Psoriasis
Conditions
Brief summary
The purpose of this study is to examine the use of a new investigational medication for the treatment of moderate plaque-type psoriasis. The study medication is rimegepant, an orally administered small molecule competitive inhibitor of the calcitonin gene-related peptide (CGRP) receptor. This medication, rimegepant, has been approved by the FDA under the trade name Nurtec for the treatment of acute migraine. However, rimegepant has not been studied in the treatment of moderate plaque-type psoriasis and is investigational for this indication.
Detailed description
This is a randomized, double-blind, placebo-controlled study of rimegepant 75 mg dosed every other day for the treatment of mild to moderate psoriasis. Subjects must have at 3% body surface area involvement before entry into the study. Psoriasis Area and Severity Index (PASI) and Investigator's Global Assessment (IGA) scores will be calculated and subjects will each complete the Dermatology Life Quality Index (DLQI) instrument as well an itch assessments. These assessments will be performed at baseline and every 2 weeks in follow-up. Areas of psoriasis in each subject will be photographed at baseline and two very similar appearing lesions identified for biopsy of one on day 1 and the other at the end of week 16. Patients will also repeat the DLQI at each visit. Subjects will also be photographed at each visit. Subjects will discontinue medications after the end of week 16. Subjects who complete the 20-week protocol will have the option of entering a 3-month, open-label extension of the study in which they will take 75 mg of rimegepant every other day for an additional 12 weeks. Eligible subjects have 2 weeks past visit 11 to enroll in the extension. For those rolling over before visit 11, visits 11 and 12 can be combined. They will have the same 7 assessments as in the previous portion of the study every 4 Protocol #20-07022368 Version Date 5/10/24 weeks including an EKG. The inclusion and exclusion criteria remain the same.
Interventions
DRUGRimegepant
Active Agent
DRUGPlacebo
Placebo Comparator
Sponsors
Pfizer
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female patients with at least 3% body surface are involved with psoriasis and a PASI score \>5. * Between 18 and 75 years of age. * Documentation of a definite diagnosis of psoriasis by a dermatologist or biopsy. * For women of childbearing potential, a negative urine pregnancy test within 48 hours of randomization. Female subjects should not have attempted to become pregnant in the month prior to exposure to rimegepant and agree not to attempt to become pregnant for 8 weeks after exposure to rimegepant. * A valid form of contraception must be documented for men and women of child-bearing potential. * The two methods for women of childbearing potential should include: * One barrier method (for example, Diaphragm with spermicidal gel, condom with spermicidal gel, cervical caps or intrauterine devices placed for at least four weeks before sexual intercourse); AND * One additional method. The other method could include hormonal contraceptives, or second barrier method as listed above. * The two options for men of childbearing potential should include: * Simultaneous use of male condom, and for the female partner, hormonal contraceptives (for example, birth control pills, implants, patch, depot injection, used since at least 4 weeks) or intra-uterine contraceptive device (placed since at least 4 weeks) before sexual intercourse; OR simultaneous use of male condom, and for the female partner, diaphragm with intravaginally applied spermicide.
Exclusion criteria
* Any ongoing medical illness or condition that places the participant at higher risk for adverse outcomes or inability to complete study procedures in the opinion of the study investigator. * Pregnancy or breastfeeding. * Known autoimmune disorders other than psoriasis. * Current use of corticosteroids or immunosuppressive medications (for any reason). * Immunodeficiency diseases. * Use of any biologic agent/monoclonal antibody within 5 half-lifes prior to baseline. * Ultraviolet light treatment, cyclosporine, oral corticosteroids, methotrexate, oral retinoids, mycophenolate mofetil, thioguanine, hydroxyurea, sirolimus or azathioprine within the 4 weeks prior to baseline or had topical psoriasis treatment within the previous 2 weeks prior to baseline. * Participation in another clinical trial involving an investigational drug within the last 30 days prior to baseline. * Inability for woman of child-bearing potential to use an effective form of contraception if sexually active. * Use of any medication that is a strong or moderate inhibitor of CYP3A, a strong or moderate inducer of CYP3A, or an inhibitor of glycoprotein (P-gp) or Breast Cancer Resistance Protein (BCRP). Please see Section 7.8 for more information. * Subject history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. Subjects with myocardial infarction (MI), acute coronary syndrome (ACS), percutaneous coronary intervention (PCI), cardiac surgery, stroke or transient ischemic attack (TIA) during 6 months (24 weeks) prior to screening. * Uncontrolled hypertension or uncontrolled diabetes (however, subjects can be included who have stable hypertension and/or diabetes for 3 months (12 weeks) prior to screening). Blood pressure greater than 150 mm Hg systolic or 100 mm Hg diastolic after 10 minutes of rest is exclusionary * Subjects with an active episode of major depressive episode within the last 6 months are ineligible. Subjects with major depressive disorder or any anxiety disorder are eligible only if they are on stable medication for each disorder for at least 3 months prior to the Screening visit. * Subject has a history or diagnosis of Gilbert's Syndrome or any other active hepatic or biliary disorder * Hematologic or solid malignancy diagnosis within 5 years prior to screening. Subjects with a history of localized basal cell or squamous cell skin cancer are eligible for the study if they are cancer-free prior to the screening visit in this study. * Subject has current diagnosis of major depressive disorder requiring treatment with atypical antipsychotics, schizophrenia, bipolar disorder, or borderline personality disorder. * History of gallstones. * Subject has current diagnosis of major depressive disorder requiring treatment with atypical antipsychotics, schizophrenia, bipolar disorder, or borderline personality disorder. * The use of CGRP antagonists (biologic \[e.g. Aimovig™, Emgality® and Ajovy™, VyeptiTM\] or small molecule \[ e.g. Ubrelvy™ {ubrogepant\]\]) other than rimegepant is prohibited during the study. * Concomitant use of atypical antipsychotics such as Abilify (aripiprazole), Zyprexa (olanzapine), Seroquel (quetiapine), Geodon (ziprasidone), or Risperdal (risperidone). * Depakote/Depakene (divalproex/valproic acid/valproate) is prohibited during the study. * Concomitant use of LAMICTAL (lamotrigine) is prohibited during the study. * Concomitant use of Modafinil (PROVIGIL®) is prohibited during the study. * Exclusionary screening lab test findings: * Serum bilirubin (Total, Direct or Indirect) \> 1 x ULN (Only abnormal values of between 1-1.5x ULN may be repeated once for assessment of eligibility prior to randomization) * AST or ALT \> 1 x ULN (Only abnormal values of between 1-1.5x ULN may be repeated once for assessment of eligibility prior to randomization) * Neutrophil count ≤ 1000/μL (or equivalent) * HbA1c \> 6.5%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Severity of Psoriasis as Measured by Percentage Change in the Psoriasis Area and Severity Index (PASI) Instrument | Baseline and Week 16 for placebo controlled trial. For Extension Phase, Visit 11/12 (Day 1) to Visit 15 (Week 12). | Total score of Psoriasis Area and Severity Index ranges from 0 to 72. Change = (Week 16 score - Baseline score) for the placebo-controlled phase and (Week 15 score-Visit 12 score) for the extension phase. A low score means less severe disease while a high score reflects more severe disease. A score of 0 means no psoriasis. A PASI score of 5 to 10 is considered moderate disease and a score over 10 is considered severe. A score over 40 is rare. The primary outcome measure is the mean percent change in PASI score from baseline to week 16 in the placebo-controlled phase. For the extension phase, it is particularly interesting if a change is noted in the group that received placebo prior to the extension phase. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Had a 50% or Greater Reduction in Psoriasis Area and Severity Index Instrument Score | Baseline and Week 16 for placebo controlled trial. For Extension Phase, Visit 11/12 (Day 1) to Visit 15 (Week 12). | To record the number of subjects whose PASI Score Improves by at least 50% by week 16 (Week 16 average score - Baseline average score) for the placebo-controled phase and the change from Visit 12 (Day 1) to Visit 15 (Week 12) for the extension phase. PASI range is 0-72 although PASI must be at least 5 for entry into the study. A score of 0 means no psoriasis. A PASI score of 5 to 10 is considered moderate disease and a score over 10 is considered severe. A score over 40 is rare. |
| Change in Severity of Psoriasis as Assessed by the Investigator's Global Assessment Instrument | Baseline and Week 16 for placebo controlled trial. For Extension Phase, Visit 11/12 (Day 1) to Week 12. | Score of the Investigator's Global Assessment instrument ranges from 0 to 5. Three parameters (erythema, induration and scaling, each is scored on a scale of 0 to 5. Erythema: 0 to 5 is the scale of intensity of erythema with 5 being the highest. Induration: 0 to 5 reflects the degree of elevation of the lesion with 5 being the most elevated. Scaling: 0 to 5 is the abundance of scale as well as the thickness and tenacious character of the scale with 5 being the most abundant, thick and tenacious scale) were each measured and averaged to obtain a score averaged to the nearest integer. The change from baseline to week 16 for each subject was calculated for the placebo-controlled phase and the change from Visit 12 to Visit 15 for the extension phase and the mean difference +/- standard deviation between groups was compared. For the extension phase, it is particularly interesting if a change is noted in the group that received placebo prior to the extension phase. |
