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

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)

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.

Study Overview

• Status: Withdrawn
• Conditions: Bullous Pemphigoid
• Intervention / Treatment: Other: Placebo; Drug: nomacopan (rVA576)

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Hamburg, Germany, 22391
    • MensingDerma research GmbH
  • Kiel, Germany, 24105
    • Universitatsklinikum Schleswig-Holstein
  • Tübingen, Germany, 72076
    • Universitäts Hautklinik
• Netherlands
  • Groningen, Netherlands, 9700RB
    • University Medical Center Groningen
• Poland
  • Wrocław, Poland
    • Cityclinic Przychodnia Lekarsko-Psychologiczna Matusiak Spółka Partnerska
• United States
  • California
    • Los Angeles, California, United States, 70112
      • Tulane University Health Sciences Center
  • Illinois
    • Skokie, Illinois, United States, 60077
      • North Shore University Health System
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Dawes Fretzin Clinical Research Group LLC
  • Michigan
    • Ann Arbor, Michigan, United States, 48103
      • David Fivenson MD PLC
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Dermatology
  • Ohio
    • Fairborn, Ohio, United States, 45324
      • Wright State Physicians 725 University Blvd.
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UMPC Department of Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: nomacopan (rVA576); PART A: High dose nomacopan (standard complement ablating doses on Day 1 followed by 45 mg qd) administered by subcutaneous injection, plus a starting dose of 0.5 mg/kg/day OCS qd or Low dose nomacopan (standard complement ablating doses on Day 1 followed by 15 mg qd) administered by subcutaneous injection, plus a starting dose of 0.5 mg/kg/day OCS PART B: Nomacopan (standard complement ablating doses on Day 1 followed by to be confirmed mg qd) administered by subcutaneous injection, plus a starting dose of 0.5 mg/kg/day OCS qd	Drug: nomacopan (rVA576); Nomacopan an inhibitor of complement C5 and LTB4
Placebo Comparator: Placebo; PART A: Placebo (matching standard complement ablating doses on Day 1 and then matching injection volume of 45mg dose qd) administered by subcutaneous injection, plus a starting dose of 0.5 mg/kg/day oral corticosteroid (OCS) qd or Placebo (matching standard complement ablating doses on Day 1 and then matching injection volume of 15mg dose qd) administered by subcutaneous injection, plus a starting dose of 0.5 mg/kg/day oral corticosteroid (OCS) qd PART B: Placebo (matching standard complement ablating doses on Day 1 and then matching injection volume of active dose qd) administered by subcutaneous injection, plus a starting dose of 0.5 mg/kg/day oral corticosteroid (OCS) qd	Other: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of Complete Disease Remission	Proportion of patients in Complete Disease Remission	weeks 16 - 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative oral corticosteroid, OCS, during treatment	Cumulative OCS used during treatment	Randomization to 24 weeks
Proportion of patients requiring rescue therapy	Proportion of patients requiring rescue therapy during the 24 weeks of treatment	Randomization to 24 weeks
Achievement Partial Disease Remission	Proportion of patients in Partial Disease Remission	weeks 16 - 24
Time to onset of Complete Disease Remission	Time (weeks) to onset of Complete Disease Remission	week 6 to 24
Duration of Complete and Partial Disease Remission	Duration (weeks) of Complete Disease Remission and Partial Disease Remission	week 6 to 24
Investigator Global Assessment (IGA) score	Proportion of patients with Investigator Global Assessment (IGA) score of 0 or 1	weeks 6 - 24
Adverse Events	Frequency, type and relationship of AEs to treatment	Day 1 to Week 28
Steroid-related AEs	Incidence of steroid-related AEs	Day 1 to Week 28
Dermatology Life Quality Index (DLQI)	Change from baseline in Dermatology Life Quality Index (DLQI)	Randomisation to week 24
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

Collaborators and Investigators

• Sponsor: AKARI Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2022
• Primary Completion (Actual): August 1, 2022
• Study Completion (Actual): August 1, 2022

Study Registration Dates

• First Submitted: September 15, 2021
• First Submitted That Met QC Criteria: September 27, 2021
• First Posted (Actual): September 30, 2021

Study Record Updates

• Last Update Posted (Actual): April 9, 2025
• Last Update Submitted That Met QC Criteria: April 8, 2025
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: pemphigoid; blistering skin disease; nomacopan; complement; leukotriene
• Additional Relevant MeSH Terms: Autoimmune Diseases; Immune System Diseases; Skin Diseases; Skin Diseases, Vesiculobullous; Pemphigoid, Bullous
• Other Study ID Numbers: AK802

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No