Conditions: Psoriasis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 41
Healthy volunteers: no

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.

Arms:
arm 1: Participants receive a rimegepant 75 mg tablet orally every other day for 16 weeks. arm 2: Participants receive a placebo tablet matching rimegepant orally every other day for 16 weeks. arm 3: Participants who previously received rimegepant receive a rimegepant 75 mg tablet orally every other day for an additional 12 weeks.

Rimegepant: Active Agent arm 4: Participants who previously received placebo receive a rimegepant 75 mg tablet orally every other day for an additional 12 weeks.

Rimegepant: Active Agent

Interventions: intervention 1: Rimegepant intervention 2: Placebo
Intervention descriptions: intervention 1: Active Agent intervention 2: Placebo Comparator

Protocol document:
Prot_SAP_000.pdf: 
TITLE: A Pilot Study of Rimegepant in Moderate Plaque-type Psoriasis
 
 
 
     NCT Number:  NCT04629950 
      
 
                   Document Date:  5/10/2024


Protocol #20-07022368 
Version Date 5/10/24 
TITLE: A Pilot Study of Rimegepant in Moderate Plaque-type Psoriasis 
IRB Protocol #: 20-07022368 
IND/IDE #: 152321 
Version Date: 10 May 2024 
Funding Source(s): Pfizer, Inc. 
Principal Investigator: 
Name. 
Richard D. Granstein, MD 
Address 
WGC 9 
Telephone 
(646) 962-7546
Fax 
(646) 962-0033
E-mail address 
rdgranst@med.cornell.edu
Co-Investigators: 
Name 
Address 
Telephone 
Fax 
Jennifer Vu, PA 
WGC 9 
(646) 962-7275
(646) 962-0033
E-mail address 
jtv4002@med.cornell.edu
Name 
Morgan Lynch, PA-C 
Address 
WGC 9 
Telephone 
(646) 962-5565
Fax 
(646) 962-0033
E-mail address 
mol9034@med.cornell.edu
Name 
Neil Sadick, MD 
Address 
911 Park Ave. New York, NY 
Telephone 
(212) 772-7242
Fax 
(917) 768-7236
E-mail address 
nssderm@sadickdermatology.com
Statistician: 
Medical Monitor: 
Name 
Kathy Xi Zhou, PhD 
Name 
Steven Cohen, MD 
Address 
402 E. 67th St., New York, NY 10065 
Address 
WGC 9 
Telephone 
(646) 962-8027
Telephone 
(646) 962-3376
Fax 
(646) 962-0280
Fax 
(646) 962-0033
E-mail address kaz2004@med.cornell.edu
E-mail address src4005@med.cornell.edu
Participating Sites: Weill Cornell Medicine, Sadick Dermatology 


Protocol #20-07022368 
Version Date 5/10/2024 
 
2 
 
 
Table of Contents 
CONFIDENTIALITY STATEMENT ....................................................................................................... 5 
LIST OF ABBREVIATIONS................................................................................................................... 6 
1. PROTOCOL SUMMARY ................................................................................................................... 7 
1.1 
Schema ...................................................................................................................................... 9 
1.2 
Study Objectives and End Points ...................................................................................... 10 
1.2.1 
Primary Objectives .................................................................................................... 10 
1.2.2 
Secondary Objectives ............................................................................................... 10 
1.2.3 
Exploratory Objectives ............................................................................................. 10 
1.2.4 
Primary Endpoints ..................................................................................................... 10 
1.2.5 
Secondary Endpoints ............................................................................................... 10 
2. BACKGROUND ............................................................................................................................... 11 
2.1 
Disease ................................................................................................................................... 11 
2.2 
Investigational Agent/Device, or Surgical Treatment/Method ......................................... 11 
2.3 
Rationale ................................................................................................................................ 12 
2.4 
Risk/Benefit Assessment .................................................................................................... 12 
2.4.1 
Known Potential Risks .............................................................................................. 12 
2.4.2 
Known Potential Benefits ......................................................................................... 13 
2.4.3 
Assessment of Potential Risks and Benefits ........................................................ 13 
2.5 
Correlative Studies Background ......................................................................................... 13 
3. STUDY DESIGN .............................................................................................................................. 13 
3.1 
Overall Design ....................................................................................................................... 13 
3.2 
Justification for Dose ........................................................................................................... 14 
3.3 
End of Study Definition ........................................................................................................ 14 
4. SUBJECT SELECTION .................................................................................................................. 14 
4.1 
Study Population................................................................................................................... 14 
4.2 
Inclusion Criteria ................................................................................................................... 14 
4.3 
Exclusion Criteria ................................................................................................................. 15 
4.4 
Lifestyle Considerations....................................................................................................... 16 
4.5 
Screen Failures ..................................................................................................................... 16 
4.6 
Strategies for Recruitment and Retention ......................................................................... 16 
5. REGISTRATION PROCEDURES ................................................................................................... 17 
5.1 
Subject Registration (WCM only) ........................................................................................ 17 
5.2 Subject Registration (Sub-sites) ............................................................................................. 17 
6. STUDY PROCEDURES................................................................................................................... 17 
6.1 
Schedule of Assessments ................................................................................................... 17 
6.1.1 
Screening Visit (-X days before start of treatment) .............................................. 19 
6.1.2 
Treatment Phase........................................................................................................ 18 
6.1.2.1 
Visit 1 (baseline; Cycle 1 Day 1) .............................................................................. 18 
6.1.2.2 
Visit 2 (± X day(s))...................................................................................................... 20 
6.1.3 
Follow-up Phase ........................................................................................................ 20 
7. STUDY INTERVENTION ................................................................................................................. 20 


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7.2 
Availability ............................................................................................................................. 20 
7.3 
Acquisition and Accountability .......................................................................................... 20 
7.4 
Formulation, Appearance, Packaging, and Labeling ....................................................... 21 
7.5 
Product Storage and Stability ............................................................................................ 21 
7.6 
Preparation............................................................................................................................ 21 
7.7 
Dosing and Administration ................................................................................................. 21 
7.7.1 
Dosing Delays/Dose Modifications ......................................................................... 21 
7.8 
General Concomitant Medication and Supportive Care Guidelines .............................. 21 
7.9 
Duration of Therapy and Criteria for Removal from Study ............................................. 23 
7.10 Duration of Follow Up ........................................................................................................... 22 
7.11 Measures to Minimize Bias: Randomization and Blinding ................................................ 22 
7.12 Study Intervention/Follow-up Compliance .......................................................................... 24 
8. STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ...............................................................................................24 
8.1 
Discontinuation of Study Intervention ............................................................................... 24 
8.2 
Participant Discontinuation/Withdrawal from the Study ................................................. 25 
8.3 
Lost to Follow Up ................................................................................................................. 25 
9. CORRELATIVE/SPECIAL STUDIES ............................................................................................. 26 
10. MEASUREMENT OF EFFECT ...................................................................................................26 
10.1 Response Criteria ................................................................................................................... 26 
10.2 Duration of Response ............................................................................................................ 26 
10.3 Progression-Free Survival ..................................................................................................... 26 
10.4 Other Response Parameters ................................................................................................. 26 
11. DATA REPORTING / REGULATORY CONSIDERATIONS ..................................................... 26 
11.1 Data Collection ........................................................................................................................ 26 
11.1.1 REDCap ............................................................................................................................. 26 
11.2 Regulatory Considerations .................................................................................................... 26 
11.2.1 Institutional Review Board/Ethics Committee Approval ............................................. 26 
11.2.2 Ethical Conduct of the Study ......................................................................................... 27 
11.2.3 Informed Consent ............................................................................................................ 28 
11.2.4 Compliance with Trial Registration and Results Posting Requirements ................. 28 
11.2.5 Record Retention ............................................................................................................. 28 
12. STATISTICAL CONSIDERATIONS ........................................................................................... 28 
12.1 Study Design/Endpoints ........................................................................................................ 28 
12.2 Sample Size/Accrual Rate ...................................................................................................... 28 
12.3 Stratification Factors .............................................................................................................. 29 
12.4 Analysis of Endpoints ............................................................................................................. 29 
12.4.1 
Analysis of Primary Endpoints ................................................................................ 29 
12.4.2 
Analysis of Secondary Endpoints ........................................................................... 29 
12.5 Interim Analysis ....................................................................................................................... 30 
12.6 Reporting and Exclusions ...................................................................................................... 30 
12.6.1 
Evaluation of Toxicity ............................................................................................... 30 
12.6.2 
Evaluation of Response ........................................................................................... 30 
13. ADVERSE EVENT REPORTING REQUIREMENTS ..................................................................30 
13.1 Adverse Event Definition........................................................................................................ 30 


