Psoriasis
Conditions
Keywords
Psoriasis, Risankizumab, Plaque, Skyrizi
Brief summary
This pilot study explores higher than standard doses of risankizumab for plaque psoriasis, to see effects on resident memory T cells and skin clearance.
Detailed description
This is a pilot study that explores whether higher initial doses of risankizumab (300 mg and 600 mg, 2 times and 4 times the standard initial doses for plaque psoriasis) can more effectively target resident memory T cells, a type of immune cell within psoriatic lesions, and whether this results in higher levels of completely clear skin and for longer periods of time following withdrawal of drug. It is believed that resident memory T cells in psoriatic skin contribute to the persistence of psoriasis. It is believed that if the study drug can more effectively eliminate these cells, better clearance of psoriasis may be achieved (when compared to standard initial doses of study drug).
Interventions
DRUGrisankizumab
Risankizumab (Skyrizi) is an anti-IL-23 antibody being investigated for the treatment of multiple inflammatory diseases, including psoriasis, Crohn's disease, ulcerative colitis, and psoriatic arthritis.
Sponsors
AbbVie
Oregon Medical Research Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has provided written consent * Subject has the ability to comply with all study visits and procedures * Subject is at least 18 years of age * Subject has chronic stable plaque psoriasis for at least 6 months and with a severity of BSA greater than or equal to 10 and PASI greater than or equal to 12 * Female subjects of child-bearing potential must have a negative urine test at screening and baseline. Female subjects must be either postmenopausal, or permanently surgically sterile, or for women of child-bearing potential practicing at least one form of birth control
Exclusion criteria
* Breastfeeding or pregnant women, or women who plan to become pregnant during study period * Participation in any other clinical trial * Active infection with HIV, hepatitis B virus, or hepatitis C virus * Active infection with tuberculosis or untreated latent tuberculosis * History of known active cancer, other than non-melanoma skin cancer or cervical carcinoma in situ, in the past 3 years * History of drug or alcohol abuse in the past 6 months, as per investigator's assessment * History of suicidal ideation or attempts in the past 6 months * Presence of any concurrent illness, which in the opinion of the investigator, would place the patient at unnecessary safety risk during the trial or interfere with completion of the trial * Treatment with topical medications for psoriasis in the past 2 weeks * Treatment with oral medications for psoriasis in the past 4 weeks * Phototherapy for psoriasis in the past 4 weeks * Any prior treatment with Risankizumab * Treatment with biologic medications for psoriasis (other than Risankizumab) in the past 4 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CD8+ Trm1 Cells in Lesional Skin at Baseline and Week 52 | 52 weeks | The number of lesional CD8+ Trm1 cells at baseline and Week 52 was calculated by longitudinal single-cell RNA-sequencing of full-thickness skin biopsy samples. Uniform Manifold Approximation Projection (UMAP) was used for T cell subtype visualization and CD8+ Trm1 cells were identified as IFNγ+/CD8+/CD69+ T cells. |
| CD8+ Trm17 Cells in Lesional Skin at Baseline and Week 52 | 52 weeks | The number of lesional CD8+ Trm17 cells at baseline and Week 52 was calculated by longitudinal single-cell RNA-sequencing of full-thickness skin biopsy samples. Uniform Manifold Approximation Projection (UMAP) was used for T cell subtype visualization and CD8+ Trm17 cells were identified as IFNγ+/CD8+/CD69+ T cells. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PASI 100 Results in Patients Receiving 4X Standard Induction Doses of Risankizumab vs. Those Receiving 2X Standard Induction Doses of Risankizumab. | Enrollment to Week 52 | The percentage of patients with Psoriasis Area and Severity Index (PASI) 100 (complete clearance) at Weeks 28, 40, and 52 in patients receiving 4X standard induction doses of risankizumab vs. those receiving 2X standard induction doses of risankizumab. |
| Safety Events | Enrollment to Week 52 | Safety events over 52 weeks in patients receiving 4X standard induction doses of risankizumab vs. those receiving 2X standard induction doses of risankizumab. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 600 mg Dose Group Received risankizumab subcutaneous injection 600 mg (4x dosing) at Weeks 0, 4, and 16 and then no further injections. Subjects were followed through week 100, the first 52 weeks in a double-blind manner, then the next 48 weeks in an unblinded extension period. | 10 |
| 300 mg Dose Group Received risankizumab subcutaneous injection 300 mg (2x dosing) at Weeks 0, 4, and 16 and then no further injections. Subjects were followed through week 100, the first 52 weeks in a double-blind manner, then the next 48 weeks in an unblinded extension period. | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Total | 600 mg Dose Group | 300 mg Dose Group |
|---|---|---|---|
| Age, Continuous | 46.8 years STANDARD_DEVIATION 14.5 | 44.9 years STANDARD_DEVIATION 16.3 | 48.7 years STANDARD_DEVIATION 13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 10 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Psoriasis disease duration | 21.4 years STANDARD_DEVIATION 16.9 | 26.0 years STANDARD_DEVIATION 18.1 | 16.9 years STANDARD_DEVIATION 15.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 8 Participants | 8 Participants |
| Sex: Female, Male Female | 7 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 13 Participants | 6 Participants | 7 Participants |
| sPGA sPGA 3 (moderate) | 13 Participants | 4 Participants | 9 Participants |
| sPGA sPGA 4 (severe) | 7 Participants | 6 Participants | 1 Participants |
| Weight | 87.6 kg STANDARD_DEVIATION 17.1 | 88.42 kg STANDARD_DEVIATION 20.7 | 86.7 kg STANDARD_DEVIATION 13.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 7 / 10 | 9 / 10 |
| serious Total, serious adverse events | 0 / 10 | 1 / 10 |
Outcome results
Primary
CD8+ Trm17 Cells in Lesional Skin at Baseline and Week 52
The number of lesional CD8+ Trm17 cells at baseline and Week 52 was calculated by longitudinal single-cell RNA-sequencing of full-thickness skin biopsy samples. Uniform Manifold Approximation Projection (UMAP) was used for T cell subtype visualization and CD8+ Trm17 cells were identified as IFNγ+/CD8+/CD69+ T cells.
