Plaque Psoriasis, Psoriasis Vulgaris
Conditions
Brief summary
The aim of this study is to evaluate safety, tolerability, and efficacy of PRCL-02 in moderate to severe chronic plaque psoriasis
Interventions
DRUGPRCL-02
Oral tablets
DRUGPlacebo
Oral tablets
Sponsors
PRCL Research Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Presents with moderate to severe psoriasis vulgaris based on: * Chronic psoriasis vulgaris for at least 6 months * Plaque psoriasis involving at least 10% body surface area (BSA) * Psoriasis Area and Severity Index (PASI) total score of at least 12 * Have at least 2 evaluable plaques located in 2 different body regions. (Also for participants who elect to have plaques biopsied, should be suitable for a total of 4 punch biopsies each, and one lesion, preferably on a region of the body that is not normally exposed (e.g., trunk), should be selected for biopsy) * Have a Static Physician's Global Assessment (sPGA) score of greater than or equal to (≥)3 * Are candidates for systemic therapy * Have a body mass index (BMI) within the range of 18 to 40 kilograms per square meter (kg/m2) * Women who are of childbearing potential must agree to use 1 highly effective method of contraception, or a combination of 2 effective methods of contraception for the entirety of the study * Women of non childbearing potential are defined as women who are: * Infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation), congenital anomaly such as mullerian agenesis; or * Post-menopausal, defined as either: * A woman at least 50 years of age with an intact uterus, not on hormone therapy, who has had either: cessation of menses for at least 1 year; or at least 6 months of spontaneous amenorrhea with a follicle stimulating hormone greater than (\>)40 milli-international units per milliliter (mIU/mL); or * A woman 55 years or older not on hormone therapy, who has had at least 6 months of spontaneous amenorrhea; or * A woman at least 55 years of age with a diagnosis of menopause prior to staring hormone replacement therapy
Exclusion criteria
* Currently enrolled in any other clinical trial involving a study drug or device, or any other type of medical research judged not compatible with this study (Participants in the previous PRCL study (SMAD) will be allowed to be included in this study, provided that they meet all inclusion and none of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Psoriasis Area and Severity Index ≥75% (PASI 75) Improvement | Baseline to week 12 | Following 12 weeks of treatment. The Psoriasis Area and Severity Index (PASI) scores the severity of disease on a scale from 0 to 72 (where a score of 72 indicates extreme disease severity). PASI 75 indicates 75% improvement from baseline to Week 12 in the Psoriasis Area and Severity Index |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Treatment Emergent Adverse Event | Baseline up to week 18 | Following 12 weeks of treatment |
| Area Under the Concentration Time Curve (AUC0-τ) | Predose and 1, 2, 4, 8, 336, 672, 1008, 1344 hours post dose, on Day 84 | Steady state after 12 weeks of treatment |
| Maximum Observed Drug Concentration (Cmax) | Predose and 1, 2, 4, 8, 336, 672, 1008, 1344 hours post dose, on Day 84 | Steady state after 12 weeks of treatment |
| Time to Reach Maximum Observed Drug Concentration (Tmax) | Predose and 1, 2, 4, 8, 336, 672, 1008, 1344 hours post dose, on Day 84 | Steady state after 12 weeks of treatment |
Countries
Canada, Slovakia, Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PRCL-02 25 Milligrams (mg) Loading dose of 150 mg followed by a once daily maintenance dose commencing on Day 2 and continuing for 12 weeks
PRCL-02: Oral tablets | 31 |
| PRCL-02 50 mg Loading dose of 300 mg followed by a once daily maintenance dose commencing on Day 2 and continuing for 12 weeks
PRCL-02: Oral tablets | 30 |
| Placebo Loading dose followed by a once daily maintenance dose at matching treatment levels, commencing on Day 2 and continuing for 12 weeks
Placebo: Oral tablets | 31 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 0 |
| Overall Study | Dizziness and Rash | 0 | 1 | 0 |
| Overall Study | Exacerbation of Psoriasis | 0 | 1 | 0 |
| Overall Study | High Neutrophils | 0 | 0 | 2 |
| Overall Study | Participant Did Not Return for Visit | 0 | 1 | 0 |
| Overall Study | Patient Did Not Meet Eligibility | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 3 |
Baseline characteristics
| Characteristic | PRCL-02 25 Milligrams (mg) | Total | Placebo | PRCL-02 50 mg |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 4 Participants | 2 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 88 Participants | 29 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 92 Participants | 31 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 27 Participants | 87 Participants | 31 Participants | 29 Participants |
| Region of Enrollment Canada | 9 participants | 22 participants | 6 participants | 7 participants |
| Region of Enrollment Slovakia | 13 participants | 36 participants | 10 participants | 13 participants |
| Region of Enrollment Ukraine | 9 participants | 34 participants | 15 participants | 10 participants |
| Sex: Female, Male Female | 14 Participants | 33 Participants | 8 Participants | 11 Participants |
| Sex: Female, Male Male | 17 Participants | 59 Participants | 23 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 30 | 0 / 31 |
| other Total, other adverse events | 3 / 31 | 3 / 30 | 4 / 31 |
| serious Total, serious adverse events | 1 / 31 | 0 / 30 | 0 / 31 |
Outcome results
Primary
Percentage of Participants Achieving Psoriasis Area and Severity Index ≥75% (PASI 75) Improvement
Following 12 weeks of treatment. The Psoriasis Area and Severity Index (PASI) scores the severity of disease on a scale from 0 to 72 (where a score of 72 indicates extreme disease severity). PASI 75 indicates 75% improvement from baseline to Week 12 in the Psoriasis Area and Severity Index
Time frame: Baseline to week 12
Population: Intent to treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRCL-02 25 Milligrams (mg) | Percentage of Participants Achieving Psoriasis Area and Severity Index ≥75% (PASI 75) Improvement | 4 Participants |
| PRCL-02 50 mg | Percentage of Participants Achieving Psoriasis Area and Severity Index ≥75% (PASI 75) Improvement | 1 Participants |
| Placebo | Percentage of Participants Achieving Psoriasis Area and Severity Index ≥75% (PASI 75) Improvement | 0 Participants |
Secondary
Area Under the Concentration Time Curve (AUC0-τ)
Steady state after 12 weeks of treatment
Time frame: Predose and 1, 2, 4, 8, 336, 672, 1008, 1344 hours post dose, on Day 84
Population: Pharmacokinetic (PK) evaluable
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PRCL-02 25 Milligrams (mg) | Area Under the Concentration Time Curve (AUC0-τ) | 165000 h*mg/mL | Geometric Coefficient of Variation 627 |
| PRCL-02 50 mg | Area Under the Concentration Time Curve (AUC0-τ) | 439000 h*mg/mL | Geometric Coefficient of Variation 492 |
Secondary
Maximum Observed Drug Concentration (Cmax)
Steady state after 12 weeks of treatment
Time frame: Predose and 1, 2, 4, 8, 336, 672, 1008, 1344 hours post dose, on Day 84
Population: Pharmacokinetic (PK) evaluable
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PRCL-02 25 Milligrams (mg) | Maximum Observed Drug Concentration (Cmax) | 984 ng/mL | Geometric Coefficient of Variation 200 |
| PRCL-02 50 mg | Maximum Observed Drug Concentration (Cmax) | 2220 ng/mL | Geometric Coefficient of Variation 139 |
Secondary
Number of Participants With Any Treatment Emergent Adverse Event
Following 12 weeks of treatment
Time frame: Baseline up to week 18
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRCL-02 25 Milligrams (mg) | Number of Participants With Any Treatment Emergent Adverse Event | 14 Participants |
| PRCL-02 50 mg | Number of Participants With Any Treatment Emergent Adverse Event | 12 Participants |
| Placebo | Number of Participants With Any Treatment Emergent Adverse Event | 10 Participants |
Secondary
Time to Reach Maximum Observed Drug Concentration (Tmax)
Steady state after 12 weeks of treatment
Time frame: Predose and 1, 2, 4, 8, 336, 672, 1008, 1344 hours post dose, on Day 84
Population: Pharmacokinetic (PK) evaluable
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PRCL-02 25 Milligrams (mg) | Time to Reach Maximum Observed Drug Concentration (Tmax) | 2.0 hours |
| PRCL-02 50 mg | Time to Reach Maximum Observed Drug Concentration (Tmax) | 4.00 hours |