Psoriasis
Conditions
Brief summary
This Phase 1 study will evaluate safety, tolerability, PK and PD of AMG 827 when administered as a single SC or IV dose.
Detailed description
This Phase 1 study will evaluate safety, tolerability, PK and PD of AMG 827 when administered as a single SC or IV dose in healthy subjects (Part A) and subjects with moderate to severe psoriasis (Part B).
Interventions
DRUG700 mg IV
single SC or IV dose in healthy subjects (Part A) and subjects with moderate to severe psoriasis (Part B).
DRUG350 mg SC
single SC or IV dose in healthy subjects (Part A) and subjects with moderate to severe psoriasis (Part B).
DRUGPlacebo
single SC or IV dose in healthy subjects (Part A) and subjects with moderate to severe psoriasis (Part B).
DRUG140 mg SC
single SC or IV dose in healthy subjects (Part A) and subjects with moderate to severe psoriasis (Part B).
Sponsors
Bausch Health Americas, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Part A: * Able to provide written informed consent * Healthy male or female between 18 to 45 years of age, inclusive at the time of screening * Additional inclusion criteria apply Part B: * 18 - 55 years old inclusive at Screening * Active but clinically stable, plaque psoriasis * Psoriasis involving ≥ 10% of the body surface area * A minimum PASI score of ≥ 10 obtained during the screening period * Additional inclusion criteria apply
Exclusion criteria
Part A: * History or evidence of a clinically significant disorder (including but not limited to cardiopulmonary, oncologic, renal, metabolic, hematologic or psychiatric), condition or disease that, in the opinion of the Investigator and Amgen physician would pose a risk to subject safety or interfere with the study evaluation, procedures or completion * Underlying condition that predisposes the subject to infections (eg, uncontrolled diabetes - HbA1c \> 7%, history of splenectomy) * Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part B: PASI (Psoriasis Area and Severity Index) Score Mean Percentage of Change Through Day 43 | Through day 43 | Summary of percent change in PASI (Psoriasis Area Severity Index) Scores over time by treatment groups between baseline and day 43, PASI score ranging from (0) no disease to (72) maximal disease. |
| Part B: All Treatment Adverse Events Reported for Safety Evaluation | 85 days | This primary outcome assesses number of participants iwth any reported adverse events emerging during treatment period. |
| Part A: All Treatment Adverse Events Reported for Safety Evaluation | Cohort 1-4 43 days, Cohort 5-8 64 days | This primary outcome assesses the number of participants with any reported adverse events emerging during treatment period. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Part B Single SC or IV dose of matching placebo | 5 |
| 140 mg SC Part B 140 mg Sc PsO Population | 4 |
| 350 mg SC Part B 350 mg Sc PsO population | 8 |
| 700 mg IV Part B 700 mg IV PsO population | 8 |
| Placebo Part A Single SC or IV dose of matching placebo | 14 |
| 7mg SC Part A 7mg SC PsO population | 6 |
| 21mg SC Part A 21mg SC PsO population | 6 |
| 21mg IV Part A 21mg IV PsO population | 3 |
| 70mg SC Part A 70mg SC Pso population | 6 |
| 210mg SC Part A 210mg SC PsO population | 6 |
| 210mg IV Part A 210mg IV PsO population | 4 |
| 420mg SC Part A 420mg SC PsO population | 6 |
| 700mg IV Part A 700mg IV PsO population | 6 |
| Total | 82 |
Baseline characteristics
| Characteristic | Placebo Part B | 140 mg SC Part B | 350 mg SC Part B | 700 mg IV Part B | Placebo Part A | 7mg SC Part A | 21mg SC Part A | 21mg IV Part A | 70mg SC Part A | 210mg SC Part A | 210mg IV Part A | 420mg SC Part A | 700mg IV Part A | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 45.6 years STANDARD_DEVIATION 6.6 | 34.5 years STANDARD_DEVIATION 11.7 | 39.5 years STANDARD_DEVIATION 13.4 | 43 years STANDARD_DEVIATION 11.6 | 23.1 years STANDARD_DEVIATION 2.5 | 25.5 years STANDARD_DEVIATION 8.2 | 27.0 years STANDARD_DEVIATION 8.6 | 25.3 years STANDARD_DEVIATION 2.5 | 22.2 years STANDARD_DEVIATION 1.5 | 28.3 years STANDARD_DEVIATION 9.9 | 21.3 years STANDARD_DEVIATION 2.2 | 24.5 years STANDARD_DEVIATION 6.6 | 24.3 years STANDARD_DEVIATION 3 | 32.75 years STANDARD_DEVIATION 9.05 |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants | 7 Participants | 14 Participants | 6 Participants | 6 Participants | 3 Participants | 6 Participants | 6 Participants | 4 Participants | 6 Participants | 6 Participants | 76 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 5 | 4 / 4 | 8 / 8 | 8 / 8 | 14 / 14 | 6 / 6 | 6 / 6 | 3 / 3 | 6 / 6 | 6 / 6 | 4 / 4 | 5 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 5 | 0 / 4 | 0 / 8 | 0 / 8 | 0 / 14 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Part A: All Treatment Adverse Events Reported for Safety Evaluation
This primary outcome assesses the number of participants with any reported adverse events emerging during treatment period.
Time frame: Cohort 1-4 43 days, Cohort 5-8 64 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Part A: All Treatment Adverse Events Reported for Safety Evaluation | 14 participants with events |
| 140 mg Sc | Part A: All Treatment Adverse Events Reported for Safety Evaluation | 6 participants with events |
| 350 mg Sc | Part A: All Treatment Adverse Events Reported for Safety Evaluation | 6 participants with events |
| 700 mg IV | Part A: All Treatment Adverse Events Reported for Safety Evaluation | 3 participants with events |
| Cohort 4: 70mg SC Part A | Part A: All Treatment Adverse Events Reported for Safety Evaluation | 6 participants with events |
| Cohort 5: 210mg SC Part A | Part A: All Treatment Adverse Events Reported for Safety Evaluation | 6 participants with events |
| Cohort 6: 210mg IV Part A | Part A: All Treatment Adverse Events Reported for Safety Evaluation | 4 participants with events |
| Cohort 7: 420mg SC Part A | Part A: All Treatment Adverse Events Reported for Safety Evaluation | 5 participants with events |
| Cohort 8: 700mg IV Part A | Part A: All Treatment Adverse Events Reported for Safety Evaluation | 6 participants with events |
Primary
Part B: All Treatment Adverse Events Reported for Safety Evaluation
This primary outcome assesses number of participants iwth any reported adverse events emerging during treatment period.
Time frame: 85 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Part B: All Treatment Adverse Events Reported for Safety Evaluation | 4 participants with events |
| 140 mg Sc | Part B: All Treatment Adverse Events Reported for Safety Evaluation | 3 participants with events |
| 350 mg Sc | Part B: All Treatment Adverse Events Reported for Safety Evaluation | 7 participants with events |
| 700 mg IV | Part B: All Treatment Adverse Events Reported for Safety Evaluation | 8 participants with events |
Primary
Part B: PASI (Psoriasis Area and Severity Index) Score Mean Percentage of Change Through Day 43
Summary of percent change in PASI (Psoriasis Area Severity Index) Scores over time by treatment groups between baseline and day 43, PASI score ranging from (0) no disease to (72) maximal disease.
Time frame: Through day 43
Population: This PASI outcome measure data refers only to Part B subjects with moderate to severe plaque psoriasis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Part B: PASI (Psoriasis Area and Severity Index) Score Mean Percentage of Change Through Day 43 | 19.88 percentage improvement | Standard Deviation 6.36 |
| 140 mg Sc | Part B: PASI (Psoriasis Area and Severity Index) Score Mean Percentage of Change Through Day 43 | 17.74 percentage improvement | Standard Deviation 15.34 |
| 350 mg Sc | Part B: PASI (Psoriasis Area and Severity Index) Score Mean Percentage of Change Through Day 43 | 53.57 percentage improvement | Standard Deviation 30.45 |
| 700 mg IV | Part B: PASI (Psoriasis Area and Severity Index) Score Mean Percentage of Change Through Day 43 | 86.04 percentage improvement | Standard Deviation 8.7 |