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

• ClinicalTrials.gov Identifier: NCT05061771
• Recruitment Status: Withdrawn
• First Posted: September 30, 2021
• Last Update Posted: February 8, 2024
• Sponsor: AKARI Therapeutics
• Information provided by (Responsible Party): AKARI Therapeutics

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Bullous Pemphigoid	Drug: nomacopan (rVA576); Other: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: May 6, 2022
• Actual Primary Completion Date: August 1, 2022
• Actual Study Completion Date: August 1, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Achievement of Complete Disease Remission [ Time Frame: weeks 16 - 24 ]
   Proportion of patients in Complete Disease Remission

Secondary Outcome Measures :

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

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, California

Tulane University Health Sciences Center

Los Angeles, California, United States, 70112

United States, Illinois

North Shore University Health System

Skokie, Illinois, United States, 60077

United States, Indiana

Dawes Fretzin Clinical Research Group LLC

Indianapolis, Indiana, United States, 46250

United States, Michigan

David Fivenson MD PLC

Ann Arbor, Michigan, United States, 48103

United States, North Carolina

Duke Dermatology

Durham, North Carolina, United States, 27710

United States, Ohio

Wright State Physicians 725 University Blvd.

Fairborn, Ohio, United States, 45324

United States, Pennsylvania

UMPC Department of Dermatology

Pittsburgh, Pennsylvania, United States, 15213

Germany

MENSINGDERMA Research GmbH

Hamburg, Germany, 22391

Universitätsklinikum Schleswig-Holstein

Kiel, Germany, 24105

Universitäts Hautklinik

Tübingen, Germany, 72076

Netherlands

University Medical Center Groningen

Groningen, Netherlands, 9700RB

Poland

Cityclinic Przychodnia Lekarsko-Psychologiczna Matusiak Spółka Partnerska

Wrocław, Poland

Sponsors and Collaborators

AKARI Therapeutics

More Information

• Responsible Party: AKARI Therapeutics
• ClinicalTrials.gov Identifier: NCT05061771
• Other Study ID Numbers: AK802
• First Posted: September 30, 2021
• Last Update Posted: February 8, 2024
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AKARI Therapeutics:

pemphigoid; blistering skin disease; nomacopan; complement; leukotriene

Additional relevant MeSH terms:

Pemphigoid, Bullous; Skin Diseases, Vesiculobullous; Skin Diseases; Autoimmune Diseases; Immune System Diseases