臨床研究等提出・公開システム

A randomized, double-blind, placebo- and active controlled multicenter trial to demonstrate efficacy of subcutaneous secukinumab compared to placebo and etanercept (in a single-blinded arm) after twelve weeks of treatment, and to assess the safety, tolerability, and long-term efficacy in subjects from 6 to less than 18 years of age with severe chronic plaque psoriasis

Study of efficacy and safety of secukinumab in pediatric patients with severe plaque psoriasis

162

The mean (SD) age of all 162 randomized patients was 13.5 (3.06) years. Out of all, 125 patients were in the age group of >= 12 years, and 37 patients were in the age group of < 12 years. The patients were predominantly caucasian (82.7%). There were more females (59.9%) than males (40.1%).

A total of 187 patients were screened, of which 162 were randomized. Of these, 39/40 patients in the AIN457 low dose arm, 38/40 patients in AIN457 high dose arm, 39/41 patients in the placebo arm and 40/41 patients in the etanercept arm completed the study treatment up to Week 12. After Week 12, all patients except 5 placebo-patients continued the study treatment and, in the placebo arm, switched to the AIN457 low dose group (N = 16) or the AIN457 high dose group (N = 18). The number of patients who continued study treatment from Week 12 to Week 52 was 53/55 patients in AIN457 low dose arm, 53/56 patients in AIN457 high dose arm and 34/40 patients in the etanercept arm. Further, 39/53 patients in AIN457 low dose arm and 43/53 patients in AIN457 high dose arm continued the study treatment from Week 52 to Week 236.

No deaths were reported during the study. During the treatment period, each AIN457 dose arms (low and high dose) had comparable numbers of patients with SAEs: 7/56 (12.5%) patients in the AIN457 low dose arm and 8/58 (13.8%) patients in the AIN457 high dose arm. The SAEs in the SOC of Infections and infestations were the most common in each AIN457 dose arms, low dose: 2/56 (3.6%) and high dose: 3/58 (5.2%), affecting by PTs of bronchitis, cellulitis in 1 patient each from AIN457 low dose arm and enterocolitis bacterial, infectious pleural effusion, lung abscess, pneumonia, toxic shock syndrome in 1 patient each from AIN457 high dose arm. Also, no other SAE occurred in more than 1 patient. The most frequently reported non-serious adverse events (by PTs, at least 10% in any AIN457 dose arms) included nasopharyngitis (30.4%,43.1%), headache (19.6%, 19.0%), tonsillitis (19.6%, 12.1%), pharyngitis (16.1%, 13.8%), acne (14.3%, 8.6%), diarrhoea (12.5%, 12.1%), glomerular filtration rate decreased (12.5%, 6.9%), upper respiratory tract infection (12.5%, 5.2%), psoriasis (12.5%, 1.7%), rhinitis (8.9%, 12.1%), cough (7.1%, 15.5%), pyrexia (7.1%, 10.3%), abdominal pain (7.1%, 10.3%), oropharyngeal pain (7.1%, 10.3%), and bronchitis (5.4%, 10.3%). Noted that AEs were collected from the first dose of study treatment until the last dose of study treatment plus 16 weeks. AEs in any AIN457 arms were collected for a total of 252 weeks, and AEs for the patients who switched from placebo to AIN457 at week 12 were collected for 12 weeks under Placebo arm and up to 240 weeks under AIN457 arms.

Primary endpoint Both AIN457 dose arms (low and high dose) were superior to placebo with respect to PASI 75 response and IGA mod 2011 response of 0 or 1 at Week 12. PASI 75 response rates at Week 12 - AIN457 low dose arm:80.0% (32/40) vs Placebo arm:14.6% (6/41) odds ratio estimate (95% CI): 25.78 (7.08 to 114.66) (p<0.0001). - AIN457 high dose arm:77.5% (31/40) vs Placebo arm:14.6% (6/41) odds ratio estimate (95% CI): 22.65 (6.31 to 98.93) (p<0.0001). IGA mod 2011 response of 0 or1 at Week 12 - AIN457 low dose arm:70.0% (28/40) vs Placebo arm: 5.0% (2/40) odds ratio estimate (95% CI): 51.77 (10.02 to 538.64) (p<0.0001) -AIN457 high dose arm:60.0% (24/40) vs Placebo arm: 5.0% (2/40) odds ratio estimate (95% CI): 32.52 (6.48 to 329.52) (p<0.0001)

