Chronic Plaque Psoriasis, Moderate to Severe Nail Psoriasis
Conditions
Brief summary
Phase 3b study to Assess the Efficacy and Safety of Tildrakizumab in the Treatment of Moderate to Severe Nail Psoriasis
Interventions
DRUGTildrakizumab
PART 1: Double-blind Placebo-controlled PART 2: Double-blind Active Treatment Extension PART 3: Observational Safety Follow-up
DRUGPlacebo
PART 1: Double-blind Placebo-controlled PART 2: Double-blind Active Treatment Extension PART 3: Observational Safety Follow-up
Sponsors
Sun Pharmaceutical Industries Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects are eligible to be included in the study only if all of the following criteria apply: 1. Subjects with a chronic moderate to severe plaque-type psoriasis for at least 6 months (as determined by subject interview and confirmation of diagnosis through physical examination by Investigator). 2. Subjects must have moderate to severe nail psoriasis at Screening and Baseline, defined by: * mNAPSI score of ≥20. * ViSENPsO ≥3 3. Subjects must have moderate to severe plaque psoriasis at Screening and Baseline, defined by: * s-PGA score of at least 3. * Body Surface Area (BSA) involvement of ≥10%. * PASI ≥12 4. Subjects must be considered candidates for systemic therapy, meaning psoriasis inadequately controlled by topical treatments (corticosteroids), and/or phototherapy, and/or previous systemic therapy.
Exclusion criteria
Subjects are excluded from the study if any of the following criteria apply: 1. Subjects who have predominantly non-plaque forms of psoriasis, specifically erythrodermic psoriasis, predominantly pustular psoriasis, medication-induced, or medication-exacerbated psoriasis, or new-onset guttate psoriasis. 2. Subjects with ongoing inflammatory skin diseases other than psoriasis or any other disease affecting the fingernails, which may potentially confound the evaluation of study treatment. 3. Subjects with fungal nail infection should be excluded from the study. Subjects in whom the Investigator suspects a fungal nail infection in addition to nail psoriasis should have scrapings sent for direct microscopy and fungal culture. If fungal culture or direct microscopy of nail scrapings turns out to be positive for fungal infection, the subject should be excluded from the study. At the discretion of the investigator, Periodic Acid-Schiff (PAS) staining for nail clippings could also be considered to rule of fungal infection of the nails. Direct microscopy or fungal culture are not required if fungal infection is diagnosed in PAS staining. 4. Subjects with any previous use of tildrakizumab or other IL-23/Th-17 pathway inhibitors, including p40, p19 and IL-17 antagonists for psoriasis. 5. Subjects with known history of allergy or hypersensitivity to any of the inactive ingredients of the Tildrakizumab or placebo formulations.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Subjects Who Achieve at Least a 75% Improvement From Baseline in Total mNAPSI at Week 28. | Week 28 | Primary Efficacy Endpoint |
Secondary
| Measure | Time frame |
|---|---|
| The Proportion of Subjects With a Score of "0 - Normal" or "1 - Minimal Nail Psoriasis" and at Least a 2-point Decrease From Baseline at Week 28 as Measured by the ViSENPsO. | Week 28 |
| The Proportion of Subjects With at Least 3 Point Decrease From Baseline, in Nail Pain NRS Score in Subjects With Baseline Nail Pain NRS Score of >3 | Week 28 |
Countries
Australia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Subjects received placebo up to Week 28 | 48 |
| Tildrakizumab 100 mg Subjects received Tildrakizumab 100 mg upto week 16. | 51 |
| Total | 99 |
Baseline characteristics
| Characteristic | Placebo | Tildrakizumab 100 mg | Total |
|---|---|---|---|
| Age, Continuous | 46.2 years STANDARD_DEVIATION 15.14 | 46.6 years STANDARD_DEVIATION 11.74 | 46.4 years STANDARD_DEVIATION 13.43 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 18 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 33 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 16 Participants | 13 Participants | 29 Participants |
| Sex: Female, Male Male | 32 Participants | 38 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 48 |
| other Total, other adverse events | 28 / 51 | 19 / 48 |
| serious Total, serious adverse events | 3 / 51 | 2 / 48 |
Outcome results
Primary
The Proportion of Subjects Who Achieve at Least a 75% Improvement From Baseline in Total mNAPSI at Week 28.