| Change in Dermatology Quality of Life Index | Baseline and Week 16 for placebo controlled trial. For Extension Phase, Visit 11/12 (Day 1) to Visit 15 (Week 12). | Dermatology Quality of Life Index score ranges from 0-30. Average Change in Score of Each Group= (Week 16 average score - Baseline average score) for the placebo-controlled phase and (Visit 15 average score-Visit 12 average score) for the extension phase. 0 - 1 no effect at all on patient's life, 2 - 5 small effect on patient's life, 6 - 10 moderate effect on patient's life, 11 - 20 very large effect on patient's life, 21 - 30 extremely large effect on patient's life. For the extension phase, it is particularly interesting if a change is noted in the group that received placebo prior to the extension phase. |
| Change in Degree of Itching Assessed by the Visual Analogue Scale | Baseline and Week 16 for placebo controlled trial. For Extension Phase, Visit 11/12 (Day 1) to Week 12. | The Visual Analogue Scale ranges from 0 to 10. 0= no pruritus, \< 3= mild pruritus, ≥ 3-\<7= moderate pruritus, ≥ 7-\<9 = severe pruritus, ≥ 9= very severe pruritus. We separately measured the reduction in average itch over the preceding 3 days and the reduction in maximum itch over the previous 7 days for each subject. For the extension phase, it is particularly interesting if a change is noted in the group that received placebo prior to the extension phase. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the dermatology practices of the Weill Cornell Medical College Department of Dermatology and the practice of Neil Sadick, M.D., a voluntary faculty member of the department.
Pre-assignment details
Ninety-six subjects were screened, 41 met criteria for entry. Five subjects withdrew or were withdrawn before being assigned to a group.
Participants by arm
| Arm | Count |
|---|---|
| Rimegepant Participants receive a rimegepant 75 mg tablet orally every other day for 16 weeks.
Rimegepant: Active Agent | 18 |
| Placebo Participants receive a placebo tablet matching rimegepant orally every other day for 16 weeks.
Placebo: Placebo Comparator | 18 |
| Rimegepant Extension-Previously Received Rimegepant-Open Label Participants who previously received rimegepant receive a rimegepant 75 mg tablet orally every other day for an additional 12 weeks.
Rimegepant: Active Agent | 12 |
| Rimegepant Extension-Previously Received Placebo-Open Label Participants who previously received placebo receive a rimegepant 75 mg tablet orally every other day for an additional 12 weeks.
Rimegepant: Active Agent | 6 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-Blind Placebo Controlled Trial | Adverse Event | 0 | 2 | 0 | 0 |
| Double-Blind Placebo Controlled Trial | Lost to Follow-up | 1 | 1 | 0 | 0 |
| Double-Blind Placebo Controlled Trial | Withdrawal by Subject | 0 | 2 | 0 | 0 |
| Extension Study | Adverse Event | 0 | 0 | 0 | 1 |
| Extension Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Rimegepant | Total | Placebo | Rimegepant Extension-Previously Received Rimegepant-Open Label | Rimegepant Extension-Previously Received Placebo-Open Label |
|---|---|---|---|---|---|
| Age, Continuous Double-Blind Controlled Trial | 47.72 years STANDARD_DEVIATION 14.85 | 49.29 years STANDARD_DEVIATION 14.37 | 50.94 years STANDARD_DEVIATION 14.09 | — | — |
| Age, Continuous Open Label Extension | — | 47.72 years STANDARD_DEVIATION 14.34 | — | 48.42 years STANDARD_DEVIATION 15.29 | 46.33 years STANDARD_DEVIATION 13.49 |
| Ethnicity (NIH/OMB) Double-Blind Controlled Trial Hispanic or Latino | 6 Participants | 13 Participants | 7 Participants | — | — |
| Ethnicity (NIH/OMB) Double-Blind Controlled Trial Not Hispanic or Latino | 12 Participants | 22 Participants | 10 Participants | — | — |
| Ethnicity (NIH/OMB) Double-Blind Controlled Trial Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | — | — |
| Ethnicity (NIH/OMB) Open Label Extension Hispanic or Latino | — | 5 Participants | — | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Open Label Extension Not Hispanic or Latino | — | 13 Participants | — | 9 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Open Label Extension Unknown or Not Reported | — | 0 Participants | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Double-Blind Controlled Trial American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Double-Blind Controlled Trial Asian | 1 Participants | 3 Participants | 2 Participants | — | — |
| Race (NIH/OMB) Double-Blind Controlled Trial Black or African American | 1 Participants | 2 Participants | 1 Participants | — | — |
