Clinical trial NCT05061771: Nomacopan Therapy in Adult Patients With Bullous Pemphigoid Receiving Adjunct Oral Corticosteroid Therapy (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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Bullous Pemphigoid
Keywords: pemphigoid
blistering skin disease
nomacopan
complement
leukotriene
Lead sponsor: AKARI Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-09-30
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Achievement of Complete Disease Remission
timeFrame: weeks 16 - 24
Secondary outcomes:
measure: Cumulative oral corticosteroid, OCS, during treatment
timeFrame: Randomization to 24 weeks
measure: Proportion of patients requiring rescue therapy
timeFrame: Randomization to 24 weeks
measure: Achievement Partial Disease Remission
timeFrame: weeks 16 - 24
measure: Time to onset of Complete Disease Remission
timeFrame: week 6 to 24
measure: Duration of Complete and Partial Disease Remission
timeFrame: week 6 to 24
measure: Investigator Global Assessment (IGA) score
timeFrame: weeks 6 - 24
measure: Adverse Events
timeFrame: Day 1 to Week 28
measure: Steroid-related AEs
timeFrame: Day 1 to Week 28
measure: Dermatology Life Quality Index (DLQI)
timeFrame: Randomisation to week 24
measure: Incidence of treatment-emergent anti-drug antibody (ADA) responses and titre and neutralising potential assessed in vitro at baseline and every 4 weeks
timeFrame: Day 1 to Week 28
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Tulane University Health Sciences Center
state: California
city: Skokie
country: United States
facility: North Shore University Health System
state: Illinois
city: Indianapolis
country: United States
facility: Dawes Fretzin Clinical Research Group LLC
state: Indiana
city: Ann Arbor
country: United States
facility: David Fivenson MD PLC
state: Michigan
city: Durham
country: United States
facility: Duke Dermatology
state: North Carolina
city: Fairborn
country: United States
facility: Wright State Physicians 725 University Blvd.
state: Ohio
city: Pittsburgh
country: United States
facility: UMPC Department of Dermatology
state: Pennsylvania
city: Hamburg
country: Germany
facility: MENSINGDERMA Research GmbH
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Tübingen
country: Germany
facility: Universitäts Hautklinik
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Wrocław
country: Poland
facility: Cityclinic Przychodnia Lekarsko-Psychologiczna Matusiak Spółka Partnerska
Study officials:
References: