Plaque Psoriasis
Conditions
Keywords
Mild to Moderate Chronic Plaque Psoriasis
Brief summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of 12 weeks of treatment with Apo805K1 in subjects with moderate to severe chronic plaque psoriasis.
Detailed description
A) To evaluate the safety and tolerability of 12 weeks of treatment with Apo805K1 B) To evaluate the pharmacokinetics of Apo805K1 following daily administration for 14 days C) To evaluate the efficacy and pharmacodynamics of Apo805K1
Interventions
DRUGApo805K1
Sequential parallel dose escalation.
Sponsors
ApoPharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * A clinical diagnosis of moderate to severe chronic plaque psoriasis for at least 6 months (before Baseline assessment) with current body surface area (BSA) involvement ≥10% and Psoriasis Area Severity Index (PASI) ≥10. * Male and female subjects 18 to 65 years of age, inclusive. * At least one psoriatic plaque ≥6 mm in diameter (in a location suitable for biopsy). * Signed and witnessed written informed consent form obtained prior to the first study intervention, as well as the ability to adhere to study restrictions, appointments and evaluation schedule. Main
Exclusion criteria
* Treatment of psoriasis with biologic agents within 90 days prior to Baseline assessment and during the study. * Treatment with methotrexate, cyclosporine, retinoids, hydroxyurea or other systemic agents within 30 days prior to Baseline assessment and during the study. * Phototherapy within 30 days prior to Baseline assessment and during the study. * Psoriasis topical therapy within 14 days prior to Baseline assessment and during the study (exception: non-medicated emollients and tar shampoo will be allowed). * History of liver disease or abnormal liver enzymes * Serum creatinine ≥1.5 times the upper limit of normal for age and sex-matched controls. * Previous treatment with Apo805K1or Thymodepressin or other immunosuppressant drugs. * Evidence of skin conditions other than psoriasis (e.g., eczema) that could interfere with psoriasis assessments. * History of chronic infection or malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Adverse Events | 12 Weeks | The number of patients in each treatment group who reported at least 1 adverse event, including clinically significant changes from baseline in vital signs, 12-lead ECG, physical examinations and laboratory tests, from the time of the first dose until the last study visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 12 hours | Tmax for dosages of 10 mg, 30 mg, 60 mg, or 100 mg Apo805K1, determined on Day 14. Serial blood samples for PK analysis were collected pre-dose and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose. |
| AUC 0-infinity of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 12 hours | AUC 0-infinity for dosages of 10 mg, 30 mg, 60 mg, or 100 mg Apo805K1, determined on Day 14. Serial blood samples for PK analysis were collected pre-dose and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose. |
| T 1/2 of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 12 hours | T 1/2 for dosages of 10 mg, 30 mg, 60 mg, or 100 mg Apo805K1, determined on Day 14. Serial blood samples for PK analysis were collected pre-dose and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose. |
| Cmax of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 12 hours | Cmax for dosages of 10 mg, 30 mg, 60 mg, or 100 mg Apo805K1, determined on Day 14. Serial blood samples for PK analysis were collected pre-dose and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose. . |
| Efficacy of APO805K1 as Assessed by Achievement of PASI-75 | 12 weeks | The proportion of patients in each treatment group who achieved at least a 75% improvement in PASI score from baseline at Week 12 |
| Efficacy of Apo805K1 as Assessed by Change From Baseline at Week 12 in Lattice System-Physician Global Assessment (LS-PGA) Scores | Baseline to 12 weeks | The LS-PGA is a standardized method for determining categories of psoriasis severity. The percentage of body surface area involved is assessed on a scale ranging from 1 (0%) to 7 (51-100%); measures of plaque severity (thickness, erythema, and scaling) are assessed using a 4-point scale ranging from none to marked; and an algorithm is used to combine the above scores to determine a final score on a scale ranging from 0 (clear) to 7 (very severe). Thus, a decrease in LS-PGA score indicates improvement. This outcome measure compared the difference in change in LS-PGA score from baseline to Week 12 between the active treatment groups and the placebo group. |
| Efficacy of Apo805K1 as Assessed by Change From Baseline to Week 12 in Physician Global Assessment (PGA) Score | Baseline to 12 weeks | In the PGA, the physician assigns a single estimate of a patient's overall severity of the disease using a scale ranging from 0 (Clear) to 7 (Severe). (Unlike the LS-PGA, the individual elements of psoriasis plaque morphology or degree of body surface area involvement are not quantified.) Thus, a decrease in PGA score indicates improvement. This outcome measure compared the difference in change in PGA score from baseline to Week 12 between the active treatment groups and the placebo group. |
| Efficacy of Apo805K1 as Assessed by Change From Baseline in Psoriasis Area Severity Index (PASI) Scores | Baseline to 12 Weeks | PASI is a quantitative measure of psoriasis that combines an assessment of the severity of lesions and a measurement of how much of the body surface area is affected into a single score ranging from 0 (no disease) to 72 (maximal disease). Thus, a decrease in PASI score indicates improvement. This outcome measure compared the difference in change in PASI score from baseline to Week 12 between the active treatment groups and the placebo group. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Three patients in each of the 4 dose-escalating cohorts were randomized to receive placebo tablets that matched the active product in size and number (one 10 mg tablet, three 10 mg tablets, one 50 mg plus one 10 mg tablet, or two 50 mg tablets, respectively), daily for 12 weeks. The data of all placebo recipients were pooled for analyses. | 12 |
| Apo805K1 10 mg Patients in this treatment group received a single 10 mg tablet of Apo805K1 daily for 12 weeks | 12 |
| Apo805K1 30 mg Patients in this treatment group received three 10 mg tablets of Apo805K1 daily for 12 weeks | 12 |
| Apo805K1 60 mg Patients in this treatment group received one 10 mg tablet plus one 50 mg tablet of Apo805K1 daily for 12 weeks | 12 |
| Apo805K1 100 mg Patients in this treatment group received two 50 mg tablets of Apo805K1 daily for 12 weeks | 12 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Non-compliance | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Sponsor concern over ECG result | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Apo805K1 10 mg | Apo805K1 30 mg | Apo805K1 60 mg | Apo805K1 100 mg | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 12 Participants | 12 Participants | 12 Participants | 12 Participants | 60 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 0 Participants | 1 Participants | 3 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 8 Participants | 10 Participants | 10 Participants | 9 Participants | 46 Participants |
| Region of Enrollment Canada | 1 participants | 0 participants | 0 participants | 3 participants | 5 participants | 9 participants |
| Region of Enrollment United States | 11 participants | 12 participants | 12 participants | 9 participants | 7 participants | 51 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 8 Participants | 3 Participants | 0 Participants | 19 Participants |
| Sex: Female, Male Male | 9 Participants | 7 Participants | 4 Participants | 9 Participants | 12 Participants | 41 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 12 | 5 / 12 | 7 / 12 | 6 / 12 | 5 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 1 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Number of Patients With Adverse Events
The number of patients in each treatment group who reported at least 1 adverse event, including clinically significant changes from baseline in vital signs, 12-lead ECG, physical examinations and laboratory tests, from the time of the first dose until the last study visit.
Time frame: 12 Weeks
Population: The Safety Population consisted of all patients who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Patients With Adverse Events | 4 participants |
| Apo805K1 10 mg | Number of Patients With Adverse Events | 5 participants |
| Apo805K1 30 mg | Number of Patients With Adverse Events | 7 participants |
| Apo805K1 60 mg | Number of Patients With Adverse Events | 6 participants |
| Apo805K1 100 mg | Number of Patients With Adverse Events | 5 participants |
Secondary
AUC 0-infinity of Apo805K1 Following Multiple Doses, Assessed at Day 14
AUC 0-infinity for dosages of 10 mg, 30 mg, 60 mg, or 100 mg Apo805K1, determined on Day 14. Serial blood samples for PK analysis were collected pre-dose and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose.
Time frame: 12 hours
Population: The Pharmacokinetics Population consisted of all patients who received Apo805K1 and provided evaluable PK data on at least one visit (Day 1 or Day 14)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC 0-infinity of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 134.7 ng *hr/mL | Standard Deviation 68.1 |
| Apo805K1 10 mg | AUC 0-infinity of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 368.4 ng *hr/mL | Standard Deviation 244.6 |
| Apo805K1 30 mg | AUC 0-infinity of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 973.7 ng *hr/mL | Standard Deviation 463.1 |
| Apo805K1 60 mg | AUC 0-infinity of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 1294.0 ng *hr/mL | Standard Deviation 658.7 |
Secondary
Cmax of Apo805K1 Following Multiple Doses, Assessed at Day 14
Cmax for dosages of 10 mg, 30 mg, 60 mg, or 100 mg Apo805K1, determined on Day 14. Serial blood samples for PK analysis were collected pre-dose and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose. .
Time frame: 12 hours
Population: The Pharmacokinetics Population consisted of all patients who received Apo805K1 and provided evaluable PK data on at least one visit (Day 1 or Day 14)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cmax of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 18.3 ng/mL | Standard Deviation 9.7 |
| Apo805K1 10 mg | Cmax of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 53.0 ng/mL | Standard Deviation 37.8 |
| Apo805K1 30 mg | Cmax of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 138.5 ng/mL | Standard Deviation 54.5 |
| Apo805K1 60 mg | Cmax of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 164.9 ng/mL | Standard Deviation 69.2 |
Secondary
Efficacy of APO805K1 as Assessed by Achievement of PASI-75
The proportion of patients in each treatment group who achieved at least a 75% improvement in PASI score from baseline at Week 12
Time frame: 12 weeks
Population: The Efficacy Population was defined as all patients who received at least 1 dose of study medication and completed at least 1 post-baseline efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Efficacy of APO805K1 as Assessed by Achievement of PASI-75 | 16.7 percentage of patients |
| Apo805K1 10 mg | Efficacy of APO805K1 as Assessed by Achievement of PASI-75 | 16.7 percentage of patients |
| Apo805K1 30 mg | Efficacy of APO805K1 as Assessed by Achievement of PASI-75 | 0.0 percentage of patients |
| Apo805K1 60 mg | Efficacy of APO805K1 as Assessed by Achievement of PASI-75 | 0.0 percentage of patients |
| Apo805K1 100 mg | Efficacy of APO805K1 as Assessed by Achievement of PASI-75 | 8.3 percentage of patients |
p-value: 0.1975Cochran-Armitage trend test
Secondary
Efficacy of Apo805K1 as Assessed by Change From Baseline at Week 12 in Lattice System-Physician Global Assessment (LS-PGA) Scores
The LS-PGA is a standardized method for determining categories of psoriasis severity. The percentage of body surface area involved is assessed on a scale ranging from 1 (0%) to 7 (51-100%); measures of plaque severity (thickness, erythema, and scaling) are assessed using a 4-point scale ranging from none to marked; and an algorithm is used to combine the above scores to determine a final score on a scale ranging from 0 (clear) to 7 (very severe). Thus, a decrease in LS-PGA score indicates improvement. This outcome measure compared the difference in change in LS-PGA score from baseline to Week 12 between the active treatment groups and the placebo group.
Time frame: Baseline to 12 weeks
Population: The Efficacy Population was defined as all patients who received at least 1 dose of study medication and completed at least 1 post-baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Efficacy of Apo805K1 as Assessed by Change From Baseline at Week 12 in Lattice System-Physician Global Assessment (LS-PGA) Scores | -0.8 units on a scale | Standard Deviation 0.8 |
| Apo805K1 10 mg | Efficacy of Apo805K1 as Assessed by Change From Baseline at Week 12 in Lattice System-Physician Global Assessment (LS-PGA) Scores | -1.2 units on a scale | Standard Deviation 1.6 |
| Apo805K1 30 mg | Efficacy of Apo805K1 as Assessed by Change From Baseline at Week 12 in Lattice System-Physician Global Assessment (LS-PGA) Scores | -0.6 units on a scale | Standard Deviation 0.7 |
| Apo805K1 60 mg | Efficacy of Apo805K1 as Assessed by Change From Baseline at Week 12 in Lattice System-Physician Global Assessment (LS-PGA) Scores | -0.5 units on a scale | Standard Deviation 0.9 |
| Apo805K1 100 mg | Efficacy of Apo805K1 as Assessed by Change From Baseline at Week 12 in Lattice System-Physician Global Assessment (LS-PGA) Scores | -0.7 units on a scale | Standard Deviation 1.2 |
p-value: 0.6349Kruskal-Wallis
Secondary
Efficacy of Apo805K1 as Assessed by Change From Baseline in Psoriasis Area Severity Index (PASI) Scores
PASI is a quantitative measure of psoriasis that combines an assessment of the severity of lesions and a measurement of how much of the body surface area is affected into a single score ranging from 0 (no disease) to 72 (maximal disease). Thus, a decrease in PASI score indicates improvement. This outcome measure compared the difference in change in PASI score from baseline to Week 12 between the active treatment groups and the placebo group.
Time frame: Baseline to 12 Weeks
Population: The Efficacy Population was defined as all patients who received at least 1 dose of study medication and completed at least 1 post-baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Efficacy of Apo805K1 as Assessed by Change From Baseline in Psoriasis Area Severity Index (PASI) Scores | -3.8 units on a scale | Standard Deviation 4.6 |
| Apo805K1 10 mg | Efficacy of Apo805K1 as Assessed by Change From Baseline in Psoriasis Area Severity Index (PASI) Scores | -3.8 units on a scale | Standard Deviation 6.9 |
| Apo805K1 30 mg | Efficacy of Apo805K1 as Assessed by Change From Baseline in Psoriasis Area Severity Index (PASI) Scores | -2.0 units on a scale | Standard Deviation 5.3 |
| Apo805K1 60 mg | Efficacy of Apo805K1 as Assessed by Change From Baseline in Psoriasis Area Severity Index (PASI) Scores | -3.4 units on a scale | Standard Deviation 3.5 |
| Apo805K1 100 mg | Efficacy of Apo805K1 as Assessed by Change From Baseline in Psoriasis Area Severity Index (PASI) Scores | -2.8 units on a scale | Standard Deviation 5 |
Comparison: The difference in change in PASI score from baseline to Week 12 was compared all active treatment groups and the placebo groupp-value: 0.9048ANOVA
Secondary
Efficacy of Apo805K1 as Assessed by Change From Baseline to Week 12 in Physician Global Assessment (PGA) Score
In the PGA, the physician assigns a single estimate of a patient's overall severity of the disease using a scale ranging from 0 (Clear) to 7 (Severe). (Unlike the LS-PGA, the individual elements of psoriasis plaque morphology or degree of body surface area involvement are not quantified.) Thus, a decrease in PGA score indicates improvement. This outcome measure compared the difference in change in PGA score from baseline to Week 12 between the active treatment groups and the placebo group.
Time frame: Baseline to 12 weeks
Population: The Efficacy Population was defined as all patients who received at least 1 dose of study medication and completed at least 1 post-baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Efficacy of Apo805K1 as Assessed by Change From Baseline to Week 12 in Physician Global Assessment (PGA) Score | -1.0 units on a scale | Standard Deviation 1 |
| Apo805K1 10 mg | Efficacy of Apo805K1 as Assessed by Change From Baseline to Week 12 in Physician Global Assessment (PGA) Score | -0.8 units on a scale | Standard Deviation 1 |
| Apo805K1 30 mg | Efficacy of Apo805K1 as Assessed by Change From Baseline to Week 12 in Physician Global Assessment (PGA) Score | -0.5 units on a scale | Standard Deviation 1.1 |
| Apo805K1 60 mg | Efficacy of Apo805K1 as Assessed by Change From Baseline to Week 12 in Physician Global Assessment (PGA) Score | -0.9 units on a scale | Standard Deviation 0.8 |
| Apo805K1 100 mg | Efficacy of Apo805K1 as Assessed by Change From Baseline to Week 12 in Physician Global Assessment (PGA) Score | -1.3 units on a scale | Standard Deviation 1.1 |
p-value: 0.6212Kruskal-Wallis
Secondary
T 1/2 of Apo805K1 Following Multiple Doses, Assessed at Day 14
T 1/2 for dosages of 10 mg, 30 mg, 60 mg, or 100 mg Apo805K1, determined on Day 14. Serial blood samples for PK analysis were collected pre-dose and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose.
Time frame: 12 hours
Population: The Pharmacokinetics Population consisted of all patients who received Apo805K1 and provided evaluable PK data on at least one visit (Day 1 or Day 14)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | T 1/2 of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 2.8 hour | Standard Deviation 0.5 |
| Apo805K1 10 mg | T 1/2 of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 2.6 hour | Standard Deviation 0.2 |
| Apo805K1 30 mg | T 1/2 of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 2.8 hour | Standard Deviation 1.1 |
| Apo805K1 60 mg | T 1/2 of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 2.8 hour | Standard Deviation 0.5 |
Secondary
Tmax of Apo805K1 Following Multiple Doses, Assessed at Day 14
Tmax for dosages of 10 mg, 30 mg, 60 mg, or 100 mg Apo805K1, determined on Day 14. Serial blood samples for PK analysis were collected pre-dose and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose.
Time frame: 12 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Tmax of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 4.00 hour |
| Apo805K1 10 mg | Tmax of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 3.00 hour |
| Apo805K1 30 mg | Tmax of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 3.00 hour |
| Apo805K1 60 mg | Tmax of Apo805K1 Following Multiple Doses, Assessed at Day 14 | 4.00 hour |