Key secondary endpoint Both AIN457 dose arms (low and high dose) were superior to placebo with respect to PASI 90 response at Week 12. PASI 90 response rates at Week 12 - AIN457 low dose arm:72.5% (29/40) vs Placebo arm:2.4% (1/41) odds ratio estimate (95% CI): 72.5 (55.9 to 84.9) (p<0.0001) - AIN457 high dose arm:67.5% (27/40) vs Placebo arm:2.4% (1/41) odds ratio estimate (95% CI): 67.5 (50.8 to 80.9) (p<0.0001) As a supplement, after Week 12, IGA mod 2011 0/1 and the PASI 50/75/90/100 responses were consistently high in both AIN457 dose arms (low and high dose).

The efficacy demonstrated by both AIN457 dose arms (low and high dose) was sustained through the study period. The safety profile of AIN457 in this study in pediatric patients with severe chronic plaque psoriasis showed no new or unexpected safety signals compared to the known safety profile of AIN457.

Feb. 29, 2024

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

July. 06, 2016

Interventional

Randomized, Parallel Assignment, Double Blind Study

treatment purpose

3

*PASI score of 20 or greater at the time of randomization (Wash-out: Other systemic immunomodulating treatments: 4weeks, Phototherapy: 2weeks, Biological immunomodulating agents: 12weeks)

*Current forms of psoriasis other than chronic plaque-type psoriasis (for example, pustular, erythrodermic, guttate) at randomization
*Previous use of secukinumab or any drug that targets IL-17 or IL-17 receptor
Other protocol-defined inclusion/exclusion criteria may apply.

Both

Severe Chronic Pediatric Plaque Psoriasis

Experimental: Secukinumab low dose
Depending on weight group subject will receive per dose a) 75 mg if weighing less than 50 kg b) 150 mg if weighing 50 kg or more. Secukinumab injections (one or two per dose, depending on the weight group) will be administered subcutaneously at Randomization, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48, and Placebo secukinumab at Weeks 13, 14 and 15 during the blinded phase of the study; thereafter at Week 52 and every 4 weeks during the extension treatment period until Week 232.
Experimental: Secukinumab high dose
Depending on weight group subject will receive per dose a) 75 mg if weighing less than 25 kg b) 150 mg if weighing between 25 and less than 50 kg c) 300 mg if weighing more than 50 kg. Secukinumab injections (one or two per dose, depending on the weight group) will be administered subcutaneously at Randomization, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48, and Placebo secukinumab at Weeks 13, 14 and 15 during the blinded phase of the study; thereafter at Week 52 and every 4 weeks during the extension treatment period until Week 232.
Placebo Comparator: Placebo
Placebo secukinumab (one or two subcutaneous injections per dose, depending on weight group) at Randomization and Weeks 1, 2, 3 4 and 8. At Week 12, subjects in the placebo group based on their PASI 75 response status at Week 12 will proceed as follows: - PASI 75 responders will discontinue study treatment at Week 12 and enter the treatment-free follow-up period - PASI 75 non-responders will receive high dose or low dose secukinumab, according to the pre-assignment at the Randomization visit. They will receive their treatment based on the weight category(<25 kg, 25- <50kg, >=50 kg), on Weeks 12, 13, 14, 15, and then every four weeks starting at Week 16 until Week 48 during the maintenance period; thereafter at week 52 and every 4 weeks during the extension treatment period until Week 232.
Active Comparator: Etanercept Comparator
Etanercept 0.8 mg/kg of subject weight and up to a maximum of 50 mg per dose. Subcutaneous etanercept 0.8 mg/kg (one or two injections per dose) once per week, for 51 weeks administered at home (self-injected or by caregiver) or at the study site. At Wk 52 subjects in the etanercept group will move into the treatment-free follow up period and terminate the study.

efficacy
PASI 75 and IGA 0/1

efficacy
PASI 50, 90, 100

+81-52-851-5511

May. 16, 2016