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13.1.2 
Adverse Event Characteristics and Related Attributions .................................... 31 
13.1.3 
Recording of Adverse Events .................................................................................. 31 
13.1.4 
Reporting of AE to WCM IRB ................................................................................... 31 
13.1.5 
Reporting Events to Participants ............................................................................ 31 
13.1.6 
Events of Special Interest ........................................................................................ 31 
13.1.7 
Reporting of Pregnancy ........................................................................................... 31 
13.2 Definition of SAE ..................................................................................................................... 32 
13.2.1 
Reporting of SAE to IRB .......................................................................................... 32 
13.2.2 
Reporting of SAE to FDA [For Protocols Where WCMC is the Sponsor- 
Investigator] ................................................................................................................................. 32 
13.2.3 
Reporting of SAE to Pfizer, Inc ................................................................................ 33 
13.3 AE/SAE Follow Up .................................................................................................................. 34 
13.4 Time Period and Frequency for Event Assessment and Follow Up ................................. 34 
14. UNANTICIPATED PROBLEMS INVOLVING RISKS TO SUBJECTS OR OTHERS ...............34 
14.1 Definition of Unanticipated Problems Involving Risks to Subjects or Others 
(UPIRTSO) ........................................................................................................................................ 34 
14.1.2 
Unanticipated Problem Reporting .......................................................................... 35 
15. DATA AND SAFETY MONITORING PLAN (DSMP) ..................................................................35 
16. REFERENCES .............................................................................................................................38 


Protocol #20-07022368 
Version Date 5/10/24 
5 
 
 
Statement of Compliance 
 
 
(1) [The trial will be carried out in accordance with International Conference on Harmonization 
Good Clinical Practice (ICH GCP) and the following 
 
 
• 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies 
(45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR 
Part 812) 
 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials 
will be submitted to the Institutional Review Board (IRB) for review and approval. 
Approval of both the protocol and the consent form must be obtained before any 
participant is enrolled. Any amendment to the protocol will require review and approval by 
the IRB before the changes are implemented to the study. In addition, all changes to the 
consent form will be IRB-approved; a determination will be made regarding whether a new 
consent needs to be obtained from participants who provided consent, using a previously 
approved consent form.] 
 
 
 
 
Confidentiality Statement 
 
This document is confidential and is to be distributed for review only to investigators, potential 
investigators, consultants, study staff, and applicable independent ethics committees or 
institutional review boards. The contents of this document shall not be disclosed to others without 
written authorization from WCM, unless disclosure on ClinicalTrials.gov is federally required. 
 
 
 
 
 
 
 
Richard D. Granstein, M.D. – PI 
Date 


Protocol #20-07022368 
Version Date 5/10/24 
6 
 
 
 
 
List of Abbreviations 
 
 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
CGRP 
Calcitonin Gene-related Peptide 
CRF 
Case Report Form 
CTSC 
Clinical Translational Science Center 
DLQI 
Dermatology Life Quality Index 
DSMB 
Data Safety Monitoring Board 
DSMP 
Data Safety Monitoring Plan 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HRBFA 
Human Research Billing Analysis Form 
HUD 
Humanitarian Use Device 
ICF 
Informed Consent Form 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug 
IRB 
ODT 
Institutional Review Board 
Orally Disintegrating Tablet 
PASI 
Psoriasis Area and Severity Index 
PHI 
Protected Health Information 
PI 
Principal Investigator 
REDCap 
Research Electronic Data Capture 
SAE 
Serious Adverse Event 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
UIRTSO 
Unanticipated Problem Involving Risks to Subjects or Others 
WCM 
Weill Cornell Medicine 


Protocol #20-07022368 
Version Date 5/10/24 
 
 
1. Protocol Summary 
 
Full Title: 
Short Title: 
Clinical Phase: 
Principal Investigator: 
Study Description: 
 
 
 
 
 
Sample Size: 
Enrollment: 
 
Study Population: 
 
 
 
Enrollment Period: 
Study Design: 
A Pilot Study of Rimegepant in Moderate Plaque-type Psoriasis 
Rimegepant for psoriasis 
2 
 
Richard D. Granstein, MD 
 
This proposal is for a double-blind, placebo-controlled pilot study 
examining the use of an orally administered small molecule 
competitive inhibitor of the calcitonin gene-related peptide (CGRP) 
receptor for the treatment of moderately severe plaque-type 
psoriasis. We hypothesize that interruption of CGRP signaling will 
prove beneficial in psoriasis. 
 
N=15 for each of 2 cohorts. 
 
The study will enroll 30 subjects and we anticipate screening up to 
110 subjects. 
 
Thirty adults with mild to moderate plaque-type psoriasis who are 
otherwise generally healthy. Subjects for the study will be 18 to 75 
years of age. 
 
The enrollment period will be approximately 3 years 1 month. 
 
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. At the subject’s option, 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 willdiscontinue medications after the end of week 
16. Subjects will be evaluated again at weeks 18 and 20. 
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 


8 
Protocol #20-07022368  
Version Date 5/10/24 
 
 
weeks including an EKG. The inclusion and exclusion criteria 
remain the same. 
 
 
Description of Sites: 
This will be a multi-site study taking place at Weill Cornell 
Medicine/New York-Presbyterian Hospital and Sadick Dermatology 
 
Study Duration: 
The projected end-date for completion of this study is 
approximately 47 months from initiation. 
 
Participant Duration: 
Each individual participant will be in the study for approximately 20 
weeks. If participating in optional extension, they will be in the study for an 
additional 12 weeks for a total of up to 32 weeks. 
 
Study Agent/Device Name 
Intervention Description: 
Rimegepant 75 mg (or placebo) taken orally every other day for 
16 weeks. If a subject enters the extension phase, that subject will take 
rimegepant 75 mg every other day for an additional 12 weeks. 
Primary Objective: 
• 
To determine whether rimegepant, an orally available competitive inhibitor of the CGRP 
receptor, results in improvement in psoriasis compared to placebo as assessed by the 
PASI instrument. 
 
Secondary Objectives: 
 
• 
To determine if the degree of improvement in subjects given rimegepant is at least 50% 
compared to the placebo group as assessed by the PASI instrument. 
 
• 
To determine whether rimegepant significantly improves psoriasis compared to placebo 
as assessed by the Investigator’s Global Assessment (IGA) instrument. 
 
• 
To determine whether rimegepant significantly improves quality of life as assessed by 
the Dermatology Quality of Life Index (DQLI) as compared to placebo for subjects with 
psoriasis. 
 
• 
To determine whether rimegepant significantly improves the degree of itching (itch 
score) for patients with psoriasis as compared to placebo. 
 
Primary Endpoints: 
 
1. PASI instrument score 
Assessments will be made at baseline and every 2 weeks for 20 weeks. 
 
Secondary Endpoints: 
 
1. Fifty percent improvement in PASI instrument. 
2. IGA instrument score. 
3. DLQI instrument score. 
4. Itch Score. 


9 
 
 
Protocol 
#20-07022368 Version 
Date 5/10/24 
 
1.1 Schema 
 
 
Prior to 
Enrollment 
 
 
 
 
 
 
 
Visit 1 
Day 0 
 
Visits 2-8 
(2 week intervals) 
Days 14-98 
 
Visit 9 
Day 112 
 
 
 
Visit 10 
Day 126 
 
 
Visit 11* 
Day 140 
 
 
 
 
 
Extension 
Visit 11*/12 
 
 
 
Extension 
Visits 13-15 
15 participants 
15 participants 
Perform PASI, IGA, DLQI, biopsy, and itch assessments. 
Photography of areas of psoriasis. 
Take history of any adverse effects and other relevant history. 
Dispense 30 tablets of rimegepant or placebo tablets. Subjects receiving ODT of 
rimegepant will be given 32 ODTs of rimegepant or 32 placebo ODTs . 
Perform PASI, IGA, DLQI and itch assessments. 
Photography of areas of psoriasis. 
Take history of any adverse effects and other relevant history. 
Discontinue medications as of this day. 
 
Final Assessments 
Perform PASI, IGA, DLQI and itchassessments. 
Photography of areas of psoriasis. 
Take history of any adverse effects andother relevant 
history. 
Obtain history, perform PASI, IGA, DLQI, EKG, itch assessments and photography. 
Dispense medications on Visits 12 and 14. 
Stop medications Visit 15. 
Obtain informed consent. Screen potential participants by inclusion and exclusion criteria; 
obtain history, perform PASI, IGA, DLQI, EKG, itch assessments and photography. 
Perform PASI, IGA, DLQI and itch assessments. 
Photography of areas of psoriasis. 
Take history of any adverse effects and other relevant history. 
Perform PASI, IGA, DLQI and itch assessments. 
Photography of areas of psoriasis. 
Take history of any adverse effects and other relevant history. 
Dispense 30 tablets of rimegepant or placebo tablets (Day 56 only). Subjects receiving ODT of rimegepant will be 
given 32 ODTs of rimegepant or 32 placebo ODTs . 


Protocol #20-07022368 
Version Date 5/10/24 
10 
 
 
 
 
1.2 
Study Objectives and End Points 
 
1.2.1 
Primary Objectives 
 
To determine whether rimegepant, an orally available competitive inhibitor of the CGRP 
receptor, results in improvement in psoriasis compared to placebo as assessed by the 
PASI instrument. 
 
1.2.2 
Secondary Objectives 
 
To determine whether treatment of psoriasis with rimegepant significantly improves patient’s 
quality of life as assessed by the Dermatology Quality of Life Index (DQLI), itch score, and 
IGA instrument, as well as by a 50% improvement according to the PASI instrument. 
 
1.2.3 
Exploratory Objectives 
 
Explore the pattern of PASI score over time during treatment. 
 
Describe changes in circulating CD4+ IL-17+ T cells during treatment with rimegepant or 
placebo. 
 
Describe histologic changes in psoriasis lesions during treatment with rimegepant or 
placebo. 
 
1.2.4 
Primary Endpoints 
 
1. PASI instrument score. 
 
 
Assessments will be made at baseline and every 2 weeks for 20 weeks. 
 
1.2.5 
Secondary Endpoints 
 
1. To determine if the degree of improvement in subjects given rimegepant is at least 50% 
compared to the placebo group as assessed by the PASI instrument. 
 
2. To determine whether rimegepant significantly improves psoriasis compared to placebo 
as assessed by the Investigator’s Global Assessment (IGA) instrument. 
 
3. To determine whether treatment of psoriasis with rimegepant significantly improves 
patient’s quality of life as assessed by the Dermatology Quality of Life Index (DQLI). The 
DQLI instrument will be administered at baseline and every 2 weeks for 20 weeks. 
 
4. To determine whether rimegepant significantly improves the degree of itching (itch score) 
for patients with psoriasis as compared to placebo. 


