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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Bullous Pemphigoid

Intervention / Treatment
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* Drug: nomacopan (rVA576)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Male or female ≥90 years of age at the time of consent with Karnofsky score of 70% or more at screening Diagnosis of Bullous Pemphigoid either newly diagnosed or relapsing Patients with confirmed atypical Bullous Pemphigoid Bullous Pemphigoid classified as either moderate or severe on the basis of the Investigator Global Assessment (IGA) at randomisation Willing to receive immunisation against Neisseria meningitidis and/or antibiotic prophylaxis Provision of voluntary written informed consent Exclusion Criteria: 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 Epidermolysis bullosa acquisita, mucous membrane pemphigoid, or anti p200 pemphigoid Mucosal lesions BPDAI score accounts for ≥30% of total BPDAI activity score at randomisation BP considered to be drug induced, in particular diagnosis of BP made within two months of starting a drug well known to induce BP 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. Taking > 0.3 mg/kg/day OCS at screening Treatment with systemic immunomodulators such as dapsone or doxycycline within four half-lives of the drugs prior to baseline Day 1 Treatment with immunosuppressants within the last two weeks prior to baseline Treatment with an anti-complement therapy or with Zileuton within the last three months prior to baseline OCS dose no more than 0.3mg/kg/day in the 7 days before screening visit Taking super-potent topical corticosteroids and unable to discontinue them at or before the screening assessment Active systemic or organ system bacterial or fungal infection or progressive severe infection Known congenital immunodeficiency or a history of acquired immunodeficiency including a positive human immunodeficiency virus (HIV) test Active infection with hepatitis B or C Positive nasal throat swab for Neisseria species Known hypersensitivity to nomacopan and any of its excipients Receipt of live attenuated vaccines within 2 weeks of Day 1

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: nomacopan (rVA576)<br>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)<br>* Nomacopan an inhibitor of complement C5 and LTB4<br>|
| Placebo Comparator: Placebo<br>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<br>* Placebo<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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leukotriene, pemphigoid, blistering skin disease, nomacopan, complement