Psoriasis
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled, multicenter study designed to assess the safety and efficacy of PPC-06 (tepilamide fumarate) extended release in subjects with moderate-to-severe plaque psoriasis.
Detailed description
This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter study designed to assess the safety and efficacy of PPC-06 in subjects with moderate-to-severe plaque psoriasis. Study subjects will be enrolled at approximately 75 sites in the United States (US). Approximately 400 subjects who meet the study entry criteria will be randomly assigned in a 1:1:1:1 ratio to 1 of the 4 treatment arms: 1. PPC-06 400 mg once daily (QD) 2. PPC-06 400 mg BID 3. PPC-06 600 mg BID 4. Placebo BID The maximum study duration for each subject will be approximately 29 weeks.
Interventions
DRUGPPC-06 400 mg QD
Tepilamide Fumarate 400 mg tablet once per day
DRUGPPC-06 400 mg BID
Tepilamide Fumarate tablets 400 mg twice per day
DRUGPPC-06 600 mg
Tepilamide Fumarate tablets 600 mg twice per day
DRUGPlacebo
white tablet with no active ingredient manufactured to mimic Tepilamide Fumarate tablets
Sponsors
Dr. Reddy's Laboratories Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Generally healthy males or non-pregnant females age ≥18 years at the time of screening (or who have reached the state minimum legal age of consent). * Stable, moderate-to-severe plaque psoriasis diagnosed for at least 6 months prior to randomization (no morphology changes or significant flares of disease activity in the last 6 months in the opinion of the investigator or as reported by the subject). * Severity of disease meeting all 3 of the following criteria prior to randomization (at the Baseline \[Day 0\] visit): 1. PASI score of ≥12 2. Total body surface area (BSA) affected by plaque psoriasis of ≥10% 3. IGA score of \>3 * Must be a candidate for phototherapy and/or systemic therapy for psoriasis.
Exclusion criteria
* Subjects with non-plaque psoriasis (ie, predominantly inverse, erythrodermic, predominantly guttate, or pustular psoriasis). * Subjects with drug-induced psoriasis or subjects with drug-exacerbated psoriasis that has not resolved within 4 weeks prior to screening. * Subjects who have received systemic non-biologic psoriasis therapy or phototherapy (including either oral and topical psoralen and ultraviolet A (PUVA) light therapy, ultraviolet B, or self-treatment with tanning beds or therapeutic sunbathing) within 4 weeks prior to the Baseline Visit. * Subjects who had topical psoriasis treatment within the previous 2 weeks prior to the Baseline Visit. * Subjects with history of concurrent or recent use of any biologic agent within the following washout periods prior to baseline visit: * Etanercept - 35 days * Infliximab, adalimumab - 12 weeks * Ustekinumab - 24 weeks * Any other biologic agent \<5 half-lives prior to the Baseline Visit * Subjects with history of use of any investigational drug within 28 days prior to randomization, or 5 pharmacokinetic/ pharmacodynamic half-lives (whichever is longer).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Achieving Psoriasis Area and Severity Index (PASI) - 75 at the End of Week 24 | End of Week 24 | The percentage of subjects who achieve a reduction of 75% or greater from Baseline in the Psoriasis Area and Severity Index (PASI-75) The PASI is a measure of the average redness, thickness, and scaliness of the lesions (each graded on a 0-4 scale) and is weighted by the area of involvement. The minimum possible score on this scale is '0', while the maximum score on this scale is 72. A lower score on this scale at the end of the study indicates an improvement in the condition of subject. |
| Achieving the Investigator's Global Assessment (IGA) Score of 0 or 1 | End of Week 24 | The Percentage of subjects who achieve the Investigator's Global Assessment (IGA) score of clear or almost clear (IGA score 0 or 1) Score Grade Definition 0 Clear: No signs of psoriasis 1. Almost clear: No thickening to minimal plaque elevation; Normal to slight pink coloration/faint erythema; Focal to minimal scaling 2. Mild: Slight elevation/thickening; Pink to light red coloration; Predominantly fine scaling partially or mostly covering lesions 3. Moderate: Clearly distinguishable/distinct thickening; Definite red coloration; Coarse scaling covering most plaques 4. Severe: Marked thickening with hard/sharp edges; Bright to deep dark red coloration; Thick/coarse scaling covering almost all or all lesions A lower score on this scale at the end of the study indicates an improvement in the disease condition. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PPC-06 400 mg QD Tepilamide Fumarate 400 mg once per day
PPC-06 400 mg QD: Tepilamide Fumarate 400 mg tablet once per day | 105 |
| PPC-06 400 mg BID Tepilamide Fumarate 400 mg twice per day
PPC-06 400 mg BID: Tepilamide Fumarate tablets 400 mg twice per day | 107 |
