Chronic Plaque-type Psoriasis
Conditions
Keywords
Psoriasis, Plaque psoriasis, Secukinumab, Skin condition, skin disease, itching, psoriasis vulgaris, immune-mediated systemic disease, skin lesions, scaly patches, papules
Brief summary
The aim of this study was to describe the effect of direct IL-17A inhibition with secukinumab as compared with the selective inhibition of IL-23 with guselkumab (p19 subunit blocker) in controlling inflammation in psoriatic plaques that remain active despite treatment with the non-selective IL-23 inhibitor ustekinumab (blocker of p40 subunit, shared by IL-12 and IL 23).
Detailed description
This was a 16-week, randomized, open-label, parallel-group, active-control, Phase 2a study comparing secukinumab 300 mg s.c. versus guselkumab 100 mg s.c. in subjects with plaque psoriasis who had an inadequate response to ustekinumab. Forty subjects will be randomized 1:1 and treated for 16 weeks. In each patient, a target active refractory skin plaque (TCS ≥6) is described and biopsied at baseline and at study end. The objective of the study was to assess the superiority of secukinumab over guselkumab in achieving clear/almost clear status (TCS 0-2) of the target plaques; and to describe the molecular mechanisms behind this difference
Interventions
PROCEDURESkin biopsies
At Baseline, two 6-mm punch biopsies were taken, one from the identified active plaque (TCS ≥ 6) and one from never-lesional skin. At the End-of-study Visit, one biopsy was taken from the same area of the active plaque sampled at Baseline.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Blinded outcome assessor assessed subjects on each visit for target plaque TCS, PASI, IGA, BSA, ppIGA, PSSI, NAPS.
Intervention model description
This was a 16-week, randomized, open-label, parallel-group, active-control study comparing secukinumab 300 mg s.c. versus guselkumab 100 mg s.c. in subjects with plaque psoriasis who had an inadequate response to ustekinumab.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Chronic plaque-type psoriasis considered inadequately controlled after treatment with ustekinumab according to the following criteria-: * Ustekinumab administered at a dose equal or higher than that on the label for at least 24 weeks. The last administration must be at least 12 weeks before randomization * absolute PASI score of 1-10 at Screening * Presence of at least 1 refractory skin plaque, defined by a TCS of at least 6 and severity score of at least 2 or 3 (moderate) for each individual item, with an area ≥ 10 cm2 at screening.
Exclusion criteria
* Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and guttate psoriasis) at Screening or Baseline * Drug-induced psoriasis (i.e., new onset or current exacerbation from beta-blockers, calcium channel inhibitors or lithium) at Baseline * Previous treatment with more than one TNFα inhibitor or with IL-17A (including secukinumab), IL-17R or IL-23 (including guselkumab) inhibitors * Use of other investigational drugs within 4 weeks before enrolment, or within a period of 5 half lives of enrollment/initiation of the study treatment, whichever is longer * Ongoing use of prohibited treatments (see Section 6.2.2) * Known immunosuppression (e.g., AIDS) at Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Whose Plaque Achieves Clear or Almost Clear Status (TCS = 0-2) | 16 week | Total clinical score: number (%) of subjects who responded at Week 16 (FAS) |
Countries
Canada, Germany, United States
Participant flow
Recruitment details
The Screening Phase was completed by 40 (95.2%) of the 42 subjects screened. One (2.4%) subject was rescreened and 2 (4.8%) subjects failed screening
Pre-assignment details
39 (97.5%) subjects completed this trial
Participants by arm
| Arm | Count |
|---|---|
| Secukinumab 20 subjects with plaque psoriasis with an inadequate response to ustekinumab self-administered 300 mg secukinumab as two 150-mg s.c. injections at Baseline, Weeks 1, 2, 3, 4 and then every 4 weeks until Week 12 inclusive | 20 |
| Guselkumab 20 subjects with plaque psoriasis with an inadequate response to ustekinumab self-administered guselkumab as 100 mg s.c. injections at Baseline, Weeks 4, and 12. | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | Secukinumab | Guselkumab | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 1 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 19 Participants | 36 Participants |
| Age, Continuous | 47.6 Years STANDARD_DEVIATION 15.1 | 48.5 Years STANDARD_DEVIATION 12.3 | 48.1 Years STANDARD_DEVIATION 13.6 |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 17 Participants | 20 Participants | 37 Participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Male | 14 Participants | 15 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 11 / 20 | 5 / 20 |
| serious Total, serious adverse events | 2 / 20 | 1 / 20 |
Outcome results
Primary
Proportion of Subjects Whose Plaque Achieves Clear or Almost Clear Status (TCS = 0-2)
Total clinical score: number (%) of subjects who responded at Week 16 (FAS)
Time frame: 16 week
Population: The Full Analysis Set (FAS) comprised all subjects to whom study treatment had been assigned by randomization. According to the intent-to-treat principle, subjects were analyzed according to the treatment they were assigned to during the randomization procedure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Secukinumab | Proportion of Subjects Whose Plaque Achieves Clear or Almost Clear Status (TCS = 0-2) | 12 Participants |
| Guselkumab | Proportion of Subjects Whose Plaque Achieves Clear or Almost Clear Status (TCS = 0-2) | 8 Participants |
Comparison: Proportion of subjects whose plaque achieves clear or almost clear status (TCS = 0-2)p-value: 0.171595% CI: [-13.3, 50.3]Fisher Exact