEs	Incidence of steroid-related AEs	Day 1 to Week 28
Secondary	Dermatology Life Quality Index (DLQI)	Change from baseline in Dermatology Life Quality Index (DLQI)	Randomisation to week 24
Secondary	Incidence of treatment-emergent anti-drug antibody (ADA) responses and titre and neutralising potential assessed in vitro at baseline and every 4 weeks	Incidence of treatment-emergent anti-drug antibody (ADA) responses and titre and neutralising potential assessed in vitro at baseline and then every 4 weeks	Day 1 to Week 28