| Race (NIH/OMB) Double-Blind Controlled Trial More than one race | 0 Participants | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Double-Blind Controlled Trial Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Double-Blind Controlled Trial Unknown or Not Reported | 5 Participants | 10 Participants | 5 Participants | — | — |
| Race (NIH/OMB) Double-Blind Controlled Trial White | 11 Participants | 21 Participants | 10 Participants | — | — |
| Race (NIH/OMB) Open Label Extension American Indian or Alaska Native | — | 0 Participants | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Open Label Extension Asian | — | 2 Participants | — | 1 Participants | 1 Participants |
| Race (NIH/OMB) Open Label Extension Black or African American | — | 1 Participants | — | 0 Participants | 1 Participants |
| Race (NIH/OMB) Open Label Extension More than one race | — | 0 Participants | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Open Label Extension Native Hawaiian or Other Pacific Islander | — | 0 Participants | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Open Label Extension Unknown or Not Reported | — | 4 Participants | — | 4 Participants | 0 Participants |
| Race (NIH/OMB) Open Label Extension White | — | 11 Participants | — | 7 Participants | 4 Participants |
| Region of Enrollment United States | 18 participants | 36 participants | 18 participants | 12 participants | 6 participants |
| Sex: Female, Male Double-Blind Controlled Trial Female | 6 Participants | 12 Participants | 6 Participants | — | — |
| Sex: Female, Male Double-Blind Controlled Trial Male | 12 Participants | 24 Participants | 12 Participants | — | — |
| Sex: Female, Male Open Label Extension Female | — | 6 Participants | — | 3 Participants | 3 Participants |
| Sex: Female, Male Open Label Extension Male | — | 12 Participants | — | 9 Participants | 3 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 / 18 | 0 / 18 | 0 / 12 | 0 / 6 |
| other Total, other adverse events | 1 / 18 | 4 / 18 | 1 / 12 | 2 / 6 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 12 | 0 / 6 |
Outcome results
Primary
Change in Severity of Psoriasis as Measured by Percentage Change in the Psoriasis Area and Severity Index (PASI) Instrument
Total score of Psoriasis Area and Severity Index ranges from 0 to 72. Change = (Week 16 score - Baseline score) for the placebo-controlled phase and (Week 15 score-Visit 12 score) for the extension phase. A low score means less severe disease while a high score reflects more severe disease. A score of 0 means no psoriasis. A PASI score of 5 to 10 is considered moderate disease and a score over 10 is considered severe. A score over 40 is rare. The primary outcome measure is the mean percent change in PASI score from baseline to week 16 in the placebo-controlled phase. For the extension phase, it is particularly interesting if a change is noted in the group that received placebo prior to the extension phase.
Time frame: Baseline and Week 16 for placebo controlled trial. For Extension Phase, Visit 11/12 (Day 1) to Visit 15 (Week 12).
Population: The number of subjects in each arm of the extension phase of our study are a subset of the subjects treated in the double blind, placebo controlled initial phase of the study. Furthermore, one subject assigned to the placebo group was not included in the analysis due to having an adverse reaction (very severe insect bite reaction) prior to the first scheduled evaluation. Thus, the total number of analyzed subjects in the placebo-controlled phase was 35.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rimegepant | Change in Severity of Psoriasis as Measured by Percentage Change in the Psoriasis Area and Severity Index (PASI) Instrument | 17.29 Percent change in PASI score | Standard Deviation 34.43 |
| Placebo | Change in Severity of Psoriasis as Measured by Percentage Change in the Psoriasis Area and Severity Index (PASI) Instrument | 27.06 Percent change in PASI score | Standard Deviation 32.58 |
| Rimegepant Extension-Previously Received Rimegepant-Open Label | Change in Severity of Psoriasis as Measured by Percentage Change in the Psoriasis Area and Severity Index (PASI) Instrument | 7.07 Percent change in PASI score | Standard Deviation 31.68 |
| Rimegepant Extension-Previously Received Placebo-Open Label | Change in Severity of Psoriasis as Measured by Percentage Change in the Psoriasis Area and Severity Index (PASI) Instrument | 20.02 Percent change in PASI score | Standard Deviation 28.78 |
p-value: 0.395t-test, 2 sided
p-value: 0.41t-test, 2 sided
Secondary
Change in Degree of Itching Assessed by the Visual Analogue Scale
The Visual Analogue Scale ranges from 0 to 10. 0= no pruritus, \< 3= mild pruritus, ≥ 3-\<7= moderate pruritus, ≥ 7-\<9 = severe pruritus, ≥ 9= very severe pruritus. We separately measured the reduction in average itch over the preceding 3 days and the reduction in maximum itch over the previous 7 days for each subject. For the extension phase, it is particularly interesting if a change is noted in the group that received placebo prior to the extension phase.
Time frame: Baseline and Week 16 for placebo controlled trial. For Extension Phase, Visit 11/12 (Day 1) to Week 12.
Population: The number of subjects in each arm of the extension phase of our study are a subset of the subjects treated in the double blind, placebo controlled initial phase of the study. Furthermore, one subject assigned to the placebo group was not included in the analysis due to having an adverse reaction (very severe insect bite reaction) prior to the first scheduled evaluation. Thus, the total number of analyzed subjects in the placebo-controlled phase was 35.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rimegepant | Change in Degree of Itching Assessed by the Visual Analogue Scale | Mean reduction in average itch | 0.76 score on a scale | Standard Deviation 2.64 |
| Rimegepant | Change in Degree of Itching Assessed by the Visual Analogue Scale | Mean reduction max itch | 0.93 score on a scale | Standard Deviation 2.97 |
| Placebo | Change in Degree of Itching Assessed by the Visual Analogue Scale | Mean reduction in average itch | 2.05 score on a scale | Standard Deviation 3.06 |
| Placebo | Change in Degree of Itching Assessed by the Visual Analogue Scale | Mean reduction max itch | 1.86 score on a scale | Standard Deviation 2.81 |
| Rimegepant Extension-Previously Received Rimegepant-Open Label | Change in Degree of Itching Assessed by the Visual Analogue Scale | Mean reduction max itch | 0.43 score on a scale | Standard Deviation 2.08 |
| Rimegepant Extension-Previously Received Rimegepant-Open Label | Change in Degree of Itching Assessed by the Visual Analogue Scale | Mean reduction in average itch | 0.58 score on a scale | Standard Deviation 2.01 |
| Rimegepant Extension-Previously Received Placebo-Open Label | Change in Degree of Itching Assessed by the Visual Analogue Scale | Mean reduction max itch | -0.02 score on a scale | Standard Deviation 1.09 |
| Rimegepant Extension-Previously Received Placebo-Open Label | Change in Degree of Itching Assessed by the Visual Analogue Scale | Mean reduction in average itch | -0.07 score on a scale | Standard Deviation 1.02 |
Comparison: Mean Reduction in Average Itchp-value: 0.192t-test, 2 sided
Comparison: Mean Reduction in Average Itch. Data represent change values.p-value: 0.392t-test, 2 sided
Comparison: Mean Reduction in Maximum Itchp-value: 0.347t-test, 2 sided
Comparison: Mean Reduction in Maximum Itch. Data represent change values.p-value: 0.572t-test, 2 sided
Secondary
Change in Dermatology Quality of Life Index
Dermatology Quality of Life Index score ranges from 0-30. Average Change in Score of Each Group= (Week 16 average score - Baseline average score) for the placebo-controlled phase and (Visit 15 average score-Visit 12 average score) for the extension phase. 0 - 1 no effect at all on patient's life, 2 - 5 small effect on patient's life, 6 - 10 moderate effect on patient's life, 11 - 20 very large effect on patient's life, 21 - 30 extremely large effect on patient's life. For the extension phase, it is particularly interesting if a change is noted in the group that received placebo prior to the extension phase.
Time frame: Baseline and Week 16 for placebo controlled trial. For Extension Phase, Visit 11/12 (Day 1) to Visit 15 (Week 12).
Population: The number of subjects in each arm of the extension phase of our study are a subset of the subjects treated in the double blind, placebo controlled initial phase of the study. Furthermore, one subject assigned to the placebo group was not included in the analysis due to having an adverse reaction (very severe insect bite reaction) prior to the first scheduled evaluation. Thus, the total number of analyzed subjects in the placebo-controlled phase was 35.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rimegepant | Change in Dermatology Quality of Life Index | 2.22 score on a scale | Standard Deviation 5.15 |
| Placebo | Change in Dermatology Quality of Life Index | 4.65 score on a scale | Standard Deviation 8.4 |
| Rimegepant Extension-Previously Received Rimegepant-Open Label | Change in Dermatology Quality of Life Index | 1.45 score on a scale | Standard Deviation 5.28 |
| Rimegepant Extension-Previously Received Placebo-Open Label | Change in Dermatology Quality of Life Index | 0.5 score on a scale | Standard Deviation 2.07 |
p-value: 0.316t-test, 2 sided
Comparison: Data represent change values.p-value: 0.605t-test, 2 sided
Secondary
Change in Severity of Psoriasis as Assessed by the Investigator's Global Assessment Instrument
Score of the Investigator's Global Assessment instrument ranges from 0 to 5. Three parameters (erythema, induration and scaling, each is scored on a scale of 0 to 5. Erythema: 0 to 5 is the scale of intensity of erythema with 5 being the highest. Induration: 0 to 5 reflects the degree of elevation of the lesion with 5 being the most elevated. Scaling: 0 to 5 is the abundance of scale as well as the thickness and tenacious character of the scale with 5 being the most abundant, thick and tenacious scale) were each measured and averaged to obtain a score averaged to the nearest integer. The change from baseline to week 16 for each subject was calculated for the placebo-controlled phase and the change from Visit 12 to Visit 15 for the extension phase and the mean difference +/- standard deviation between groups was compared. For the extension phase, it is particularly interesting if a change is noted in the group that received placebo prior to the extension phase.
Time frame: Baseline and Week 16 for placebo controlled trial. For Extension Phase, Visit 11/12 (Day 1) to Week 12.
Population: The number of subjects in each arm of the extension phase of our study are a subset of the subjects treated in the double blind, placebo controlled initial phase of the study. Furthermore, one subject assigned to the placebo group was not included in the analysis due to having an adverse reaction (very severe insect bite reaction) prior to the first scheduled evaluation. Thus, the total number of analyzed subjects in the placebo-controlled phase was 35.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rimegepant | Change in Severity of Psoriasis as Assessed by the Investigator's Global Assessment Instrument | 0.39 score on a scale | Standard Deviation 0.98 |
| Placebo | Change in Severity of Psoriasis as Assessed by the Investigator's Global Assessment Instrument | 0.47 score on a scale | Standard Deviation 0.51 |
| Rimegepant Extension-Previously Received Rimegepant-Open Label | Change in Severity of Psoriasis as Assessed by the Investigator's Global Assessment Instrument | 0.18 score on a scale | Standard Deviation 0.4 |
| Rimegepant Extension-Previously Received Placebo-Open Label | Change in Severity of Psoriasis as Assessed by the Investigator's Global Assessment Instrument | 0.5 score on a scale | Standard Deviation 0.55 |
p-value: 0.758t-test, 2 sided
Comparison: Data represent change values.p-value: 0.247Fisher Exact
Secondary
Number of Subjects Who Had a 50% or Greater Reduction in Psoriasis Area and Severity Index Instrument Score
To record the number of subjects whose PASI Score Improves by at least 50% by week 16 (Week 16 average score - Baseline average score) for the placebo-controled phase and the change from Visit 12 (Day 1) to Visit 15 (Week 12) for the extension phase. PASI range is 0-72 although PASI must be at least 5 for entry into the study. A score of 0 means no psoriasis. A PASI score of 5 to 10 is considered moderate disease and a score over 10 is considered severe. A score over 40 is rare.
Time frame: Baseline and Week 16 for placebo controlled trial. For Extension Phase, Visit 11/12 (Day 1) to Visit 15 (Week 12).
Population: The number of subjects in each arm of the extension phase of our study are a subset of the subjects treated in the double blind, placebo controlled initial phase of the study. Furthermore, one subject assigned to the placebo group was not included in the analysis due to having an adverse reaction (very severe insect bite reaction) prior to the first scheduled evaluation. Thus, the total number of analyzed subjects in the placebo-controlled phase was 35.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rimegepant | Number of Subjects Who Had a 50% or Greater Reduction in Psoriasis Area and Severity Index Instrument Score | 3 Participants |
| Placebo | Number of Subjects Who Had a 50% or Greater Reduction in Psoriasis Area and Severity Index Instrument Score | 4 Participants |
| Rimegepant Extension-Previously Received Rimegepant-Open Label | Number of Subjects Who Had a 50% or Greater Reduction in Psoriasis Area and Severity Index Instrument Score | 1 Participants |
| Rimegepant Extension-Previously Received Placebo-Open Label | Number of Subjects Who Had a 50% or Greater Reduction in Psoriasis Area and Severity Index Instrument Score | 0 Participants |
p-value: 0.691Fisher Exact
p-value: 1Fisher Exact
Post Hoc
Change in Degree of Itching Assessed by the Visual Analogue Scale From Visit 11/12 to Visit 15 in the Extension Phase - Previously Received Placebo Group
The Visual Analogue Scale ranges from 0 to 10. 0= no pruritus, \< 3= mild pruritus, ≥ 3-\<7= moderate pruritus, ≥ 7-\<9 = severe pruritus, ≥ 9= very severe pruritus. We separately measured the reduction in average itch over the preceding 3 days and the reduction in maximum itch over the previous 7 days for each subject. Have examined the change in each score from visit 11/12 to visit 15 in the extension phase.
Time frame: Visit 11/12 (Day 1) to Visit 15 (Week 12).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rimegepant | Change in Degree of Itching Assessed by the Visual Analogue Scale From Visit 11/12 to Visit 15 in the Extension Phase - Previously Received Placebo Group | Average Itch Preceding 3 Days | 0.05 score on a scale |
| Rimegepant | Change in Degree of Itching Assessed by the Visual Analogue Scale From Visit 11/12 to Visit 15 in the Extension Phase - Previously Received Placebo Group | Maximum Itch Within the Preceding 7 Days | 0 score on a scale |
Comparison: Analysis for Average Itch Over the Preceding 3 Daysp-value: 1Wilcoxon (Mann-Whitney)
Comparison: Analysis is for the Maximum Itch of the Preceding 7 Daysp-value: 1Wilcoxon (Mann-Whitney)
Post Hoc
Change in Degree of Itching Assessed by the Visual Analogue Scale From Visit 11/12 to Visit 15 in the Extension Phase - Previously Received Rimegepant Group
The Visual Analogue Scale ranges from 0 to 10. 0= no pruritus, \< 3= mild pruritus, ≥ 3-\<7= moderate pruritus, ≥ 7-\<9 = severe pruritus, ≥ 9= very severe pruritus. We separately measured the reduction in average itch over the preceding 3 days and the reduction in maximum itch over the previous 7 days for each subject. Have examined the change in each score from visit 11/12 to visit 15 in the extension phase.
Time frame: Visit 11/12 (Day 1) to Visit 15 (Week 12).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rimegepant | Change in Degree of Itching Assessed by the Visual Analogue Scale From Visit 11/12 to Visit 15 in the Extension Phase - Previously Received Rimegepant Group | Average Itch Preceding 3 Days | 0.6 score on a scale |
| Rimegepant | Change in Degree of Itching Assessed by the Visual Analogue Scale From Visit 11/12 to Visit 15 in the Extension Phase - Previously Received Rimegepant Group | Maximum Itch Within the Preceding 7 days | 0.4 score on a scale |
Comparison: Analysis for Average Itch Over the Preceding 3 Daysp-value: 0.221Wilcoxon (Mann-Whitney)
Comparison: Analysis is for the Maximum Itch of the Preceding 7 Daysp-value: 0.286Wilcoxon (Mann-Whitney)
Post Hoc
Change in Severity of Psoriasis as Assessed by the Investigator's Global Assessment Instrument From Visit 11/12 to Visit 15 in the Extension Phase - Previously Received Placebo Group
Score of the Investigator's Global Assessment instrument ranges from 0 to 5. Three parameters (erythema, induration and scaling, each is scored on a scale of 0 to 5. Erythema: 0 to 5 is the scale of intensity of erythema with 5 being the highest. Induration: 0 to 5 reflects the degree of elevation of the lesion with 5 being the most elevated. Scaling: 0 to 5 is the abundance of scale as well as the thickness and tenacious character of the scale with 5 being the most abundant, thick and tenacious scale) were each measured and averaged to obtain a score averaged to the nearest integer. The change from Visit 11/12 to Visit 15 for the extension phase was examined.
Time frame: Visit 11/12 (Day 1) to Visit 15 (Week 12).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rimegepant | Change in Severity of Psoriasis as Assessed by the Investigator's Global Assessment Instrument From Visit 11/12 to Visit 15 in the Extension Phase - Previously Received Placebo Group | 0.5 score on a scale |
p-value: 0.149Wilcoxon (Mann-Whitney)
Post Hoc
Change in Severity of Psoriasis as Assessed by the Investigator's Global Assessment Instrument From Visit 11/12 to Visit 15 in the Extension Phase - Previously Received Rimegepant Group
Score of the Investigator's Global Assessment instrument ranges from 0 to 5. Three parameters (erythema, induration and scaling, each is scored on a scale of 0 to 5. Erythema: 0 to 5 is the scale of intensity of erythema with 5 being the highest. Induration: 0 to 5 reflects the degree of elevation of the lesion with 5 being the most elevated. Scaling: 0 to 5 is the abundance of scale as well as the thickness and tenacious character of the scale with 5 being the most abundant, thick and tenacious scale) were each measured and averaged to obtain a score averaged to the nearest integer. The change from Visit 11/12 to Visit 15 for the extension phase was examined.
Time frame: Visit 11/12 (Day 1) to Visit 15 (Week 12).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rimegepant | Change in Severity of Psoriasis as Assessed by the Investigator's Global Assessment Instrument From Visit 11/12 to Visit 15 in the Extension Phase - Previously Received Rimegepant Group | 0 score on a scale |
p-value: 0.346Wilcoxon (Mann-Whitney)
Post Hoc
Median Change in the Dermatology Life Quality Index (DLQI) Instrument Score From Visit 11/12 to Visit 15 in the Extension Phase - Previously Received Placebo Group
Dermatology Quality of Life Index score ranges from 0-30. . 0 - 1 no effect at all on patient's life, 2 - 5 small effect on patient's life, 6 - 10 moderate effect on patient's life, 11 - 20 very large effect on patient's life, 21 - 30 extremely large effect on patient's life. Change in Median Score of Each Group = (Visit 15 median score-Visit 11/12 median score) for the extension phase was examined
Time frame: Visit 11/12 (Day 1) to Visit 15 (Week 12).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rimegepant | Median Change in the Dermatology Life Quality Index (DLQI) Instrument Score From Visit 11/12 to Visit 15 in the Extension Phase - Previously Received Placebo Group | 0.5 score on a scale |
p-value: 0.713Wilcoxon (Mann-Whitney)
Post Hoc
Median Change in the Dermatology Life Quality Index (DLQI) Instrument Score From Visit 11/12 to Visit 15 in the Extension Phase - Previously Received Rimegepant Group
Dermatology Quality of Life Index score ranges from 0-30. . 0 - 1 no effect at all on patient's life, 2 - 5 small effect on patient's life, 6 - 10 moderate effect on patient's life, 11 - 20 very large effect on patient's life, 21 - 30 extremely large effect on patient's life. Change in Median Score of Each Group = (Visit 15 median score-Visit 11/12 median score) for the extension phase was examined
Time frame: Visit 11/12 (Day 1) to Visit 15 (Week 12).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rimegepant | Median Change in the Dermatology Life Quality Index (DLQI) Instrument Score From Visit 11/12 to Visit 15 in the Extension Phase - Previously Received Rimegepant Group | 0 score on a scale |
p-value: 0.582Wilcoxon (Mann-Whitney)
Post Hoc
Median Change in the Psoriasis Area and Severity Index (PASI) Instrument Score From Visit 11/12 to Visit 15 in the Extension Phase - Previously Received Placebo Group
Total score of Psoriasis Area and Severity Index ranges from 0 to 72. A low score means less severe disease while a high score reflects more severe disease. A score of 0 means no psoriasis. A PASI score of 5 to 10 is considered moderate disease and a score over 10 is considered severe. A score over 40 is rare. Change = (Week 15 score-Visit 12 score) for the extension phase was examined.
Time frame: Visit 11/12 (Day 1) to Visit 15 (Week 12).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rimegepant | Median Change in the Psoriasis Area and Severity Index (PASI) Instrument Score From Visit 11/12 to Visit 15 in the Extension Phase - Previously Received Placebo Group | 1.35 score on a scale |
p-value: 0.141Wilcoxon (Mann-Whitney)
Post Hoc
Median Change in the Psoriasis Area and Severity Index (PASI) Instrument Score From Visit 11/12 to Visit 15 in the Extension Phase - Previously Received Rimegepant Group
Total score of Psoriasis Area and Severity Index ranges from 0 to 72. A low score means less severe disease while a high score reflects more severe disease. A score of 0 means no psoriasis. A PASI score of 5 to 10 is considered moderate disease and a score over 10 is considered severe. A score over 40 is rare. Change = (Week 15 score-Visit 12 score) for the extension phase was examined.
Time frame: Visit 11/12 (Day 1) to Visit 15 (Week 12).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rimegepant | Median Change in the Psoriasis Area and Severity Index (PASI) Instrument Score From Visit 11/12 to Visit 15 in the Extension Phase - Previously Received Rimegepant Group | 0.9 score on a scale |
p-value: 0.359Wilcoxon (Mann-Whitney)