Primary Efficacy Endpoint
Time frame: Week 28
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | The Proportion of Subjects Who Achieve at Least a 75% Improvement From Baseline in Total mNAPSI at Week 28. | 0.042 proportion of subjects |
| Tildrakizumab 100 mg | The Proportion of Subjects Who Achieve at Least a 75% Improvement From Baseline in Total mNAPSI at Week 28. | 0.255 proportion of subjects |
p-value: 0.00311Cochran-Mantel-Haenszel
Secondary
The Proportion of Subjects With a Score of 0 - Normal or 1 - Minimal Nail Psoriasis and at Least a 2-point Decrease From Baseline at Week 28 as Measured by the ViSENPsO.
Time frame: Week 28
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | The Proportion of Subjects With a Score of 0 - Normal or 1 - Minimal Nail Psoriasis and at Least a 2-point Decrease From Baseline at Week 28 as Measured by the ViSENPsO. | 0.042 Proportion of subjects |
| Tildrakizumab 100 mg | The Proportion of Subjects With a Score of 0 - Normal or 1 - Minimal Nail Psoriasis and at Least a 2-point Decrease From Baseline at Week 28 as Measured by the ViSENPsO. | 0.294 Proportion of subjects |
p-value: 0.00079Cochran-Mantel-Haenszel
Secondary
The Proportion of Subjects With at Least 3 Point Decrease From Baseline, in Nail Pain NRS Score in Subjects With Baseline Nail Pain NRS Score of >3
Time frame: Week 28
Population: The number of subjects analysed represents the Intent-to-Treat population with baseline nail pain NRS ≥ 3
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | The Proportion of Subjects With at Least 3 Point Decrease From Baseline, in Nail Pain NRS Score in Subjects With Baseline Nail Pain NRS Score of >3 | 0.257 proportion of subjects |
| Tildrakizumab 100 mg | The Proportion of Subjects With at Least 3 Point Decrease From Baseline, in Nail Pain NRS Score in Subjects With Baseline Nail Pain NRS Score of >3 | 0.455 proportion of subjects |
p-value: 0.09892Cochran-Mantel-Haenszel
Other Pre-specified
The Percentage of Subjects With Incidence, Seriousness, and Severity of All Adverse Events.
Primary Safety Endpoint
Time frame: Week 52
Other Pre-specified
The Percentage of Subjects With Injection Site Reactions (eg. Pain, Erythema, Edema Etc)
Primary Safety Endpoint
Time frame: Week 52
Other Pre-specified
The Percentage of Subjects With Major Adverse Cardiovascular Events.
Primary Safety Endpoint
Time frame: Week 52
Other Pre-specified
The Percentage of Subjects With Malignancies (Excluding Carcinoma in Situ of the Cervix).
Primary Safety Endpoint
Time frame: Week 52
Other Pre-specified
The Percentage of Subjects With Melanoma Skin Cancer.
Primary Safety Endpoint
Time frame: Week 52
Other Pre-specified
The Percentage of Subjects With Non-melanoma Skin Cancer.
Primary Safety Endpoint
Time frame: Week 52
Other Pre-specified
The Percentage of Subjects With Severe Infections Whether or Not Reported as a Serious Event Defined as Any Infection Meeting the Regulatory Definition of a Serious Adverse Event, or Any Infection Requiring Intravenous Antibiotics.
Primary Safety Endpoint
Time frame: Week 52
Other Pre-specified
The Percentage of Subjects With Study Treatment Related Hypersensitivity Reactions (eg, Anaphylaxis, Urticaria, Angioedema, Etc).
Primary Safety Endpoint
Time frame: Week 52