Hidradenitis Suppurativa
Conditions
Keywords
Bruton's tyrosine kinase (BTK) inhibitor, Hidradenitis Suppurativa, HS, Hidradenitis Suppurativa clinical response, HiSCR, remibrutinib, LOU064, Hidradenitides, Suppurativa, Hidradenitis, Suppurativa, Suppurativa Hidradenitides, Suppurativa Hidradenitis, Acne inversa,, Verneuil disease, Inflammatory skin disease, Chronic skin condition
Brief summary
The purpose of this study is to establish the efficacy, safety, and tolerability of remibrutinib (LOU064) Dose A and Dose B compared to placebo in participants with moderate to severe hidradenitis suppurativa (HS).
Detailed description
The total duration of the study is 76 weeks and consists of: Screening (up to 4 weeks), Treatment Period 1 (16 weeks, double-blind treatment with remibrutinib (Dose A or Dose B) or placebo, Treatment Period 2 (52 weeks, treatment with remibrutinib (Dose A or Dose B) and Safety Follow-Up (treatment-free follow-up for 4 weeks). Participants who prematurely discontinue study treatment (either during Treatment Period 1 or Treatment Period 2) are encouraged to remain in the study. Participants who do not wish to remain in the study will enter a 4-week Safety Follow-Up period.
Interventions
Remibrutinib Dose A (oral)
Remibrutinib Dose B (oral)
DRUGPlacebo 1
Placebo matching to remibrutinib Dose A (oral)
DRUGPlacebo 2
Placebo matching to remibrutinib Dose B (oral)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Male and female participants ≥ 12 years of age at the time of signing of the informed consent. 2. Diagnosis of HS based on clinical history and physical examination for at least 6 months prior to the Baseline visit. 3. Participants with moderate to severe HS defined as: * A total of at least 5 AN count (abscesses and/or inflammatory nodules) AND * Inflammatory lesions should affect at least 2 distinct anatomic areas (e.g., left and right axillae) Key
Exclusion criteria
1. Presence of more than 20 fistulae/tunnels (both draining and non-draining) in total at baseline. 2. Any active skin disease or conditions that may interfere with the assessment of HS. 3. Previous exposure to remibrutinib or other BTK inhibitors. 4. Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days (for small molecules) prior to randomization, or until the pharmacodynamic effect has returned to baseline (for biologics), whichever is longer. 5. Significant bleeding risk or coagulation disorders. 6. History of gastrointestinal bleeding. 7. Requirement for anti-platelet (except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75 mg/d) or anti-coagulant medication. 8. History or current hepatic disease. 9. Evidence of clinically significant cardiovascular, neurological, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, hematological disorders, gastrointestinal disease or immunodeficiency that, in the Investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant. 10. History of hypersensitivity to any of the study drug constituents. 11. Known or suspected infectious disease that is active, chronic or recurrent which precludes the participant from participating in the trial as per investigator's assessment. These infectious diseases include and are not limited to opportunistic infections (e.g., tuberculosis, atypical mycobacterioses, listeriosis or aspergillosis) and/or known or suspected Human Immunodeficiency Virus (HIV) infection. Should it be required by local regulations and/or considered appropriate by the investigator, an HIV test can be performed to confirm eligibility. 12. History of live attenuated vaccine administration within 6 weeks prior to randomization or requirement to receive these vaccinations at any time while on study treatment. 13. Major surgery within 8 weeks prior to screening or planned surgery for the duration of the study. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with Hidradenitis Suppurativa clinical response 50 (HiSCR50) at Week 16 | Week 16 | HiSCR50 is defined as at least a 50% decrease in Abscess and Inflammatory Nodule (AN) count with no increase in the number of abscesses and in the number of draining tunnels/fistulae compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with Abscesses and inflammatory nodules 50 (AN50) response at Week 16 | Week 16 | AN50 is defined as at least a 50% decrease in Abscess and Inflammatory Nodule (AN) count compared to baseline |
| Percentage change from baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) at Week 16 | From baseline up to Week 16 | The IHS4 is a disease severity scoring system developed by the European Hidradenitis Suppurativa Foundation. It is a weighted sum of different types of inflammatory lesion counts, calculated as 1 x number of nodules + 2 x number of abscesses + 4 x number of draining tunnels (=fistulae=sinuses). |
| Proportion of participants with HiSCR75 response at Week 16 | Week 16 | HiSCR75 is defined as at least a 75% decrease in Abscess and Inflammatory Nodule (AN) count with no increase in the number of abscesses and in the number of draining tunnels/fistulae compared to baseline. |
| Proportion of participants experiencing Hidradenitis Suppurativa (HS) flares at Week 16 | Up to Week 16 | Flare is defined as at least a 25% increase in AN count with a minimum increase of 2 AN relative to baseline. |
| Proportion of participants with HiSCR50 response at Week 8 | Week 8 | HiSCR50 is defined as at least a 50% decrease in Abscess and Inflammatory Nodule (AN) count with no increase in the number of abscesses and in the number of draining tunnels/fistulae compared to baseline. |
| Proportion of participants with HiSCR90 response at Week 16 | Week 16 | HiSCR90 is defined as at least a 90% decrease in Abscess and Inflammatory Nodule (AN) count with no increase in the number of abscesses and in the number of draining tunnels/fistulae compared to baseline. |
| Proportion of participants with clinical response in HS related skin pain (NRS 30), at worst at Week 16 | Week 16 | Achievement of NRS30 at Week 16, among participants with baseline NRS ≥ 3 (pooled data from studies CLOU064J12301 and CLOU064J12302). NRS30 is defined as at least a 30% reduction and at least 2-unit reduction from baseline in Patient's Global Assessment of Skin Pain - at worst over the past 7 days. |
| Incidence of treatment emergent adverse events and serious adverse events during the study | From randomization to end of study, assessed up to 72 weeks. | The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. |
Countries
Argentina, Australia, Bulgaria, Canada, China, Colombia, Denmark, Germany, Greece, Italy, Malaysia, Mexico, Poland, Portugal, Slovakia, South Africa, Spain, Switzerland, Taiwan, United States
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed