Psoriasis
Conditions
Keywords
Psoriasis
Brief summary
In this study, we will evaluate clinical activity, safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of 5 LY2525623 dosing groups compared to placebo in adults with plaque psoriasis.
Interventions
DRUGLY2525623 Intravenous
administered intravenously at randomization and every 2 weeks for 6 weeks
DRUGLY2525623 Subcutaneous
administered subcutaneously at randomization and every 2 weeks for 6 weeks
administered intravenously at randomization and every 2 weeks for 6 weeks
administered subcutaneously at randomization and every 2 weeks for 6 weeks
Sponsors
Eli Lilly and Company
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
* Are ambulatory and greater than or equal to 18 years of age. Females of child-bearing potential must test negative for pregnancy at the time of enrollment based on a serum pregnancy test and agree to use a highly reliable method of birth control as defined by those which result in a low failure rate(\<1% per year) during the study. * Chronic psoriasis vulgaris for at least 6 months prior to randomization. * Moderate and severe (plaque) psoriasis involving at least 10% body surface area (BSA) or at least 8% BSA in subjects with severe palmar-plantar involvement at randomization. * Psoriasis Area and Severity Index (PASI) total score of at least 12 at screening.
Exclusion criteria
* Have had a clinically significant flare of psoriasis during the 12 weeks prior to randomization or a biologic agent/monoclonal antibody within the longer of 5 half lives or 12 weeks prior to dosing, had systemic treatment for psoriasis or phototherapy within 4 weeks prior to dosing, or had topical psoriasis treatment within 2 weeks prior to dosing. * Have had a vaccination within 4 to 12 weeks (depending on type) prior to or intend to have one within 4 weeks after the dosing period. * Are immunocompromised or have evidence of active infection (such as viral hepatitis and/or positive testing for tuberculosis or human immunodeficiency virus \[HIV\]); or have had a recent serious systemic infection (such as mononucleosis or herpes zoster). * Have a history of or current lymphoproliferative disease or malignant disease (except for resolved cervical dysplasia; or no more than 3 successfully treated basal- or squamous- cell carcinomas of the skin), or severe drug allergies/hypersensitivity. * Have a history of serious cardiac disease within 12 weeks before randomization; or have serious or unstable/uncontrolled illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses of safety and efficacy in this study. * Have laboratory test values outside the reference range for the population or investigative site that are considered clinically significant and/or have any of the following specific abnormalities: * Aspartate transaminase (AST) or alanine transaminase (ALT) \>2 x the upper limit of normal (ULN; upper reference range of the central laboratory for the study) * Hemoglobin \<100 g/L (10 g/dL) * White blood cell (WBC) \<3.0 G/L (3,000/mm3) * Neutrophils \<1.5 G/L (1,500/mm3) * Platelets \<75 G/L (75,000/mm3) * Serum creatinine \>133 µmol/L (1.5 mg/dL) * Random glucose \>11.1mmol/L (200 mg/dL). * Have significant allergies to humanized monoclonal antibodies, or clinically significant multiple or severe drug allergies, or intolerance to topical corticosteroids
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving 75% Improvement in the Psoriasis Area and Severity Index (PASI) Scale by Week 12 | Baseline through 12 weeks | PASI combines extent of body-surface involvement assessments in 4 anatomical regions and severity of regional desquamation, erythema, and plaque induration/infiltration. Overall score: 0 (no psoriasis) to 72 (severe disease). Study BDAD was terminated after enrolling only 8 patients. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed. |
| Percent Improvement From Baseline in Psoriasis Area and Severity Index (PASI) Scale at Weeks 12 and 24 | Baseline, 12 weeks, 24 weeks | PASI combines body-surface assessments and severity of desquamation, erythema, and plaque induration/infiltration. Overall score:0(no psoriasis) to 72(severe disease). Percent(%) improvement=(baseline PASI-observed PASI)/baseline PASI\*100. Study BDAD was terminated after enrolling only 8 patients. Least Squares (LS) Mean Values were adjusted for time, treatment, and baseline. Given small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Patient's Global Assessment of Psoriasis Scale at 12 Weeks and 24 Weeks | Baseline, 12 weeks, 24 weeks | A scale measures patient perception of psoriatic condition with a continuous range of 0 (good) to 5 (severe). Study BDAD was terminated after enrolling only 8 patients. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed. |
| Change From Baseline in the Dermatology Life Quality Index (DLQI) Score at 12 Weeks | Baseline, 12 weeks | 10-item, validated questionnaire covers 6 domains. Responses range from 0 (not at all) to 3 (very much); totals range from 0 to 30 (more impairment). Study BDAD was terminated after enrolling only 8 patients. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed. |
| Change From Baseline in the 16-Item Quick Inventory for Depressive Symptomatology-Self Report (QIDS16SRTotal) at 12 Weeks | Baseline, 12 weeks | A 16-item patient-rated measure of depressive symptomatology. The total score ranges from 0 to 27 with higher scores indicative of greater severity. Study BDAD was terminated after enrolling only 8 patients. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed. |
| Change From Baseline in Relative Physician's Global Assessment (rPGA) Scale at 12 Weeks and 24 Weeks | Baseline, 12 weeks, 24 weeks | The rPGA rates the subject's psoriasis relative to baseline as 1 (100% clearing), 2 (excellent; 75%-99% clearing), 3 (good; 50%-74% clearing), 4 (fair; 25%-49% clearing), 5 (poor; 0%-24% clearing), or 6 (worsening). Study BDAD was terminated after enrolling only 8 patients. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed. |
| Pharmacokinetics: Area Under the Time Concentration Curve Through 24 Weeks | Baseline through 24 weeks | Area under the curve of serum drug concentration, including absolute bioavailability. Study BDAD was terminated after enrolling only 8 patients. Given the small sample size overall and in each treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed. |
| Number of Participants Who Developed Anti-LY2525623 Antibody Results Through 24 Weeks | Baseline through 24 weeks | Measures anti-LY2525263 antibody as positive or negative. Study BDAD was terminated after enrolling only 8 patients. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed. |
| Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) at 12 Weeks | Baseline, 12 weeks | A 14-item questionnaire with anxiety and depression subscales; 21 maximum score. Scores of 11+ on either subscale (significant case of psychological morbidity); 8-10 (borderline); 0-7 (normal). Study BDAD was terminated after enrolling only 8 patients. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed. |
| Change From Baseline in the Visual Analog Scale (VAS) for Psoriatic Arthritis at 12 Weeks and 24 Weeks | Baseline, 12 weeks, 24 weeks | A global estimate of pain caused by joint disease on arising made by the subject by placing a vertical mark or tick on a 100-mm VAS from not present to worse, range from 0 to 100mm. Study BDAD was terminated after enrolling only 8 patients. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 180 mg LY2525623 180 mg LY2525623 administered intravenously at randomization and every 2 weeks for 6 weeks | 4 |
| Subcutaneous Placebo Placebo administered subcutaneously at randomization and every 2 weeks for 6 weeks | 1 |
| 3 mg LY2525623 3 mg LY2525623 administered subcutaneously at randomization and every 2 weeks for 6 weeks | 1 |
| 30 mg LY2525623 30 mg LY2525623 administered subcutaneously at randomization and every 2 weeks for 6 weeks | 1 |
| 90 mg LY2525623 90 mg LY2525623 administered subcutaneously at randomization and every 2 weeks for 6 weeks | 1 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Sponsor Decision | 2 | 0 | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | 180 mg LY2525623 | Subcutaneous Placebo | 3 mg LY2525623 | 30 mg LY2525623 | 90 mg LY2525623 | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | 4 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 8 Participants |
| Region of Enrollment United States | 4 participants | 1 participants | 1 participants | 1 participants | 1 participants | 8 participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 6 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 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 | 3 / 4 | 0 / 1 | 0 / 1 | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 4 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 |
Outcome results
Primary
Percentage of Participants Achieving 75% Improvement in the Psoriasis Area and Severity Index (PASI) Scale by Week 12
PASI combines extent of body-surface involvement assessments in 4 anatomical regions and severity of regional desquamation, erythema, and plaque induration/infiltration. Overall score: 0 (no psoriasis) to 72 (severe disease). Study BDAD was terminated after enrolling only 8 patients. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed.
Time frame: Baseline through 12 weeks
Population: No participants had data analyzed due to the termination of the trial and the insufficient sample size.
Primary
Percent Improvement From Baseline in Psoriasis Area and Severity Index (PASI) Scale at Weeks 12 and 24
PASI combines body-surface assessments and severity of desquamation, erythema, and plaque induration/infiltration. Overall score:0(no psoriasis) to 72(severe disease). Percent(%) improvement=(baseline PASI-observed PASI)/baseline PASI\*100. Study BDAD was terminated after enrolling only 8 patients. Least Squares (LS) Mean Values were adjusted for time, treatment, and baseline. Given small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed.
Time frame: Baseline, 12 weeks, 24 weeks
Population: No participants had data analyzed due to the termination of the trial and the insufficient sample size.
Secondary
Change From Baseline in Relative Physician's Global Assessment (rPGA) Scale at 12 Weeks and 24 Weeks
The rPGA rates the subject's psoriasis relative to baseline as 1 (100% clearing), 2 (excellent; 75%-99% clearing), 3 (good; 50%-74% clearing), 4 (fair; 25%-49% clearing), 5 (poor; 0%-24% clearing), or 6 (worsening). Study BDAD was terminated after enrolling only 8 patients. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed.
Time frame: Baseline, 12 weeks, 24 weeks
Population: No participants had data analyzed due to the termination of the trial and the insufficient sample size.
Secondary
Change From Baseline in the 16-Item Quick Inventory for Depressive Symptomatology-Self Report (QIDS16SRTotal) at 12 Weeks
A 16-item patient-rated measure of depressive symptomatology. The total score ranges from 0 to 27 with higher scores indicative of greater severity. Study BDAD was terminated after enrolling only 8 patients. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed.
Time frame: Baseline, 12 weeks
Population: No participants had data analyzed due to the termination of the trial and the insufficient sample size.
Secondary
Change From Baseline in the Dermatology Life Quality Index (DLQI) Score at 12 Weeks
10-item, validated questionnaire covers 6 domains. Responses range from 0 (not at all) to 3 (very much); totals range from 0 to 30 (more impairment). Study BDAD was terminated after enrolling only 8 patients. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed.
Time frame: Baseline, 12 weeks
Population: No participants had data analyzed due to the termination of the trial and the insufficient sample size.
Secondary
Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) at 12 Weeks
A 14-item questionnaire with anxiety and depression subscales; 21 maximum score. Scores of 11+ on either subscale (significant case of psychological morbidity); 8-10 (borderline); 0-7 (normal). Study BDAD was terminated after enrolling only 8 patients. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed.
Time frame: Baseline, 12 weeks
Population: No participants had data analyzed due to the termination of the trial and the insufficient sample size.
Secondary
Change From Baseline in the Patient's Global Assessment of Psoriasis Scale at 12 Weeks and 24 Weeks
A scale measures patient perception of psoriatic condition with a continuous range of 0 (good) to 5 (severe). Study BDAD was terminated after enrolling only 8 patients. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed.
Time frame: Baseline, 12 weeks, 24 weeks
Population: No participants had data analyzed due to the termination of the trial and the insufficient sample size.
Secondary
Change From Baseline in the Visual Analog Scale (VAS) for Psoriatic Arthritis at 12 Weeks and 24 Weeks
A global estimate of pain caused by joint disease on arising made by the subject by placing a vertical mark or tick on a 100-mm VAS from not present to worse, range from 0 to 100mm. Study BDAD was terminated after enrolling only 8 patients. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed.
Time frame: Baseline, 12 weeks, 24 weeks
Population: No participants had data analyzed due to the termination of the trial and the insufficient sample size.
Secondary
Number of Participants Who Developed Anti-LY2525623 Antibody Results Through 24 Weeks
Measures anti-LY2525263 antibody as positive or negative. Study BDAD was terminated after enrolling only 8 patients. Given the small sample size overall and per treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed.
Time frame: Baseline through 24 weeks
Population: No participants had data analyzed due to the termination of the trial and the insufficient sample size.
Secondary
Pharmacokinetics: Area Under the Time Concentration Curve Through 24 Weeks
Area under the curve of serum drug concentration, including absolute bioavailability. Study BDAD was terminated after enrolling only 8 patients. Given the small sample size overall and in each treatment arm, numerical summaries and statistical comparisons are not appropriate and may be scientifically/clinically misleading; therefore, this outcome measure was not analyzed.
Time frame: Baseline through 24 weeks
Population: No participants had data analyzed due to the termination of the trial and the insufficient sample size.