Protocol #20-07022368 
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11 
 
 
 
 
 
 
2. Background 
 
2.1 Disease 
 
Psoriasis is a common inflammatory skin disorder characterized by erythematous, scaly 
lesions that may occur anywhere but have a predilection for the scalp, extensor surfaces of 
the extremities, especially the elbows and knees, and the anogenital area (1). Psoriasis can 
be considered a systemic inflammatory disorder and part of the metabolic syndrome. It is 
frequently associated with a form of arthritis, known as psoriatic arthritis (2). It is associated, 
especially when severe, with cardiovascular disease, non-alcoholic fatty liver disease, 
inflammatory bowel disease, depression and lymphomas (2). Psoriasis affects 
approximately 2-3% of the population. Mild and limited psoriasis can be treated with a 
variety of topical agents including corticosteroids, calcipotriene, topical retinoids, crisaborole, 
amongst others (3-5). When severe, treatment is primarily with immunosuppressive agents 
including methotrexate, cyclosporine, 6-thioguanine and, more recently, a number of 
biological agents that block tumor necrosis alpha, interleukin-23, interleukin-17, the JAK- 
STAT signaling system, and phosphodiesterase inhibitors, or phototherapy (broad-band or 
narrow-band UVB radiation; psoralen plus UVA radiation), amongst others (3-5). All of 
these systemic medications and phototherapy have undesirable side effects caused by 
immunosuppression, gastrointestinal effects or other unwanted side effects. Thus, a need 
exists for safer effective systemic therapies. 
 
2.2 Investigational Agent/Device, or Surgical Treatment/Method 
 
PK/Clin Pharm 
 
This study is testing the impact of rimegepant in the setting of psoriasis. Rimegepant is a 
small molecule antagonist of the CGRP receptors, thus limiting CGRP signaling. 
Rimegepant is approved for acute migraine. After administration of the 75 mg tablet, time to 
maximum plasma concentration (Tmax) occurs at a median of 1.9 h. The two clinical 
formulations of rimegepant, the tablet and oral disintegrating tablet (ODT), are bioequivalent. 
The absolute oral bioavailability of rimegepant in the fasted state is approximately 64%. The 
effects of a high-fat meal on the tablet formulation showed that overall, a high-fat meal 
decreased the mean AUC and Cmax of rimegepant by 30% and 33% , respectively, and 
delayed the Tmax by approximately one hour. Based on the weight of evidence from three 
positive Phase 3 studies in migraine conducted without food restrictions, rimegepant 75 mg, 
administered as a tablet or ODT, may be administered without regard to food. 
The clinical dose of rimegepant is 75 mg. Rimegepant exposures increased over the single 
dose range of 25 mg to 900 mg. Steady state is achieved by Day 2 following once daily 
dosing with no meaningful accumulation. Rimegepant 75 mg has low to moderate PK 
variability, with coefficient of variation (CV%) characterized as Cmax = 40% and AUC0-inf = 
30% for the tablet. Based on population PK analysis, the elimination half-life in normal 
healthy subjects is 11 hours. 
 
The steady state volume of distribution averages approximately 120.4 L. Rimegepant is 
approximately 96% bound to human plasma proteins. 


Protocol #20-07022368 
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12 
 
 
 
 
The primary route of elimination is through the feces. Rimegepant is the primary circulating 
component in plasma, with 88% to 92% unchanged parent present throughout the first 
4 hours. Over longer periods of time, unchanged rimegepant represents approximately 77% 
of the total administered dose with only low quantifiable levels of circulating metabolites of 
rimegepant. CYP3A4 is the primary metabolizing enzyme. 
 
2.3 Rationale 
 
Considerable evidence in both humans with psoriasis and animal models of psoriatic 
dermatitis indicate that CGRP may play a key role in the pathophysiology of this disease. In 
human psoriasis, denervation, administration of local anesthetics or administration of 
botulinus toxin to the site of skin bearing psoriasis causes improvement or resolution of the 
disease at those sites demonstrating the importance of innervation for expression of the 
disease (6-9). In two mouse models of psoriatic dermatitis, innervation is also necessary for 
expression of the rash (10,11); in one mice are engineered to express the angiopoietin 
receptor Tie-2 (10) and in the other imiquimod is applied to the skin of mice of certain strains 
(11). In each, a psoriasiform dermatitis results. In humans, plasma CGRP is elevated in 
psoriasis patients compared to controls (12), an increased CGRP content of skin is noted in 
psoriatic lesions (13) and CGRP can be detected on the surface of endothelial cells in 
lesional skin (13). In the Tie-2 model of psoriasiform dermatitis, systemic administration of 
CGRP can retard the loss of the rash by denervation of the skin (6). In the imiquimod model 
of psoriasiform dermatitis, nerves release a factor, likely CGRP, that is key for development 
of the rash (14,15). Recent work from our laboratory has shown that CGRP treatment of 
endothelial cells endows them with the capacity, acting as bystanders, to bias the outcome 
of antigen presentation away from the Th1 pole towards Th17-type immunity (16). This may 
be relevant to psoriasis as psoriasis is an IL-17/Th17 cell mediated disorder. For all of these 
reasons, a trial of an agent that interrupts CGRP-signaling in psoriasis is warranted. In this 
regard, rimegepant is approved for use in humans for the treatment of migraine and is safe 
and well-tolerated (17). For all of these reasons, a trial of an agent that interrupts CGRP 
signaling in psoriasis is warranted. 
 
