Plaque Psoriasis
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of 3 doses of AGN-242428 in adult participants with moderate to severe plaque-type psoriasis.
Interventions
DRUGAGN-242428
AGN-242428 administered as an oral capsule(s) once daily.
DRUGPlacebo
Placebo administered as an oral capsule(s) once daily.
Sponsors
Vitae Pharmaceuticals, Inc.
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Participants who have a confirmed diagnosis of plaque psoriasis, diagnosed at least 6 months before study with a Physician's Global Assessment (PGA) score ≥ 3 at screening and baseline * Severity of disease must be at least moderate, defined as Psoriasis Area and Severity Index (PASI) ≥ 12 and % body surface area (BSA) ≥ 10 * Participant is a candidate for phototherapy or systemic therapy for psoriasis * Body weight of at least 55 kilograms (kg) (121 (pound) lbs)
Exclusion criteria
* Non-plaque forms of psoriasis (erythrodermic, guttate, pustular) or drug-induced psoriasis * Psoriasis which has not been stable for the 4 weeks prior to screening and which is unstable at Study Day 1 * History of Gilbert's, Rotor, or Dubin-Johnson syndromes or any other disorder of bilirubin metabolism * History of active mycobacterium tuberculosis (TB) infection or untreated or inadequately treated latent TB * Positive QuantiFERON test for TB infection at screening * Had a vaccination with Bacillus Calmette-Guérin (BCG) within 12 months prior to baseline * Positive drug and/or alcohol test at screening (with the exception of marijuana). Retesting in the case of a positive alcohol test is allowed at the discretion of the sponsor * Current treatment or history of treatment with any anti-Tumor Necrosis Factor alpha (TNFα) biologic therapy within 3 months or 5 half-lives of study, and/or all other biologics within 6 months of study (Day 1) * Efficacy failure on 2 or more biologic agents for the treatment of psoriasis when the failures occurred within 1 year of the initiation of the therapy of the first biologic agent * Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin (TBL) exceeding 1.5 times the upper limit of normal (ULN) at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving a Reduction (Improvement) in Psoriasis Area and Severity Index (PASI) Score of ≥ 75% From Baseline to Week 16 | Baseline (Day 1) to Week 16 | The PASI score ranges from 0-72 (with a higher score indicating greater severity of psoriasis), based on a combination of the severity (erythema, induration, and desquamation) of psoriasis and percentage of affected area. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving a Clear (0) or Almost Clear (1) Score in PGA at Week 16 | Week 16 | The investigator evaluated the participant's overall severity of psoriasis using the PGA 5-point scale (0 to 4) where 0=Clear to 4=Severe. |
| Percentage of Participants Achieving Reduction (Improvement) in PASI Score of ≥ 50% From Baseline to Week 16 | Baseline (Day 1) to Week 16 | The PASI score ranges from 0-72 (with a higher score indicating greater severity of psoriasis), based on a combination of the severity (erythema, induration, and desquamation) of psoriasis and percentage of affected area. |
| Percentage of Participants Achieving Reduction (Improvement) in PASI Score of ≥ 90% From Baseline to Week 16 | Baseline (Day 1) to Week 16 | The PASI score ranges from 0-72 (with a higher score indicating greater severity of psoriasis), based on a combination of the severity (erythema, induration, and desquamation) of psoriasis and percentage of affected area. |
| Percentage of Participants Achieving ≥ 2-point Reduction (Improvement) in Physician's Global Assessment (PGA) Score at Week 16 | Baseline (Day 1) to Week 16 | The investigator evaluated the participant's overall severity of psoriasis using the PGA 5-point scale (0 to 4) where 0=Clear and 4=Severe. |
| Number of Participants With TEAEs Leading to Discontinuation | First dose of study drug to the last dose of study drug (up to Week 12) plus approximately 30 days past last dose | An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An AE was considered a TEAE if the AE began or worsened (increased in severity or became serious) on or after the date of the first dose of study drug. |
| Number of Participants With TEAEs Considered Related to the Study Treatment as Per Investigator | First dose of study drug to the last dose of study drug (up to Week 12) plus approximately 30 days past last dose | An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An AE was considered a TEAE if the AE began or worsened (increased in severity or became serious) on or after the date of the first dose of study drug. The TEAEs related to the study drug, as assessed by Investigator are reported. |
| Plasma Concentration of AGN-242428 | Single sample predose at Week 4 and 8 Visits, single sample 1-2 hours postdose at Weeks 6 and 10 Visits | — |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | First dose of study drug to the last dose of study drug (up to Week 12) plus approximately 30 days past last dose | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An AE was considered a TEAE if the AE began or worsened (increased in severity or became serious) on or after the date of the first dose of study drug. |
Countries
United States
Participant flow
Pre-assignment details
As the study was terminated, no participants completed the planned dosing schedule of 16 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo-matching AGN-242428 capsules, oral administration, once-daily for up to 12 weeks. | 7 |
| AGN-242428 Higher Dose AGN-242428 capsules, oral administration, once-daily for up to 12 weeks. | 6 |
| AGN-242428 Medium Dose AGN-242428 capsules, oral administration, once-daily for up to 12 weeks. | 5 |
| AGN-242428 Lower Dose AGN-242428 capsule and placebo-matching AGN-242428 capsule, oral administration, once-daily for up to 12 weeks. | 4 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 2 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Overall Study | Study Terminated by Sponsor | 6 | 3 | 4 | 3 |
Baseline characteristics
| Characteristic | Placebo | AGN-242428 Higher Dose | AGN-242428 Medium Dose | AGN-242428 Lower Dose | Total |
|---|---|---|---|---|---|
| Age, Continuous | 46.3 years STANDARD_DEVIATION 16.87 | 50.8 years STANDARD_DEVIATION 10.83 | 52.0 years STANDARD_DEVIATION 10.02 | 44.8 years STANDARD_DEVIATION 11 | 48.5 years STANDARD_DEVIATION 12.43 |
| Psoriasis Area and Severity Index (PASI) Score at Baseline | 18.20 score on a scale STANDARD_DEVIATION 4.819 | 14.37 score on a scale STANDARD_DEVIATION 3.635 | 18.78 score on a scale STANDARD_DEVIATION 7.281 | 15.98 score on a scale STANDARD_DEVIATION 3.699 | 16.88 score on a scale STANDARD_DEVIATION 5.023 |
| Race/Ethnicity, Customized Asian | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 5 Participants | 3 Participants | 4 Participants | 3 Participants | 15 Participants |
| Race/Ethnicity, Customized White | 5 Participants | 6 Participants | 4 Participants | 4 Participants | 19 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 4 Participants | 4 Participants | 17 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 / 7 | 0 / 6 | 0 / 6 | 0 / 4 |
| other Total, other adverse events | 5 / 7 | 3 / 6 | 4 / 6 | 1 / 4 |
| serious Total, serious adverse events | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 4 |
Outcome results
Primary
Percentage of Participants Achieving a Reduction (Improvement) in Psoriasis Area and Severity Index (PASI) Score of ≥ 75% From Baseline to Week 16
The PASI score ranges from 0-72 (with a higher score indicating greater severity of psoriasis), based on a combination of the severity (erythema, induration, and desquamation) of psoriasis and percentage of affected area.
Time frame: Baseline (Day 1) to Week 16
Population: No data was collected for this Outcome Measure because the study was terminated and no participants reached the Week 16 timepoint.
Secondary
Number of Participants With TEAEs Considered Related to the Study Treatment as Per Investigator
An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An AE was considered a TEAE if the AE began or worsened (increased in severity or became serious) on or after the date of the first dose of study drug. The TEAEs related to the study drug, as assessed by Investigator are reported.
Time frame: First dose of study drug to the last dose of study drug (up to Week 12) plus approximately 30 days past last dose
Population: Safety population included all participants who received at least 1 administration of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With TEAEs Considered Related to the Study Treatment as Per Investigator | 1 Participants |
| AGN-242428 Higher Dose | Number of Participants With TEAEs Considered Related to the Study Treatment as Per Investigator | 3 Participants |
| AGN-242428 Medium Dose | Number of Participants With TEAEs Considered Related to the Study Treatment as Per Investigator | 3 Participants |
| AGN-242428 Lower Dose | Number of Participants With TEAEs Considered Related to the Study Treatment as Per Investigator | 1 Participants |
Secondary
Number of Participants With TEAEs Leading to Discontinuation
An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An AE was considered a TEAE if the AE began or worsened (increased in severity or became serious) on or after the date of the first dose of study drug.
Time frame: First dose of study drug to the last dose of study drug (up to Week 12) plus approximately 30 days past last dose
Population: Safety population included all participants who received at least 1 administration of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With TEAEs Leading to Discontinuation | 1 Participants |
| AGN-242428 Higher Dose | Number of Participants With TEAEs Leading to Discontinuation | 2 Participants |
| AGN-242428 Medium Dose | Number of Participants With TEAEs Leading to Discontinuation | 2 Participants |
| AGN-242428 Lower Dose | Number of Participants With TEAEs Leading to Discontinuation | 1 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An AE was considered a TEAE if the AE began or worsened (increased in severity or became serious) on or after the date of the first dose of study drug.
Time frame: First dose of study drug to the last dose of study drug (up to Week 12) plus approximately 30 days past last dose
Population: Safety population included all participants who received at least 1 administration of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 5 Participants |
| AGN-242428 Higher Dose | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 3 Participants |
| AGN-242428 Medium Dose | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 4 Participants |
| AGN-242428 Lower Dose | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 1 Participants |
Secondary
Percentage of Participants Achieving ≥ 2-point Reduction (Improvement) in Physician's Global Assessment (PGA) Score at Week 16
The investigator evaluated the participant's overall severity of psoriasis using the PGA 5-point scale (0 to 4) where 0=Clear and 4=Severe.
Time frame: Baseline (Day 1) to Week 16
Population: No data was collected for this Outcome Measure because the study was terminated and no participants reached the Week 16 timepoint.
Secondary
Percentage of Participants Achieving a Clear (0) or Almost Clear (1) Score in PGA at Week 16
The investigator evaluated the participant's overall severity of psoriasis using the PGA 5-point scale (0 to 4) where 0=Clear to 4=Severe.
Time frame: Week 16
Population: No data was collected for this Outcome Measure because the study was terminated and no participants reached the Week 16 timepoint.
Secondary
Percentage of Participants Achieving Reduction (Improvement) in PASI Score of ≥ 50% From Baseline to Week 16
The PASI score ranges from 0-72 (with a higher score indicating greater severity of psoriasis), based on a combination of the severity (erythema, induration, and desquamation) of psoriasis and percentage of affected area.
Time frame: Baseline (Day 1) to Week 16
Population: No data was collected for this Outcome Measure because the study was terminated and no participants reached the Week 16 timepoint.
Secondary
Percentage of Participants Achieving Reduction (Improvement) in PASI Score of ≥ 90% From Baseline to Week 16
The PASI score ranges from 0-72 (with a higher score indicating greater severity of psoriasis), based on a combination of the severity (erythema, induration, and desquamation) of psoriasis and percentage of affected area.
Time frame: Baseline (Day 1) to Week 16
Population: No data was collected for this Outcome Measure because the study was terminated and no participants reached the Week 16 primary timepoint.
Secondary
Plasma Concentration of AGN-242428
Time frame: Single sample predose at Week 4 and 8 Visits, single sample 1-2 hours postdose at Weeks 6 and 10 Visits
Population: Pharmacokinetic (PK) population included all participants who received AGN-242428 and had available plasma concentration data at the given timepoint. No PK data was collected at Week 12 for participants who received AGN-242428 or Week 16 as the study was terminated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentration of AGN-242428 | Week 4 | 1500 ng/mL | Standard Deviation 692 |
| Placebo | Plasma Concentration of AGN-242428 | Week 6 | 3720 ng/mL | — |
| Placebo | Plasma Concentration of AGN-242428 | Week 8 | 1300 ng/mL | — |
| AGN-242428 Higher Dose | Plasma Concentration of AGN-242428 | Week 10 | 483 ng/mL | — |
| AGN-242428 Higher Dose | Plasma Concentration of AGN-242428 | Week 6 | 1150 ng/mL | Standard Deviation 881 |
| AGN-242428 Higher Dose | Plasma Concentration of AGN-242428 | Week 4 | 1060 ng/mL | Standard Deviation 449 |
| AGN-242428 Higher Dose | Plasma Concentration of AGN-242428 | Week 8 | 886 ng/mL | Standard Deviation 376 |
| AGN-242428 Medium Dose | Plasma Concentration of AGN-242428 | Week 6 | 718 ng/mL | — |
| AGN-242428 Medium Dose | Plasma Concentration of AGN-242428 | Week 8 | 616 ng/mL | — |
| AGN-242428 Medium Dose | Plasma Concentration of AGN-242428 | Week 4 | 488 ng/mL | Standard Deviation 125 |