| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate to Severe Plaque Psoriasis |
|
| E.1.1.1 | Medical condition in easily understood language |
| Moderate to Severe Plaque Psoriasis |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10071117 |
| E.1.2 | Term | Plaque psoriasis |
| E.1.2 | System Organ Class | 100000004858 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Part A: Pharmacokinetics: to evaluate the PK at steady-state of deucravacitinib in subjects in Cohort 1 (age 12 to <18 years) and Cohort 2 (age 4 to <12 years) with moderate to severe plaque psoriasis
Part B: Efficacy: to evaluate the efficacy of the standard dose of deucravacitinib vs placebo in subjects in Cohort 1 (age 12 to <18 years)
and Cohort 2 (age 4 to <12 years) with moderate to severe plaque psoriasis
LTE Period: Safety: to characterize the safety/tolerability of deucravacitinib in pediatric subjects with moderate to severe plaque psoriasis |
|
| E.2.2 | Secondary objectives of the trial |
Part A: Safety: to evaluate the safety/tolerability of deucravacitinib in subjects in Cohort 1 (age 12 to < 18 years) and Cohort 2 (age 4 to <12 years) with moderate to severe plaque psoriasis
Part B: Efficacy: to assess the efficacy in additional endpoints of deucravacitinib vs placebo in subjects in Cohort 1 (age 12 to <18 years) and Cohort 2 (age 4 to <12 years) with moderate to severe plaque psoriasis
LTE Period: Efficacy: to characterize the maintenance of response to 2 dose levels of deucravacitinib in the treatment of pediatric subjects with moderate to severe plaque psoriasis |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Male and females aged 12 to < 18 years for Cohort 1 and aged 4 to <12 years for Cohort 2.
- diagnosed with stable (defined as no significant flares of disease activity or morphologic changes for 6 months) moderate to severe plaque psoriasis. Moderate to severe psoriasis defined by: (at screening visit and Day 1) Psoriasis Area and Severity Index (PASI) ≥ 12, // static Physician’s Global Assessment (sPGA) ≥ 3, // Body Surface Area (BSA) ≥ 10% involvement
- candidates for phototherapy or systemic therapy
LTE Period:
- Subjects must be willing to participate in the optional LTE period and must have the ability to sign the ICF.
- Subjects must have completed the Week 52 treatment period in Part A or B of the study. |
|
| E.4 | Principal exclusion criteria |
1. Subject has non-plaque forms of psoriasis (e.g. erythrodermic, guttate, inverse or pustular)
2. Subjects weighing < 30 Kg at screening
3. Subject has any of the following TB criteria:
a) History of active TB prior to screening visit, regardless of completion of adequate treatment
b) Signs or symptoms of active TB during screening as judged by the investigator
c) A chest x-ray showing evidence of current active or old active pulmonary TB
d) Latent TB infection (LTBI) defined as positive IGRA (QuantiFERON-TB Gold) at screening
4. Received live vaccine within 60 days or plan to receive a live vaccine during the study or plan to receive live vaccine within 60 days of last dose of study medication
5. Currently being treated with biologic agents
6. History of ongoing, chronic or recurrent infectious disease, and opportunistic infection regardless of successfully treatment
LTE Period:
a) Any disease or medical condition that, in the opinion of the investigator, would make the subject unsuitable for this treatment period, would interfere with the interpretation of subject safety or study results, or is considered unsuitable by the investigator for any other reason
b) Prior permanent discontinuation of study treatment in Part A or B of the study c) Evidence of active TB (see Section 9.4.4)
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
PART A:
1. Geometric mean observed average concentration at steady state (Cavg.ss), maximum observed plasma concentration at steady state (Cmax), and trough observed plasma concentration (Ctrough) for deucravacitinib.
PART B:
1. Proportion of subjects with at least 75% improvement in Psoriasis Area and Severity Index (PASI 75)
2. Proportion of subjects with an sPGA score of 0 (clear) or 1 (almost clear) with at least a 2-point reduction from baseline
LTE Period:
1. AEs and SAEs
2. Monitoring of growth including body weight and height and sexual maturation
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part A
1. Week 2
Part B
1. Week 16
2. Week 16
LTE Period:
1. and 2. throughout the study |
|
| E.5.2 | Secondary end point(s) |
Part A:
1. AEs, SAEs, laboratory parameters, lymphocyte subsets and function, cytokine levels, physical examination and vital signs throughout the study
2. Monitoring of growth including body weight and height, and sexual maturation
Part B:
1. Proportion of subjects with at least 75% improvement in PASI (PASI 75) for the comparison of the half-standard dose of deucravacitinib vs placebo
2. Proportion of subjects with an sPGA score of 0 (clear) or 1 (almost clear) with at least a 2-point reduction from baseline for the comparison of the half-standard dose of BMS-986165 vs placebo
3. Proportion of subjects with at least 90% improvement in PASI (PASI 90)
4. Change from baseline in PASI
5. Change from baseline in BSA involvement
6. Change from baseline in CDLQI score
7. Change from baseline in subject reported visual analog scale (VAS) for subject’s assessment of joint pain (only for subjects with confirmed JPsA prior to baseline)
8. Change from baseline in VAS for subject’s Global Assessment of Joint Disease (only for subjects with confirmed JPsA prior to baseline)
9. Proportion of subjects achieving American College ofRheumatology Pediatric 30 (ACR Pedi 30) response for subjects with confirmed JPsA prior to baseline. ACR Pedi 30 response is defined as subjects with at least 30% improvement from baseline in 3 of any 6 variables in the core set, while no more than one of the remaining variables can worsen by > 30%
10. Proportion of subjects using topical corticosteroid
11. AEs, SAEs, laboratory parameters, lymphocyte subsets and function, cytokine levels, physical examination and vital signs
12. Proportion of subjects with protective titers of antibodies to measles, tetanus and pertussis
13. Monitoring of growth including body weight and height, and sexual maturation
14. Geometric mean observed Cavg.ss, Cmax.ss, and Ctrough at steady state for deucravacitinib
LTE Period:
1. Proportion of subjects with 75% improvement in PASI (PASI 75) over time
2. Proportion of subjects with an sPGA score of 0 (clear) or 1 (almost clear) with at least a 2-point reduction |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Part A:
1. and 2. Throughout the study
Part B:
1. to 10. at Week 16
11. throughout the study
12. at Week 16
13. throughout the study
14. at Week 16
LTE Period:
1. and 2. Throughout the study |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 23 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Canada |
| Japan |
| United States |
| France |
| Poland |
| Spain |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 10 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 30 |
| E.8.9.2 | In all countries concerned by the trial years | 10 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 4 |
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