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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.

A Study of Bermekimab for the Treatment of Participants with Moderate to Severe Hidradenitis Suppurativa (LYRA)

151

Baseline characteristics were balanced across the treatment groups. A total of 68 (45%) participants were male. Majority of the participants were white (101 [69.7%]). The median age was 35 years (range 18 to 74 years) with majority of the participants under 40 years of age (93 [61.6%]). The mean (SD) body mass index (BMI) of the study population was 36.0 (10.44) kilograms/meter square (kg/m^2). The demographic characteristics were comparable across treatment groups. The majority of participants (105 [69.5%]) had Hurley stage II classification of HS. The study population had HS for a mean (SD) duration of 12.7 (9.52) years. The mean (SD) AN count was 10.9 (6.29); The mean (SD) number of draining fistula among the study population was 2.3 (2.81).

A total of 231 HS participants were screened out of which a total of 151 participants were enrolled and randomized in Part 1 to receive bermekimab 1050 mg (51 participants), adalimumab 160 mg (50 participants), and placebo (50 participants). Of the 151 enrolled participants included in the full analysis set, 86 participants (30 in bermekimab and 28 each in adalimumab and placebo) completed Week 16. 26 participants (9 in bermekimab, 10 in adalimumab, and 7 in placebo to bermekimab) completed study participation prior to Week 36. 65 participants (21 in bermekimab, 22 each in adalimumab and placebo) discontinued study participation prior to Week 16 before termination of the study at the Sponsor's discretion, of which 13 participants (4 in bermekimab, 3 in adalimumab, and 6 in placebo) completed the safety follow-up. The remaining 52 participants did not complete the safety follow-up: 8 lost to follow-ups, 10 withdrew from the study, 1 participant died, and 28 participants due to trial termination. A total of 125 participants (42 in bermekimab, 40 in adalimumab, 22 in placebo, and 21 in placebo to bermekimab) discontinued the study participation prior to Week 36, of these 26 participants (10 in bermekimab, 5 in adalimumab, 6 in placebo, and 5 in placebo to bermekimab) completed the safety follow-up. The remaining 99 participants did not complete the safety follow-up: 15 lost to follow-ups, 16 participants withdrew from the study, 1 participant died, and 59 participants due to trial termination. Parts 2 of the study were planned but were not executed due to early study termination at the Sponsor's discretion.

Of the 151 treated participants, 102 participants experienced 1 or more TEAEs through Week 16: 38 (74.5%) participants from the bermekimab group, 31 (62.0%) participants from the placebo group, and 33 (66.0%) from the adalimumab group. The proportions of participants with 1 or more TEAEs were comparable across all the treatment group. Nine participants experienced TEAEs that were severe in intensity as assessed by the investigator: 3 (5.9%) participants from the bermekimab group, 2 (4.0%) participants from the placebo group, and 4 (8.0%) participants from the adalimumab group. The proportions of participants with related TEAEs (>=1) through Week 16 were higher in the bermekimab group (25 [49.0%]) in comparison to placebo (10 [20.0%]) and adalimumab (19 [38.0%]) group. Through Week 36, 110 participants experienced 1 or more TEAEs: 39 (76.5%) from the bermekimab group (inclusive of 13 (46.4%) participants who transitioned from the placebo to the bermekimab 1050 mg group between Weeks 16 through 36), 31 (62.0%) participants from the placebo group, and 40 (80.0%) participants from the adalimumab group. The frequency of events by SOC and PT at Week 36 was comparable to the data through Week 16. Ten participants experienced TEAEs that were severe in intensity as assessed by the investigator: 4 (7.8%) participants from the bermekimab group (no severe TEAEs were reported in participants crossed over to bermekimab from placebo), 2 (4.0%) participants from the placebo group, and 4 (8.0%) participants from the adalimumab group. One participant from the adalimumab group died due to illicit drug exposure. This SAE was assessed as not related to study intervention by the investigator and the Sponsor. Six participants experienced treatment-emergent SAEs in the study: 1 (2.0%) participant from the bermekimab group, 1 (2.0%) participant from the placebo group, and 4 (8.0%) participants from the adalimumab group. Injection-Site Reactions Through Week 16, eight participants experienced injection-site reactions: 7 (13.5%) from the bermekimab group and 1 (0.7%) from the placebo group. No injection-site reactions were reported in the adalimumab group. The participant from the placebo group experienced 1 incidence of injection site pain. In the bermekimab group, 4 (7.7%) incidents of injection site erythema, 3 (5.8%) incidents of injection site pruritus, and 1 (1.9%) incident of injection site haematoma were reported. Clinical Laboratory Values Data showed no clinically meaningful changes in hematology or clinical chemistry values. The results were comparable across study groups.

