Hidradenitis Suppurativa (LYRA Study)

Study Description

Brief Summary

The purpose of this study is to evaluate the dose-response of bermekimab efficacy in participants with moderate to severe Hidradenitis Suppurativa (HS).

Condition or Disease

Hidradenitis Suppurativa

Detailed Description

Hidradenitis suppurativa (HS) is a chronic skin disease of unclear etiology that affects 1 percent (%) to 4% of the general population. JNJ-77474462 (bermekimab) is a recombinant human immunoglobulin G1 kappa (IgG1k) monoclonal antibody (mAb) that binds with high affinity and selectivity for human interleukin-1 alpha (IL-1 alpha) and is an effective blocker of IL-1 alpha biological activity. IL-1 alpha is a key mediator of sterile inflammatory responses. Skin is a significant reservoir of preformed IL-1 alpha, and it has been postulated that IL-1 alpha may play a role in the pathophysiology of multiple inflammatory skin disorders, including HS. This study contains 4 study periods: up to 6 weeks screening period (Period 1), 16-week placebo-controlled period (Period 2), 16-week cross over period (Period 3), and 4-week safety follow-up (Period 4). Safety will be assessed by adverse events (AEs), serious adverse event (SAEs), physical examinations, vital signs, electrocardiograms, clinical safety laboratory assessments, allergic reaction, injection-site reactions, and tuberculosis evaluation(s). The total duration of study participation will be up to 42 weeks.

Study Design

Study Type: Interventional  (Clinical Trial)
Estimated Enrollment: 290 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2a/2b, Multicenter, Randomized, Placebo and Active Comparator-controlled, Double-Blind, Dose-ranging Study to Evaluate the Safety and Efficacy of Bermekimab (JNJ-77474462) for the Treatment of Subjects With Moderate to Severe Hidradenitis Suppurativa
Actual Study Start Date: October 12, 2021
Estimated Primary Completion Date: September 8, 2023
Estimated Study Completion Date: April 30, 2024

Outcome Measures

Primary Outcome Measures

  1. Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response-50 (HiSCR50) at Week 16 [ Time Frame: Week 16 ]
    HiSCR50 is defined as at least a 50 percent (%) reduction from baseline in the total abscess and inflammatory nodule (AN) count with no increase in abscess or draining fistula count. Percentage of participants achieving HisCR50 will be reported.

Secondary Outcome Measures

  1. Percentage of Participants Achieving HiSCR75 at Week 16 [ Time Frame: Week 16 ]
    HiSCR75 is defined as at least a 75% reduction from baseline in the total AN count with no increase in abscess or draining fistula count. Percentage of participants achieving HiSCR75 at Week 16 will be reported.
  2. Percentage of Participants Achieving HiSCR90 at Week 16 [ Time Frame: Week 16 ]
    HiSCR90 is defined as at least a 90% reduction from baseline in the total AN count with no increase in abscess or draining fistula count. Percentage of participants achieving HiSCR90 at Week 16 will be reported.
  3. Change from Baseline in the Abscess and Inflammatory Nodule (AN) Count at Week 16 [ Time Frame: Baseline to Week 16 ]
    Change from baseline in the AN count at Week 16 will be reported.
  4. Percentage of Participants Achieving at Least 50%, 75%, 90%, and 100% Reduction in Total AN Count at Week 16 [ Time Frame: Week 16 ]
    Percentage of participants achieving at least 50%, 75%, 90%, and 100% reduction in total AN count at Week 16 will be reported.
  5. Percentage of Participants Achieving an AN Count of 0/1 and 0/1/2 at Week 16 [ Time Frame: Week 16 ]
    Percentage of participants achieving an AN count of 0/1 and 0/1/2 at Week 16 will be reported.
  6. Percentage of Participants Achieving Complete Elimination of Abscesses at Week 16 Among those Participants with Abscesses at Baseline [ Time Frame: Week 16 ]
    Percentage of participants achieving complete elimination of abscesses at Week 16 among those participants with abscesses at baseline will be reported.
  7. Change from Baseline in the Number of Abscesses at Week 16 [ Time Frame: Baseline to Week 16 ]
    Change from baseline in the number of abscesses at Week 16 will be reported.
  8. Percentage of Participants Achieving Complete Elimination of Draining Fistulas at Week 16 Among those Participants with Draining Fistulas at Baseline [ Time Frame: Week 16 ]
    Percentage of participants achieving complete elimination of draining fistulas at Week 16 among those participants with draining fistulas at baseline will be reported.
  9. Change from Baseline in Number of Draining Fistulas at Week 16 [ Time Frame: Baseline to Week 16 ]
    Change from baseline in number of draining fistulas at Week 16 will be reported.
  10. Percentage of Participants Achieving Complete Elimination of Inflammatory Nodules at Week 16 Among those Participants with Inflammatory Nodules at Baseline [ Time Frame: Week 16 ]
    Percentage of participants achieving complete elimination of inflammatory nodules at Week 16 among those participants with inflammatory nodules at baseline will be reported.
  11. Change from Baseline in Number of Inflammatory Nodules at Week 16 [ Time Frame: Baseline to Week 16 ]
    Change from baseline in number of inflammatory nodules at Week 16 will be reported.
  12. Change from Baseline in International Hidradenitis Suppurativa Severity (IHS4) Score at Week 16 [ Time Frame: Baseline to Week 16 ]
    Change from baseline in IHS4 score at Week 16 will be reported. The IHS4 assesses the HS severity and the resulting IHS4 score is arrived at by the number of nodules (multiplied by 1) plus the number of abscesses (multiplied by 2) plus the number of draining tunnels (multiplied by 4). A total score of 3 or less signifies mild, 4-10 signifies moderate and 11 or higher signifies severe disease.
  13. Percentage of Participants with Hidradenitis Suppurativa-Investigator’s Global Assessment (HS-IGA) Score of Inactive (0), Almost Inactive (1), or Mild (2) and with at least 2-grade Improvement Relative to Baseline at Week 16 [¬†Time¬†Frame:¬†Week 16¬†]
    Percentage of participants with HS-IGA score of inactive (0), almost inactive (1), or mild (2) and with at least 2-grade improvement relative to baseline at Week 16 will be reported. The participant’s HS is assessed as inactive (0), almost inactive (1), mild activity (2), moderate activity (3), or severe activity (4). A higher score indicates more severe disease.
  14. Percentage of Participants with HS-IGA Score of Inactive (0) or Almost Inactive (1) at Week 16 Among Participants with HS-IGA Score of Moderate (3) or Severe (4) at Baseline [ Time Frame: Week 16 ]
    Percentage of participants with HS-IGA score of inactive (0) or almost inactive (1) at Week 16 among participants with HS-IGA score of moderate (3) or severe (4) at baseline will be reported.
  15. Change from Baseline in Dermatology Life Quality Index (DLQI) Score at Week 16 [ Time Frame: Baseline to Week 16 ]
    Change from baseline in DLQI score at Week 16 will be reported. The DLQI is a dermatology-specific quality of life (QoL) instrument designed to assess the impact of the disease on a participant’s QoL. It is a 10 item patient-reported outcome(s) (PRO) questionnaire that, in addition to evaluating overall QoL, can be used to assess 6 different aspects that may affect QoL: symptoms and feelings, daily activities, leisure, work or school performance, personal relationships, and treatment. The DLQI produces a numeric score that can range from 0 to 30. A higher score indicates more severe disease.
  16. Change from Baseline in Hidradenitis Suppurativa Symptom Diary (HSSD-24h) Score at Week 16 [ Time Frame: Baseline to Week 16 ]
    Change from baseline in HSSD-24h score at Week 16 will be reported. The HSSD is an 8-item patient self-reported questionnaire that assesses symptoms (including pain, tenderness, pressure, itch, heat, and odor) and signs (including swelling and drainage) of HS. The participants are asked to rate the severity of each symptom on a 0 to 10 numerical rating scale, with 0 indicating no symptom experience and 10 indicating the worst possible symptom experience.
  17. Change from Baseline in Pain Scale Score of HSSD- 24h at Week 16 [ Time Frame: Baseline to Week 16 ]
    Change from baseline in pain scale score of HSSD-24h score at Week 16 will be reported. The HSSD is an 8-item patient self-reported questionnaire that assesses symptoms (including pain, tenderness, pressure, itch, heat, and odor) and signs (including swelling and drainage) of HS. The participants are asked to rate the severity of each symptom on a 0 to 10 numerical rating scale, with 0 indicating no symptom experience and 10 indicating the worst possible symptom experience.
  18. Change from Baseline in Itch Scale Score of HSSD- 24h at Week 16 [ Time Frame: Baseline to Week 16 ]
    Change from baseline in itch scale score of HSSD- 24h at Week 16 will be reported. The HSSD is an 8-item patient self-reported questionnaire that assesses symptoms (including pain, tenderness, pressure, itch, heat, and odor) and signs (including swelling and drainage) of HS. The participants are asked to rate the severity of each symptom on a 0 to 10 numerical rating scale, with 0 indicating no symptom experience and 10 indicating the worst possible symptom experience.
  19. Percentage of Participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to Week 36 ]
    An adverse event (AEs) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs are AEs with onset during the treatment phase or that are a consequence of a pre-existing condition that has worsened since baseline.
  20. Percentage of Participants with Treatment-emergent Serious Adverse Events (SAEs) [ Time Frame: Up to Week 36 ]
    SAE is any untoward medical occurrence that at any dose may results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product. Treatment-emergent SAEs are defined as SAEs with onset or worsening on or after date of first dose of study treatment.
  21. Percentage of Participants with Abnormalities in Laboratory Parameters [ Time Frame: Up to Week 36 ]
    Percentage of participants with abnormalities in laboratory parameters (hematology, clinical chemistry) will be reported.
  22. Serum Concentration of Bermekimab [ Time Frame: Up to Week 36 ]
    Serum concentration of bermekimab will be assessed over time.
  23. Number of Participants with Antibodies to Bermekimab [ Time Frame: Up to Week 36 ]
    Number of participants with antibodies to bermekimab will be reported.