| PPC-06 600 mg BID Tepilamide Fumarate 600 mg twice per day
PPC-06 600 mg: Tepilamide Fumarate tablets 600 mg twice per day | 107 |
| Placebo BID White placebo tablet to mimic Tepilamide Fumarate
Placebo: white tablet with no active ingredient manufactured to mimic Tepilamide Fumarate tablets | 107 |
| Total | 426 |
Baseline characteristics
| Characteristic | PPC-06 400 mg QD | PPC-06 400 mg BID | PPC-06 600 mg BID | Placebo BID | Total |
|---|---|---|---|---|---|
| Age, Continuous | 48.0 years STANDARD_DEVIATION 13.18 | 51.0 years STANDARD_DEVIATION 12.29 | 50.2 years STANDARD_DEVIATION 13.74 | 49.3 years STANDARD_DEVIATION 12.59 | 49.6 years STANDARD_DEVIATION 12.96 |
| Psoriasis Area and Severity Index (PASI) | 18.41 units on a scale STANDARD_DEVIATION 6.377 | 18.56 units on a scale STANDARD_DEVIATION 8.004 | 18.00 units on a scale STANDARD_DEVIATION 6.68 | 17.26 units on a scale STANDARD_DEVIATION 6.169 | 18.05 units on a scale STANDARD_DEVIATION 6.842 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 4 Participants | 11 Participants | 5 Participants | 26 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 2 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) White | 97 Participants | 96 Participants | 92 Participants | 97 Participants | 382 Participants |
| Region of Enrollment United States | 105 participants | 107 participants | 107 participants | 107 participants | 426 participants |
| Sex: Female, Male Female | 40 Participants | 43 Participants | 43 Participants | 43 Participants | 169 Participants |
| Sex: Female, Male Male | 65 Participants | 64 Participants | 64 Participants | 64 Participants | 257 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 105 | 0 / 107 | 0 / 106 | 0 / 107 |
| other Total, other adverse events | 30 / 105 | 42 / 107 | 68 / 106 | 9 / 107 |
| serious Total, serious adverse events | 3 / 105 | 3 / 107 | 0 / 106 | 2 / 107 |
Outcome results
Primary
Achieving Psoriasis Area and Severity Index (PASI) - 75 at the End of Week 24
The percentage of subjects who achieve a reduction of 75% or greater from Baseline in the Psoriasis Area and Severity Index (PASI-75) The PASI is a measure of the average redness, thickness, and scaliness of the lesions (each graded on a 0-4 scale) and is weighted by the area of involvement. The minimum possible score on this scale is '0', while the maximum score on this scale is 72. A lower score on this scale at the end of the study indicates an improvement in the condition of subject.
Time frame: End of Week 24
Population: Full Analysis Set (FAS) Population which included all randomized subjects who received at least one dose of IP and had at least one post-dose efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PPC-06 400 mg QD | Achieving Psoriasis Area and Severity Index (PASI) - 75 at the End of Week 24 | 39.7 percentage of total participants |
| PPC-06 400 mg BID | Achieving Psoriasis Area and Severity Index (PASI) - 75 at the End of Week 24 | 47.2 percentage of total participants |
| PPC-06 600 mg BID | Achieving Psoriasis Area and Severity Index (PASI) - 75 at the End of Week 24 | 44.3 percentage of total participants |
| Placebo BID | Achieving Psoriasis Area and Severity Index (PASI) - 75 at the End of Week 24 | 20.0 percentage of total participants |
Primary
Achieving the Investigator's Global Assessment (IGA) Score of 0 or 1
The Percentage of subjects who achieve the Investigator's Global Assessment (IGA) score of clear or almost clear (IGA score 0 or 1) Score Grade Definition 0 Clear: No signs of psoriasis 1. Almost clear: No thickening to minimal plaque elevation; Normal to slight pink coloration/faint erythema; Focal to minimal scaling 2. Mild: Slight elevation/thickening; Pink to light red coloration; Predominantly fine scaling partially or mostly covering lesions 3. Moderate: Clearly distinguishable/distinct thickening; Definite red coloration; Coarse scaling covering most plaques 4. Severe: Marked thickening with hard/sharp edges; Bright to deep dark red coloration; Thick/coarse scaling covering almost all or all lesions A lower score on this scale at the end of the study indicates an improvement in the disease condition.
Time frame: End of Week 24
Population: Full Analysis Set (FAS) Population included all randomized subjects who received at least one dose of IP and had at least one post-dose efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PPC-06 400 mg QD | Achieving the Investigator's Global Assessment (IGA) Score of 0 or 1 | 35.7 percentage of total participants |
| PPC-06 400 mg BID | Achieving the Investigator's Global Assessment (IGA) Score of 0 or 1 | 41.4 percentage of total participants |
| PPC-06 600 mg BID | Achieving the Investigator's Global Assessment (IGA) Score of 0 or 1 | 44.4 percentage of total participants |
| Placebo BID | Achieving the Investigator's Global Assessment (IGA) Score of 0 or 1 | 22.0 percentage of total participants |