Efficacy Endpoints Efficacy analysis was based on the modified full analysis set which included participants who could have reached a visit by the time of the decision was made to terminate the study on 14 October 2022. Participants were excluded from the analysis after projected visit (projected visit [weeks] = [decision date of study termination - first dose date +1] /7). Due to early termination of the study, the number of participants available for evaluation after Week 16 was small. Hence, the data was difficult to interpret. Primary Efficacy Endpoint Proportion of Participants Achieving HiSCR50 at Week 16 At Week 16, 13 (37.1%) of the 35 bermekimab-treated participants achieved HiSCR50. The proportion of HiSCR50 achievers was comparable between the bermekimab 1050 mg and placebo (13 [37.1%] each) groups (p=1.000). The proportion of participants achieving HiSCR50 was numerically higher in the adalimumab group at Week 16 in comparison to the placebo group (20 [57.1%] versus 13 [37.1%], respectively; p=0.098). Similar findings were observed in the supplementary analysis, where bermekimab 1050 mg did not exhibit superior efficacy than placebo in HS participants (p=0.904). Secondary Efficacy Endpoint Proportion of Participants Achieving HiSCR75 and HiSCR90 at Week 16 At Week 16, 25.7% (9) and 17.1% (6) of the bermekimab-treated participants achieved HiSCR75 and HiSCR90, respectively. The proportions of HiSCR75 and HiSCR90 achievers in the bermekimab 1050 mg group were comparable with placebo group (9 [25.7%] and 5 [14.3%], respectively) (p=1.000 and 0.746, respectively). The proportion of HiSCR75 and HiSCR90 achievers at Week 16 in the adalimumab group was numerically higher than the placebo group (14 [40.0%]; p=0.209, and 8 [22.9%]; p=0.350, respectively). Post Week 16, participants from the placebo group crossed over to the bermekimab 1050 mg group. The proportion of participants who achieved HiSCR50 through Week 36 was small that is, the data was difficult to interpret. Change from Baseline in Inflammatory Nodules Count A notable but not clinically significant mean (SD) reduction in the number of inflammatory nodules from baseline to Week 16 was observed in the bermekimab-treated participants (-4.48 [7.689]) compared with the placebo group (-3.64 [5.258]; p=0.621). Change from Baseline in Abscess Count A mean (SD) reduction of -0.83 (3.071) in abscess count at Week 16 from baseline was observed in the bermekimab-treated participants which was comparable with placebo (-0.86 [1.900]; p=0.796). Change from Baseline in Abscess Inflammatory Nodules (AN) Count A notable but not clinically significant mean (SD) reduction in AN count from baseline to Week 16 was observed in the bermekimab-treated participants (-5.31 [8.59]) compared with the placebo group (-4.50 [5.088]; p=0.381). Change from Baseline in Number of Draining Fistulas A mean (SD) change in draining fistula from baseline was prominent in the bermekimab-treated participants (-1.00 [1.626]) compared to the placebo group (-0.04 [1.915]; p=0.487). No clinically significant difference in reduction of draining fistula (from baseline) was observed between the adalimumab and placebo groups (-0.2 [-1.05, 0.57]; p=0.626). Due to early termination of the study, the number of participants available for evaluation after Week 16 was small. Hence, the data was difficult to interpret. Secondary Pharmacokinetics Endpoint: Serum Concentration of Bermekimab Over Time The steady-state trough serum bermekimab appeared to be achieved by Week 4. The mean and median steady-state trough serum bermekimab concentrations were 78.46 and 71.97 micrograms per milliliter (mcg/mL), respectively. For the placebo to bermekimab 1050 mg qw cross-over group, the mean and median steady-state trough serum bermekimab concentrations at Week 20 were 64.30 and 69.72 mcg/mL, respectively. Secondary Immunogenicity Endpoint: Through Weeks 16 and 36, a total of 47 and 73 participants, respectively, who received at least 1 complete dose of bermekimab and had at least 1 valid blood sample drawn for the detection of antibodies to bermekimab were included in the evaluation of antibodies to bermekimab. Participants who received placebo only were excluded from the evaluation of antibodies to bermekimab. Percentage of Participants with Antibodies to Bermekimab The overall incidence of antibodies to bermekimab was 12.8% (6/47) through Week 16 and 21.9% (16/73) through Week 36. Among the 16 participants who were positive for antibodies to bermekimab through Week 36, 4 (15.4%) and 12 (25.5%) participants were in the placebo to bermekimab 1050 mg qw cross-over group and bermekimab 1050 mg qw group, respectively.