Eligibility Criteria

Ages Eligible for Study:   12 Years and older (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers: No

Inclusion Criteria

  • Have hidradenitis suppurativa (HS) for at least 1 year (365 days) prior to the baseline visit as determined by the investigator through participant interview and/or review of the medical history
  • Have Hurley Stage II or Hurley Stage III HS as determined by the investigator at screening and baseline visits
  • Have HS lesions present in at least 2 distinct anatomic areas (examples include but are not limited to left and right axilla; or left axilla and left inguinocrural fold) at screening and baseline visits
  • Have a total abscess and inflammatory nodule (AN) count of greater than or equal to (>=)5 at the screening and baseline visit
  • Agree not to receive a live virus or live bacterial vaccination during the study and for 90 days after the last administration of study intervention

Exclusion Criteria

  • Has a current diagnosis or signs or symptoms of severe, progressive, or uncontrolled renal, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
  • Has unstable cardiovascular disease, defined as a recent clinical deterioration (that is, unstable angina, rapid atrial fibrillation) in the last 3 months or a cardiac hospitalization within the last 3 months
  • Has or has had herpes zoster within the 2 months before screening
  • Has a transplanted organ (with exception of a corneal transplant greater than [>]3 months before the first administration of study intervention)
  • Has known allergies, hypersensitivity, or intolerance to bermekimab or adalimumab or its excipients
ADDITIONAL DETAILS