Plaque Psoriasis
Conditions
Brief summary
This study is being conducted to evaluate the efficacy and safety/tolerability of subcutaneous tildrakizumab (MK-3222), followed by an optional long-term safety extension study, in participants with moderate-to-severe chronic plaque psoriasis.
Detailed description
Participants are initially randomized to receive tildrakizumab 200 or 100 mg once weekly at Weeks 0, 4, and every 12 weeks thereafter; or placebo at Weeks 0 and 4. At Week 12, participants initially randomized to placebo will be re-randomized to receive either tildrakizumab 200 or 100 mg at Weeks 12 and 16. At Week 28, all participants enrolled will be assessed for their improvement in PASI score from baseline. RESPONDERS: Participants initially randomized to tildrakizumab who achieve at least a 75% improvement from baseline PASI will be re-randomized to either continue on their initial treatment or to receive placebo at Week 28. * Participants who are re-randomized to continue on their initial treatment will continue tildrakizumab 200 or 100 mg every 12 weeks through Week 64. * Participants who are re-randomized to placebo will receive placebo every 4 weeks until relapse (reduction in maximum PASI response by 50%). If relapse occurs, the tildrakizumab dose that the participants was originally randomized to at baseline will be re-initiated (tildrakizumab 200 or 100 mg). Participants will be dosed tildrakizumab at the visit when the relapse occurs, and subsequent dosing of tildrakizumab will be given 4 weeks after treatment re-initiation, and every 12 weeks thereafter through Week 64. PARTIAL RESPONDERS: Participants initially randomized to tildrakizumab who achieved a PASI response of ≥50% but \<75% improvement from baseline will be assigned a treatment regimen as described below, with their first dose started at Week 28. * Participants initially randomized to tildrakizumab 200 mg will remain on tildrakizumab 200 mg every 12 weeks. * Participants initially randomized to tildrakizumab 100 mg will be re-randomized to either remain on tildrakizumab 100 mg every 12 weeks or to receive tildrakizumab 200 mg every 12 weeks. * Participants initially randomized to placebo who achieved ≥50% improvement from baseline in PASI will receive tildrakizumab (200 or 100 mg) according to their re-randomized treatment assignment at Week 12 and continue on this treatment every 12 weeks through Week 64. NON-RESPONDERS: Participants who did not achieve at least 50% improvement from baseline PASI at Week 28 will be discontinued from the study. EXTENSION: Participants will receive tildrakizumab 200 mg or 100 mg every 12 weeks through Extension Week 192, depending on the treatment received at the time of completion of the base study.
Interventions
Two tildrakizumab 100 mg/mL pre-filled syringes (PFS)
Tildrakizumab 100 mg/mL PFS
DRUGMatching Placebo
Matching placebo to tildrakizumab PFS
Sponsors
Sun Pharmaceutical Industries Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of moderate-to-severe plaque psoriasis for at least 6 months prior to study enrollment * A candidate for phototherapy or systemic therapy * For the extension study: must have completed Part 3 of the base study * For the extension study: must have achieved at least a PASI-50 response by the end of Part 3 of the base study * For the extension study: must have received active tildrakizumab (MK-3222) treatment within 12 weeks prior to the end of Part 3 of the base study * Premenopausal female participants must agree to abstain from heterosexual activity or use a medically accepted method of contraception or use appropriate effective contraception as per local regulations or guidelines * If enrolled at a Japanese site, participants with psoriatic arthritis using non-steroidal anti-inflammatory drugs (NSAIDs) must be on a stable dose for at least 4 weeks prior to the first dose of study drug and must not be expected to require an increase in dose over the course of the study
Exclusion criteria
* Has erythrodermic psoriasis, predominantly pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis * Current or history of severe psoriatic arthritis and is well-controlled on current treatment * Women of child-bearing potential who are pregnant, intend to become pregnant within 6 months of completing the trial, or who are breast feeding * Expected to require topical treatment, phototherapy, or systemic treatment during the trial * Presence of any infection * History of recurrent infection requiring treatment with systemic antibiotics within 2 weeks of screening * Previous use of tildrakizumab (MK-3222) or other IL-23/Th-17 pathway inhibitors including P40, p19, and IL-17 antagonists * Evidence of active or untreated latent tuberculosis (TB) * Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) * At Japanese sites, positive test for HBs antibody and hepatitis B virus (HBV) deoxyribonucleic acid (DNA) * At Japanese sites, positive test for the Hepatitis B core (HBc) antibody and HBV DNA * For the extension study: women of child-bearing potential who are pregnant, intend to become pregnant within 6 months of completing the trial, or who are breast feeding * For the extension study: active or uncontrolled significant organ dysfunction or clinically significant laboratory abnormalities * For the extension study: expected to require topical treatment, phototherapy, or systemic treatment during the extension study * At Japanese sites, abnormal for Beta D Glucan and/or KL-6 test result(s) at the screening visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Discontinuing Study Drug Due to a Drug-Related Adverse Event (Base Study) | Up to 12 weeks | A drug-related adverse event is an adverse event that has been determined by the investigator to be related to the study drug. |
| Percentage of Participants With Psoriasis Area Sensitivity Index 75 (PASI-75) Response at Week 12 (Base Study) | Week 12 (or end of trial if prior to Week 12) | The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% involvement). Calculated PASI score ranges from 0 to 72, with higher score indicating more severe disease status. The PASI-75 response indicates the number of participants achieving a 75% reduction in PASI score compared to baseline. |
| Percentage of Participants With a Physician's Global Assessment (PGA) Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline at Week 12 (Base Study) | Baseline and Week 12 (or end of trial if prior to Week 12) | The PGA is used to determine the overall severity of a participant's psoriasis lesions at a given time point. Overall lesions will be graded for thickness, erythema, and scaling on a scale from 0 to 5. The sum of the 3 scales will be divided by 3 to obtain the PGA score. PGA is assessed as: 0= Cleared, except for residual discoloration. 1= Minimal, majority of lesions have individual scores that average 1. 2 =Mild, majority of lesions have individual scores that average 2. 3= Moderate, majority of lesions have individual scores that average 3. 4= Marked, majority of lesions have individual scores that average 4. 5= Severe, majority of lesions have individual scores that average 5. |
| Number of Participants Experiencing an Adverse Event Up to Week 12 (Base Study) | Up to 12 weeks | An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
| Number of Participants Discontinuing Study Drug Due to an Adverse Event Up to Week 12 (Base Study) | Up to 12 weeks | An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With PASI-90 Response At Week 12 | Week 12 (or end of trial if prior to Week 12) | The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% involvement). Calculated PASI score ranges from 0 to 72, with higher score indicating more severe disease status. The PASI-90 response indicates the number of participants achieving a 90% reduction in PASI score compared to baseline. |
| Percentage of Participants With PASI-100 Response at Week 12 | Week 12 (or end of trial if prior to Week 12) | The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% involvement). Calculated PASI score ranges from 0 to 72, with higher score indicating more severe disease status. The PASI-100 response indicates the number of participants achieving a 100% reduction in PASI score compared to baseline. |
| Baseline Dermatology Life Quality Index (DLQI) Score | Baseline | The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. |
| Change From Baseline in the Participant DLQI Score at Week 12 | Baseline and Week 12 (or end of trial if prior to Week 12) | The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. For a change from baseline, a larger negative number correlates with a greater improvement in the DLQI score. |
| Percentage of Participants With DLQI Score of 0 or 1 at Week 12 | Week 12 (or end of trial if prior to Week 12) | The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. |
Participant flow
Recruitment details
The tables below present the Participant Flow for the Base Study only (Weeks 0 to 64: Part 1 for 12 weeks, Part 2 for 16 weeks, and Part 3 for 36 weeks).
Participants by arm
| Arm | Count |
|---|---|
| Tildrakizumab 200 mg (Part 1) Tildrakizumab 200 mg administered subcutaneously (SC) once a week at Weeks 0 and 4 and then every 12 weeks. | 308 |
| Tildrakizumab 100 mg (Part 1) Tildrakizumab 100 mg administered SC once a week at Weeks 0 and 4 and then every 12 weeks. | 309 |
| Placebo (Part 1) Matching placebo administered SC once a week at Weeks 0 and 4. | 155 |
| Total | 772 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Part 1 | Adverse Event | 5 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1 | Lack of Efficacy | 0 | 0 | 1 | 0 | 2 | 0 | 0 |
| Part 1 | Lost to Follow-up | 1 | 0 | 2 | 0 | 1 | 0 | 0 |
| Part 1 | Physician Decision | 0 | 0 | 3 | 0 | 1 | 0 | 0 |
| Part 1 | Pregnancy | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1 | Progressive Disease | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Part 1 | Protocol Violation | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| Part 1 | Withdrawal by Subject | 2 | 0 | 3 | 0 | 3 | 0 | 0 |
| Part 2 | Adverse Event | 3 | 0 | 0 | 0 | 0 | 1 | 0 |
| Part 2 | Lack of Efficacy | 3 | 0 | 11 | 0 | 0 | 3 | 3 |
| Part 2 | Lost to Follow-up | 0 | 0 | 3 | 0 | 0 | 1 | 1 |
| Part 2 | Non-Compliance with Study Drug | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| Part 2 | Other Protocol Specified Criteria | 6 | 0 | 10 | 0 | 0 | 2 | 1 |
| Part 2 | Physician Decision | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| Part 2 | Pregnancy | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Part 2 | Progressive Disease | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Part 2 | Protocol Violation | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 2 | Withdrawal by Subject | 5 | 0 | 3 | 0 | 0 | 2 | 2 |
| Part 3 | Adverse Event | 2 | 2 | 0 | 1 | 0 | 0 | 0 |
| Part 3 | Death | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 3 | Lack of Efficacy | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 3 | Lost to Follow-up | 3 | 4 | 0 | 0 | 0 | 1 | 0 |
| Part 3 | Non-Compliance with Study Drug | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part 3 | Other Protocol Specified Criteria | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part 3 | Physician Decision | 1 | 1 | 0 | 0 | 0 | 0 | 1 |
| Part 3 | Protocol Violation | 2 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part 3 | Withdrawal by Subject | 4 | 7 | 0 | 0 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Tildrakizumab 200 mg (Part 1) | Tildrakizumab 100 mg (Part 1) | Placebo (Part 1) | Total |
|---|---|---|---|---|
| Age, Continuous | 46.9 Years STANDARD_DEVIATION 13.16 | 46.4 Years STANDARD_DEVIATION 13.09 | 47.9 Years STANDARD_DEVIATION 13.55 | 46.9 Years STANDARD_DEVIATION 13.21 |
| Body weight <=90 kg | 182 Participants | 183 Participants | 93 Participants | 458 Participants |
| Body weight >90 kg | 126 Participants | 126 Participants | 62 Participants | 314 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 37 Participants | 34 Participants | 19 Participants | 90 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 271 Participants | 275 Participants | 135 Participants | 681 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Physician's Global Assessment (PGA) score 3 | 202 Participants | 206 Participants | 111 Participants | 519 Participants |
| Physician's Global Assessment (PGA) score <3 | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Physician's Global Assessment (PGA) score 4 | 95 Participants | 95 Participants | 41 Participants | 231 Participants |
| Physician's Global Assessment (PGA) score 5 | 11 Participants | 7 Participants | 2 Participants | 20 Participants |
| Prior exposure to biologics therapy for psoriasis No | 237 Participants | 238 Participants | 120 Participants | 595 Participants |
| Prior exposure to biologics therapy for psoriasis Yes | 71 Participants | 71 Participants | 35 Participants | 177 Participants |
| Sex: Female, Male Female | 82 Participants | 102 Participants | 55 Participants | 239 Participants |
| Sex: Female, Male Male | 226 Participants | 207 Participants | 100 Participants | 533 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 308 | 0 / 309 | 0 / 155 | 0 / 298 | 0 / 299 | 0 / 279 | 1 / 19 |
| other Total, other adverse events | 35 / 308 | 36 / 309 | 23 / 154 | 38 / 370 | 42 / 374 | 86 / 360 | 78 / 316 |
| serious Total, serious adverse events | 8 / 308 | 5 / 309 | 1 / 154 | 8 / 370 | 7 / 374 | 21 / 360 | 14 / 316 |
Outcome results
Primary
Number of Participants Discontinuing Study Drug Due to a Drug-Related Adverse Event (Base Study)
A drug-related adverse event is an adverse event that has been determined by the investigator to be related to the study drug.
Time frame: Up to 12 weeks
Population: Analysis population included all randomized participants who received at least 1 dose of study medication during Weeks 0 to 12 based on the treatment actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tildrakizumab 200 mg (Part 1) | Number of Participants Discontinuing Study Drug Due to a Drug-Related Adverse Event (Base Study) | 2 Participants |
| Tildrakizumab 100 mg (Part 1) | Number of Participants Discontinuing Study Drug Due to a Drug-Related Adverse Event (Base Study) | 0 Participants |
| Placebo (Part 1) | Number of Participants Discontinuing Study Drug Due to a Drug-Related Adverse Event (Base Study) | 0 Participants |
Primary
Number of Participants Discontinuing Study Drug Due to an Adverse Event Up to Week 12 (Base Study)
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to 12 weeks
Population: Analysis population included all randomized participants who received at least 1 dose of study medication during Weeks 0 to 12 based on the treatment actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tildrakizumab 200 mg (Part 1) | Number of Participants Discontinuing Study Drug Due to an Adverse Event Up to Week 12 (Base Study) | 5 Participants |
| Tildrakizumab 100 mg (Part 1) | Number of Participants Discontinuing Study Drug Due to an Adverse Event Up to Week 12 (Base Study) | 0 Participants |
| Placebo (Part 1) | Number of Participants Discontinuing Study Drug Due to an Adverse Event Up to Week 12 (Base Study) | 1 Participants |
Primary
Number of Participants Experiencing an Adverse Event Up to Week 12 (Base Study)
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to 12 weeks
Population: Analysis population included all randomized participants who received at least 1 dose of study medication during Weeks 0 to 12 based on the treatment actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tildrakizumab 200 mg (Part 1) | Number of Participants Experiencing an Adverse Event Up to Week 12 (Base Study) | 130 Participants |
| Tildrakizumab 100 mg (Part 1) | Number of Participants Experiencing an Adverse Event Up to Week 12 (Base Study) | 146 Participants |
| Placebo (Part 1) | Number of Participants Experiencing an Adverse Event Up to Week 12 (Base Study) | 74 Participants |
Primary
Percentage of Participants With a Physician's Global Assessment (PGA) Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline at Week 12 (Base Study)
The PGA is used to determine the overall severity of a participant's psoriasis lesions at a given time point. Overall lesions will be graded for thickness, erythema, and scaling on a scale from 0 to 5. The sum of the 3 scales will be divided by 3 to obtain the PGA score. PGA is assessed as: 0= Cleared, except for residual discoloration. 1= Minimal, majority of lesions have individual scores that average 1. 2 =Mild, majority of lesions have individual scores that average 2. 3= Moderate, majority of lesions have individual scores that average 3. 4= Marked, majority of lesions have individual scores that average 4. 5= Severe, majority of lesions have individual scores that average 5.
Time frame: Baseline and Week 12 (or end of trial if prior to Week 12)
Population: Analysis population consists of all randomized participants who received at least one dose of assigned study drug between Weeks 0 and 12.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tildrakizumab 200 mg (Part 1) | Percentage of Participants With a Physician's Global Assessment (PGA) Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline at Week 12 (Base Study) | 59.1 Percentage of Participants |
| Tildrakizumab 100 mg (Part 1) | Percentage of Participants With a Physician's Global Assessment (PGA) Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline at Week 12 (Base Study) | 57.9 Percentage of Participants |
| Placebo (Part 1) | Percentage of Participants With a Physician's Global Assessment (PGA) Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline at Week 12 (Base Study) | 7.1 Percentage of Participants |
p-value: <0.00195% CI: [44.8, 58.5]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [43.6, 57.4]Cochran-Mantel-Haenszel
Primary
Percentage of Participants With Psoriasis Area Sensitivity Index 75 (PASI-75) Response at Week 12 (Base Study)
The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% involvement). Calculated PASI score ranges from 0 to 72, with higher score indicating more severe disease status. The PASI-75 response indicates the number of participants achieving a 75% reduction in PASI score compared to baseline.
Time frame: Week 12 (or end of trial if prior to Week 12)
Population: Analysis population consists of all randomized participants who received at least one dose of assigned study drug between Weeks 0 and 12.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tildrakizumab 200 mg (Part 1) | Percentage of Participants With Psoriasis Area Sensitivity Index 75 (PASI-75) Response at Week 12 (Base Study) | 62.3 Percentage of Participants |
| Tildrakizumab 100 mg (Part 1) | Percentage of Participants With Psoriasis Area Sensitivity Index 75 (PASI-75) Response at Week 12 (Base Study) | 63.8 Percentage of Participants |
| Placebo (Part 1) | Percentage of Participants With Psoriasis Area Sensitivity Index 75 (PASI-75) Response at Week 12 (Base Study) | 5.8 Percentage of Participants |
p-value: <0.00195% CI: [49.6, 62.8]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [51, 64.1]Cochran-Mantel-Haenszel
Secondary
Baseline Dermatology Life Quality Index (DLQI) Score
The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life.
Time frame: Baseline
Population: Analysis population consists of all randomized participants who received at least one dose of assigned study drug between Weeks 0 and 12 and have baseline DLQI measurement
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tildrakizumab 200 mg (Part 1) | Baseline Dermatology Life Quality Index (DLQI) Score | 13.2 Score on a scale | Standard Deviation 6.87 |
| Tildrakizumab 100 mg (Part 1) | Baseline Dermatology Life Quality Index (DLQI) Score | 13.9 Score on a scale | Standard Deviation 6.68 |
| Placebo (Part 1) | Baseline Dermatology Life Quality Index (DLQI) Score | 13.2 Score on a scale | Standard Deviation 7.25 |
Secondary
Change From Baseline in the Participant DLQI Score at Week 12
The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. For a change from baseline, a larger negative number correlates with a greater improvement in the DLQI score.
Time frame: Baseline and Week 12 (or end of trial if prior to Week 12)
Population: Analysis population consists of all randomized participants who received at least one dose of assigned study drug between Weeks 0 and 12 and have at least one DLQI measurement (post-baseline or baseline).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Tildrakizumab 200 mg (Part 1) | Change From Baseline in the Participant DLQI Score at Week 12 | -10.0 Score on a scale |
| Tildrakizumab 100 mg (Part 1) | Change From Baseline in the Participant DLQI Score at Week 12 | -9.8 Score on a scale |
| Placebo (Part 1) | Change From Baseline in the Participant DLQI Score at Week 12 | -2.3 Score on a scale |
p-value: <0.00195% CI: [-8.6, -6.8]Constrained Longitudinal Data Analysis
p-value: <0.00195% CI: [-8.3, -6.5]Constrained Longitudinal Data Analysis
Secondary
Percentage of Participants With DLQI Score of 0 or 1 at Week 12
The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life.
Time frame: Week 12 (or end of trial if prior to Week 12)
Population: Analysis population consists of all randomized participants who received at least one dose of assigned study drug between Weeks 0 and 12 and have a DLQI measurement at Week 12 (or end of trial if prior to Week 12).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tildrakizumab 200 mg (Part 1) | Percentage of Participants With DLQI Score of 0 or 1 at Week 12 | 44.2 Percentage of participants |
| Tildrakizumab 100 mg (Part 1) | Percentage of Participants With DLQI Score of 0 or 1 at Week 12 | 41.5 Percentage of participants |
| Placebo (Part 1) | Percentage of Participants With DLQI Score of 0 or 1 at Week 12 | 5.3 Percentage of participants |
p-value: <0.00195% CI: [31.9, 45.4]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [29.3, 42.5]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With PASI-100 Response at Week 12
The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% involvement). Calculated PASI score ranges from 0 to 72, with higher score indicating more severe disease status. The PASI-100 response indicates the number of participants achieving a 100% reduction in PASI score compared to baseline.
Time frame: Week 12 (or end of trial if prior to Week 12)
Population: Analysis population consists of all randomized participants who received at least one dose of assigned study drug between Weeks 0 and 12.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tildrakizumab 200 mg (Part 1) | Percentage of Participants With PASI-100 Response at Week 12 | 14.0 Percentage of participants |
| Tildrakizumab 100 mg (Part 1) | Percentage of Participants With PASI-100 Response at Week 12 | 13.9 Percentage of participants |
| Placebo (Part 1) | Percentage of Participants With PASI-100 Response at Week 12 | 1.3 Percentage of participants |
p-value: <0.00195% CI: [8.3, 17.2]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [8, 17.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With PASI-90 Response At Week 12
The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% involvement). Calculated PASI score ranges from 0 to 72, with higher score indicating more severe disease status. The PASI-90 response indicates the number of participants achieving a 90% reduction in PASI score compared to baseline.
Time frame: Week 12 (or end of trial if prior to Week 12)
Population: Analysis population consists of all randomized participants who received at least one dose of assigned study drug between Weeks 0 and 12.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tildrakizumab 200 mg (Part 1) | Percentage of Participants With PASI-90 Response At Week 12 | 35.4 Percentage of participants |
| Tildrakizumab 100 mg (Part 1) | Percentage of Participants With PASI-90 Response At Week 12 | 34.6 Percentage of participants |
| Placebo (Part 1) | Percentage of Participants With PASI-90 Response At Week 12 | 2.6 Percentage of participants |
p-value: <0.00195% CI: [26.8, 38.8]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [25.9, 38]Cochran-Mantel-Haenszel