Time frame: 52 weeks
Population: Cell counts from all participants were analyzed together at baseline given the exploratory nature of this study, the small number of overall participants and the selection of trial participants on the basis of clinical parameters that assume a similar degree of memory cell infiltrate in lesional psoriasis plaques.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 600 mg Baseline | CD8+ Trm17 Cells in Lesional Skin at Baseline and Week 52 | 19.67 number of cells |
| 300 mg Baseline | CD8+ Trm17 Cells in Lesional Skin at Baseline and Week 52 | 22.88 number of cells |
| 600 mg Week 52 | CD8+ Trm17 Cells in Lesional Skin at Baseline and Week 52 | 3.20 number of cells |
| 300 mg Week 52 | CD8+ Trm17 Cells in Lesional Skin at Baseline and Week 52 | 5.00 number of cells |
Primary
CD8+ Trm1 Cells in Lesional Skin at Baseline and Week 52
The number of lesional CD8+ Trm1 cells at baseline and Week 52 was calculated by longitudinal single-cell RNA-sequencing of full-thickness skin biopsy samples. Uniform Manifold Approximation Projection (UMAP) was used for T cell subtype visualization and CD8+ Trm1 cells were identified as IFNγ+/CD8+/CD69+ T cells.
Time frame: 52 weeks
Population: Cell counts from all participants were analyzed together at baseline given the exploratory nature of this study, the small number of overall participants and the selection of trial participants on the basis of clinical parameters that assume a similar degree of memory cell infiltrate in lesional psoriasis plaques.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 600 mg Baseline | CD8+ Trm1 Cells in Lesional Skin at Baseline and Week 52 | 9.60 number of cells |
| 300 mg Baseline | CD8+ Trm1 Cells in Lesional Skin at Baseline and Week 52 | 26.71 number of cells |
| 600 mg Week 52 | CD8+ Trm1 Cells in Lesional Skin at Baseline and Week 52 | 1.60 number of cells |
| 300 mg Week 52 | CD8+ Trm1 Cells in Lesional Skin at Baseline and Week 52 | 16.63 number of cells |
Secondary
PASI 100 Results in Patients Receiving 4X Standard Induction Doses of Risankizumab vs. Those Receiving 2X Standard Induction Doses of Risankizumab.
The percentage of patients with Psoriasis Area and Severity Index (PASI) 100 (complete clearance) at Weeks 28, 40, and 52 in patients receiving 4X standard induction doses of risankizumab vs. those receiving 2X standard induction doses of risankizumab.
Time frame: Enrollment to Week 52
Population: 18 total subjects completed all 3 risankizumab injections and were considered evaluable in efficacy assessments
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 600 mg Baseline | PASI 100 Results in Patients Receiving 4X Standard Induction Doses of Risankizumab vs. Those Receiving 2X Standard Induction Doses of Risankizumab. | PASI 100 at week 28 | 7 Participants |
| 600 mg Baseline | PASI 100 Results in Patients Receiving 4X Standard Induction Doses of Risankizumab vs. Those Receiving 2X Standard Induction Doses of Risankizumab. | PASI 100 at week 40 | 6 Participants |
| 600 mg Baseline | PASI 100 Results in Patients Receiving 4X Standard Induction Doses of Risankizumab vs. Those Receiving 2X Standard Induction Doses of Risankizumab. | PASI 100 at week 52 | 4 Participants |
| 300 mg Baseline | PASI 100 Results in Patients Receiving 4X Standard Induction Doses of Risankizumab vs. Those Receiving 2X Standard Induction Doses of Risankizumab. | PASI 100 at week 28 | 8 Participants |
| 300 mg Baseline | PASI 100 Results in Patients Receiving 4X Standard Induction Doses of Risankizumab vs. Those Receiving 2X Standard Induction Doses of Risankizumab. | PASI 100 at week 40 | 6 Participants |
| 300 mg Baseline | PASI 100 Results in Patients Receiving 4X Standard Induction Doses of Risankizumab vs. Those Receiving 2X Standard Induction Doses of Risankizumab. | PASI 100 at week 52 | 4 Participants |
Secondary
Safety Events
Safety events over 52 weeks in patients receiving 4X standard induction doses of risankizumab vs. those receiving 2X standard induction doses of risankizumab.
Time frame: Enrollment to Week 52
Population: Treatment emergent adverse events
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 600 mg Baseline | Safety Events | TEAE | 11 events |
| 600 mg Baseline | Safety Events | TEAE related to study treatment | 0 events |
| 600 mg Baseline | Safety Events | Serious or severe TEAE | 0 events |
| 600 mg Baseline | Safety Events | Serious TEAE related to study treatment | 0 events |
| 300 mg Baseline | Safety Events | Serious TEAE related to study treatment | 0 events |
| 300 mg Baseline | Safety Events | TEAE | 11 events |
| 300 mg Baseline | Safety Events | Serious or severe TEAE | 1 events |
| 300 mg Baseline | Safety Events | TEAE related to study treatment | 0 events |