Bermekimab showed numerically high response in the reduction of inflammatory nodule and draining fistula counts but did not result in statistically significant increase in HiSCR50 responder as compared to placebo at Week 16. The study met its prespecified futility criteria; hence, the decision was made to terminate this study. Bermekimab 1050 mg was well tolerated in participants with HS; however, it showed numerically higher incidence of infections and infestations and injection site reactions.

Nov. 23, 2023

Yes

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

https://jrct.mhlw.go.jp/latest-detail/jRCT2031210308

Nishikawa Kazuko

Janssen Pharmaceutical K.K.

5-2, Nishi-kanda 3-chome, Chiyoda-ku, Tokyo

DL-JANJP-JCO_TL_TSG_EMP@its.jnj.com

Medical Information Center

Janssen Pharmaceutical K.K.

5-2, Nishi-kanda 3-chome, Chiyoda-ku, Tokyo

+81-120-183-275

DL-JANJP-JCO_TL_TSG_EMP@its.jnj.com

Complete

Feb. 04, 2022

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

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

Both

Hidradenitis Suppurativa

Bermekimab
Bermekimab will be administered subcutaneously.
Part 1 (Group1): Placebo
Part 1 (Group 3):Bermekimab Dose 1
Part 2 (Group 1):Placebo
Part 2 (Group 2):Bermekimab Dose 1
Part 2 (Group 3):Bermekimab Dose 1
Part 2 (Group 4):Bermekimab Dose 2

Adalimumab
Adalimumab will be administered subcutaneously.
Part 1 (Group 2):Adalimumab

Placebo
Placebo will be administered subcutaneously.
Part 1 (Group1): Placebo
Part 1 (Group 2):Adalimumab
Part 1 (Group 3):Bermekimab Dose 1
Part 2 (Group 1):Placebo
Part 2 (Group 3):Bermekimab Dose 1
Part 2 (Group 4):Bermekimab Dose 2

-Part 1: Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response-50 (HiSCR50) at 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.

-Part 2: Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response-50 (HiSCR50) at Week 12
HiSCR50 is defined as at least a 50 percent reduction from baseline in the total AN count with no increase in abscess or draining fistula count. Percentage of participants achieving HisCR50 will be reported.

-Part 1 and Part 2: Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response-75 (HiSCR75)
Part 1: Week 16; Part 2: Week 12
HiSCR75 is defined as at least a 75 percent reduction from baseline in the total AN count with no increase in abscess or draining fistula count. Percentage of participants achieving HiSCR75 will be reported.

-Part 1 and Part 2: Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response-90 (HiSCR90)
Part 1: Week 16; Part 2: Week 12
HiSCR90 is defined as at least a 90 percent reduction from baseline in the total AN count with no increase in abscess or draining fistula count. Percentage of participants achieving HiSCR90 will be reported.

Parts 1 and 2: Change from Baseline in the (AN) Count
Part 1: Baseline and Week 16; Part 2: Baseline and Week 12
Change from baseline in the AN count will be reported.

-Parts 1 and 2: Percentage of Participants Achieving at Least 50 percent, 75 percent, 90 percent, and 100 percent Reduction in Total AN Count
Part 1: Week 16; Part 2: Week 12
Percentage of participants achieving at least 50 percent, 75 percent, 90 percent, and 100 percent reduction in total AN count will be reported.

