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

Phase 3

Withdrawn

• Conditions: Bullous Pemphigoid
• Interventions: Drug: nomacopan (rVA576); Other: Placebo

• Registration Number: NCT05061771
• Lead Sponsor: AKARI Therapeutics

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-09-15
• Study First Submitted QC: 2021-09-27
• Study First Posted: 2021-09-30
• Study Start: 2022-05-06
• Primary Completion: 2022-08-01
• Study Completion: 2022-08-01
• Status Verified: 2022-10
• Last Update Submitted: 2024-02-07
• Last Update Posted: 2024-02-08

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
nomacopan (rVA576)	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
Placebo	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

Primary Outcome Measures

Name	Time	Method
Achievement of Complete Disease Remission	weeks 16 - 24	Proportion of patients in Complete Disease Remission

Secondary Outcome Measures

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

Trial Locations

Locations (12)

Tulane University Health Sciences Center; 🇺🇸 Los Angeles, California, United States

North Shore University Health System; 🇺🇸 Skokie, Illinois, United States

Dawes Fretzin Clinical Research Group LLC; 🇺🇸 Indianapolis, Indiana, United States

MENSINGDERMA Research GmbH; 🇩🇪 Hamburg, Germany

Wright State Physicians 725 University Blvd.; 🇺🇸 Fairborn, Ohio, United States

UMPC Department of Dermatology; 🇺🇸 Pittsburgh, Pennsylvania, United States

Universitätsklinikum Schleswig-Holstein; 🇩🇪 Kiel, Germany

Universitäts Hautklinik; 🇩🇪 Tübingen, Germany

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands

Cityclinic Przychodnia Lekarsko-Psychologiczna Matusiak Spółka Partnerska; 🇵🇱 Wrocław, Poland

David Fivenson MD PLC; 🇺🇸 Ann Arbor, Michigan, United States

Duke Dermatology; 🇺🇸 Durham, North Carolina, United States