臨床研究等提出・公開システム

A randomized, double-blind, multicenter study assessing short (16 weeks) and long-term efficacy (up to 1 year), safety, and tolerability of 2 subcutaneous secukinumab dose regimens in adult patients with moderate to severe hidradenitis suppurativa (SUNSHINE)

Study of efficacy and safety of two secukinumab dose regimens in subjects with moderate to severe hidradenitis suppurativa

544

The mean age of the participants was 36.1 years (SD: 11.69), with the Secukinumab 300 mg every 2 weeks group (hereinafter the Q2W), the Secukinumab 300 mg every 4 weeks group (hereinafter the Q4W), and the placebo group having mean ages were 37.1 years (SD: 12.53), 35.7 years (SD: 11.71) and 35.5 years (SD: 10.75), respectively. In the overall population, most participants were in the between 18 and 64 years age group (98.7%), with only a small proportion aged 65 or over (1.3%). Marginally higher number of females (56.2%) were enrolled than the males (43.8%). The proportion of female participants was 56.4%, 55.6% and 56.7% in the Q2W, Q4W and placebo group, respectively. Majority of the participants were White (79.5%). Among white subjects, the rates were 80.1%, 81.1% and 77.2% in the Q2W, Q4W and placebo group, respectively.

Overall, 544 participants were randomized, and 168 (/182) in the Q2W group, 169 (/181) in the Q4W group, and 172 (/181) in the placebo group completed Treatment Period 1, which lasted 16 weeks. The number of participants who dropped out during this period was 14 (/182), 12 (/181), and 9 (/181) participants in each group. The main reason for withdrawal was withdrawal by subject, with 4, 9 and 5 participants in each group respectively. Of the participants who completed Treatment Period 1, 131 (/168) in the Q2W, 137 (/169) in the Q4W, 68 (/85) in the placebo group who were re-randomized to the Q2W group, and 75(/87) from the placebo group who were re-randomized to the Q4W group, completed Treatment Period 2. The number of participants who dropped out during this period was 37 (/168), 32 (/169), 17 (/85) and 12 (/87) participants in each group. The main reason for withdrawal was withdrawal by subject, with 26, 20, 10 and 6 participants in each group, respectively

Adverse events were compiled from events reported over the 60-week period from the first administration of the investigational drug until the end of the trial (during the conduct of the trial and safety follow-up). Note that the data for the placebo group were compiled from Treatment Period 1 (16 weeks). Serious adverse events were reported in 13 out of 181 participants (7.18%) in the Q2W group, 9 out of 180 participants (5.00%) in the Q4W group, and 6 out of 180 participants (3.33%) in the placebo group. Serious adverse events reported in two or more participants in any of the Secukinumab 300 mg treatment groups were as follows; in the Q2W group, in the Q4W group, and placebo group, hidradenitis occurred in 3 out of 181 participants (1.66%), 3 out of 180 participants (1.67%), and 2 out of 180 participants (1.11%), respectively; sweat gland infections were 1 out of 181 (0.55%), 3 out of 180 participants (1.67%), and 0 out of 180 participants (0.00%), respectively. Non-serious treatment-emergent adverse event was reported in 135 out of 181 participants (74.59%) in the Q2W group, 132 out of 180 participants (73.33%) in the Q4W group and 88 out of 180 participants (48.89%) in the placebo group. The common adverse events (incidence rate >=5% in any of the Secukinumab 300 mg treatment groups) were as follows in order of the Q2W group (181 participants), the Q4W group (180 participants), and the placebo group (180 participants); diarrhoea [n (%)], 11 (6.08%), 16 (8.89%), 9 (5.00%); fatigue, 6 (3.31%), 11 (6.11%), 8 (4.44%); pyrexia, 13 (7.18%), 8 (4.44%), 2 (1.11%); nasopharyngitis, 32 (17.68%), 24 (13.33%), 13 (7.22%); upper respiratory tract infection, 9 (4.97%), 13 (7.22%), 4 (2.22%); arthralgia, 11 (6.08%), 6 (3.33%), 8 (4.44%); headache, 33 (18.32%), 32 (17.78%), 14 (7.78%); hidradenitis, 16 (8.84%), 17 (9.44%), 23 (12.78%); intertrigo, 10 (5.52%), 7 (3.89%), 2 (1.11%); pruritus, 11 (6.08%), 6 (3.33%), 2 (1.11%).

