Bullous Pemphigoid
Conditions
Keywords
pemphigoid, blistering skin disease, nomacopan, complement, leukotriene
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.
Interventions
Nomacopan an inhibitor of complement C5 and LTB4
OTHERPlacebo
Placebo
Sponsors
AKARI Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Achievement of Complete Disease Remission | weeks 16 - 24 | Proportion of patients in Complete Disease Remission |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients requiring rescue therapy | Randomization to 24 weeks | Proportion of patients requiring rescue therapy during the 24 weeks of treatment |
| 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 |
| Duration of Complete and Partial Disease Remission | week 6 to 24 | Duration (weeks) of Complete Disease Remission and Partial Disease Remission |
| Cumulative oral corticosteroid, OCS, during treatment | Randomization to 24 weeks | Cumulative OCS used during treatment |
| Adverse Events | Day 1 to Week 28 | Frequency, type and relationship of AEs to treatment |
| 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) |
| 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 |
| Investigator Global Assessment (IGA) score | weeks 6 - 24 | Proportion of patients with Investigator Global Assessment (IGA) score of 0 or 1 |
Countries
Germany, Netherlands, Poland, United States
Outcome results
None listed