-Parts 1 and 2: Percentage of Participants Achieving an AN Count of 0/1 and 0/1/2
Part 1: Week 16; Part 2: Week 12
Percentage of participants achieving an AN count of 0/1 and 0/1/2 will be reported.

-Parts 1 and 2: Percentage of Participants Achieving Complete Elimination of Abscesses Among those Participants with Abscesses at Baseline
Part 1: Week 16; Part 2: Week 12
Percentage of participants achieving complete elimination of abscesses among those participants with abscesses at baseline will be reported.

-Parts 1 and 2: Change from Baseline in the Number of Abscesses
Part 1: Baseline and Week 16; Part 2: Baseline and Week 12
Change from baseline in the number of abscesses will be reported.

-Parts 1 and 2: Percentage of Participants Achieving Complete Elimination of Draining Fistulas Among those Participants with Draining Fistulas at Baseline
Part 1: Week 16; Part 2: Week 12
Percentage of participants achieving complete elimination of abscesses among those participants with abscesses at baseline will be reported.

-Parts 1 and 2: Change from Baseline in Number of Draining Fistulas
Part 1: Baseline and Week 16; Part 2: Baseline and Week 12
Change from baseline in number of draining fistulas will be reported.

- Parts 1 and 2: Percentage of Participants Achieving Complete Elimination of Inflammatory Nodules Among those Participants with Inflammatory Nodules at Baseline
Part 1: Week 16; Part 2: Week 12
Percentage of participants achieving complete elimination of inflammatory nodules among those participants with inflammatory nodules at baseline will be reported.

-Parts 1 and 2: Change from Baseline in Number of Inflammatory Nodules
Part 1: Baseline and Week 16; Part 2: Baseline and Week 12
Change from baseline in number of inflammatory nodules will be reported.

-Parts 1 and 2: Change from Baseline in International Hidradenitis Suppurativa Severity (IHS4) Score
Part 1: Baseline and Week 16; Part 2: Baseline and Week 12
Change from baseline in IHS4 score will be reported. The IHS4 assesses the Hidradenitis Suppurativa (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.

-Parts 1 and 2: Percentage of Participants with Hidradenitis Suppurativa-Investigato's Global Assessment (HS-IGA) Score of Inactive (0), Almost Inactive (1), or Mild (2) and with at least 2-grade
Part 1: Week 16; Part 2: Week 12
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 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.

-Parts 1 and 2: Percentage of Participants with HS-IGA Score of Inactive (0) or Almost Inactive (1) Among Participants with HS-IGA Score of Moderate (3) or Severe (4) at Baseline
Part 1: Week 16; Part 2: Week 12
Percentage of participants with HS-IGA score of inactive (0) or almost inactive (1) among participants with HS-IGA score of moderate (3) or severe (4) at baseline will be reported.

-Parts 1 and 2: Change from Baseline in Dermatology Life Quality Index (DLQI) Score
Part 1: Baseline and Week 16; Part 2: Baseline and Week 12
Change from baseline in DLQI score 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.

-Parts 1 and 2: Change from Baseline in Hidradenitis Suppurativa Symptom Diary (HSSD-24 Hour) Score
Part 1: Baseline and Week 16; Part 2: Baseline and Week 12
Change from baseline in HSSD-24 hour score 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.

-Parts 1 and 2: Change from Baseline in Pain Scale Score of HSSD-24 Hour
Part 1: Baseline and Week 16; Part 2: Baseline and Week 12
Change from baseline in pain scale score of HSSD-24 hour score 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.

-Parts 1 and 2: Change from Baseline in Itch Scale Score of HSSD-24 Hour
Part 1: Baseline and Week 16; Part 2: Baseline and Week 12
Change from baseline in itch scale score of HSSD-24 hour 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.

-Parts 1 and 2: Percentage of Participants with Treatment-emergent Adverse Events (TEAEs)
Up to Week 36
An adverse event (AE) 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.

See the attached pdf for the remaining.

Sept. 17, 2021

Germany/Netherlands/United States of America/Australia/Canada/Poland/Spain