Among those in the Q2W group, 45.0% were responders of the HiSCR (Hidradenitis Suppurativa Clinical Response) 50 response at week 16, and 41.8% in the Q4W group, compared to 33.7% in the placebo group. The Q2W group showed significantly higher efficacy compared to placebo [Odds Ratio: 1.75; (2-sided) 95% CI: 1.12, 2.73; one-sided p-value 0.0070, logistic regression]. The odds ratio was not statistically significant between Q4W group and placebo [Odds Ratio: 1.48; (2-sided) 95% CI: 0.95, 2.32; one-sided p-value 0.0418, logistic regression].

In the Q2W group, a statistically significant improvement in the HiSCR50 response at week 16 (primary endpoint) was observed compared with placebo. The Q4W group did not achieve statistically significant differences; however, it demonstrated the reductions in signs and symptoms of hidradenitis suppurativa. These findings support the efficacy of IL-17A inhibition in reducing the disease activity. The tolerability of Secukinumab was good, and no new significant safety concerns were identified.

Yes

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Yamada Hiroyuki

Novartis Pharma. K.K.

Toranomon Hills Mori Tower 23-1, Toranomon 1-chome Minato-ku, Tokyo 105-6333, Japan

rinshoshiken.toroku@novartis.com

Yamada Hiroyuki

Novartis Pharma. K.K.

Toranomon Hills Mori Tower 23-1, Toranomon 1-chome Minato-ku, Tokyo 105-6333, Japan

+81-120-003-293

rinshoshiken.toroku@novartis.com

completed

April. 30, 2019

Interventional

This is a multicenter, randomized, double-blind, placebo controlled, parallel group study with two secukinumab dose regimens in approximately 541 patients with moderate tosevere HS.

treatment purpose

3

- Diagnosis of HS >= 1 year prior to baseline.
- Patients with moderate to severe HS defined as:
A total of at least 5 inflammatory lesions, i.e. abscesses and/or inflammatory nodules AND Inflammatory lesions should affect at least 2 distinct anatomic areas
- Patients agree to daily use of topical over-the-counter antiseptics on the areas affected by HS lesions while on study treatment.

- Total fistulae count >= 20 at baseline.
- Any other active skin disease or condition that may interfere with assessment of HS.
- Active ongoing inflammatory diseases other than HS that require treatment with prohibited medications.
- Use or planned use of prohibited treatment. Washout periods detailed in the protocol have to be adhered to.
- History of hypersensitivity to any of the study drug constituents.
- History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system treated or untreated within the past 5 years, regardless of whether there is evidence of local recurrence or metastases (except for skin Bowen's disease, or basal cell carcinoma or actinic keratoses that have been treated with no evidence of recurrence in the past 12 weeks; carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed).
- Pregnant or lactating women.

Both

Hidradenitis Suppurativa

investigational material(s)
Generic name etc :
INN of investigational material : Secukinumab
Therapeutic category code : 399 Agents affecting metabolism, n.e.c.
Dosage and Administration for Investigational material : Secukinumab 300mg every 2 or every 4 weeks

control material(s)
Generic name etc :
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material :Placebo 300mg every 2 or every 4 weeks

efficacy
Proportion of participants with Hidradenitis Suppurativa clinical response (HiSCR) [ Time Frame: 16 weeks ]
HiSCR is defined as at least a 50% decrease in Abscess and Inflammatory Nodule (AN) count with no increase in the number of abscesses and/or in the number of draining fistulae.

Jan. 24, 2019