2.4 Risk/Benefit Assessment 
 
2.4.1 
Known Potential Risks 
 
From the package insert of Nurtec (rimegepant): 
 
The most common adverse reaction in Study 1 was nausea (2% in patients who 
received NURTEC ODT compared to 0.4% of patients who received placebo). 
 
Hypersensitivity, including dyspnea and severe rash, occurred in less than 1% of 
patients treated with NURTEC ODT 
 
Hypersensitivity reactions, including dyspnea and rash, have occurred with NURTEC ODT 
in clinical studies. Hypersensitivity reactions can occur days after administration, and 
delayed serious hypersensitivity has occurred. 
 
Concomitant administration of rimegepant with strong inhibitors of CYP3A4 results in a 
significant increase in rimegepant exposure. 


Protocol #20-07022368 
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13 
 
 
Concomitant administration of rimegepant with moderate inhibitors of CYP3A4 may 
result in increased exposure of rimegepant. 
 
Concomitant administration of rimegepant with strong or moderate inducers of CYP3A can 
result in a significant reduction in rimegepant exposure, which may lead to loss of efficacy. 
 
Rimegepant is a substrate of permeability glycoprotein (P-gp) and Breast Cancer 
Resistance Protein (BCRP) efflux transporters. Concomitant administration of rimegepant 
with inhibitors of P-gp or BCRP may result in a significant increase in rimegepant 
exposure. 
 
Potential subjects on any medication that is a strong or moderate inhibitor of 
CYP3A, a strong or moderate inducer of CYP3A or an inhibitor of p-gp or BCRP 
will be excluded from participation in the study. 
 
2.4.2 
Known Potential Benefits 
 
Rimegepant is effective as treatment for migraine. 
 
2.4.3 
Assessment of Potential Risks and Benefits 
 
There is a medical need for effective systemic treatments for psoriasis with better safety 
profiles than currently available agents. Rimegepant has been shown to be safe and 
effective for treatment of migraine events. It has the potential to be a safe and, based on 
preclinical studies, an effective systemic treatment for psoriasis. 
 
 
2.5 Correlative Studies Background 
 
Not applicable. 
 
3. Study Design 
 
3.1 Overall Design 
This is a phase 2, randomized double-blind controlled pilot study to assess whether 
there is clinical improvement in psoriasis after administration of a small molecule CGRP 
receptor inhibitor, rimegepant, compared to placebo. Rimegepant and placebo will be 
identical appearing 75 mg tablets/ODTs administered orally every other day. The study 
will be conducted solely at Weill Cornell Medicine and last 20 total weeks with 16 weeks 
of medication or placebo administration and 4 additional weeks of follow-up. Subjects will 
present to clinic every 2 weeks for clinical assessment using the PASI, IGA, DLQI, and 
Itch Score instruments, along with skin biopsies on Week 1 and Week 16. Subjects will 
be asked to bring their medications to these visits for pill counts to determine if any 
doses of medication were forgotten. 


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Study medications will be dispensed on Day 0 and Day 56. Thirty will be dispensed eachtime 
so that enough medication is provided in case of a minor delay in a scheduled appointment. 
 
Areas of psoriasis in each subject will be photographed at baseline and two very similar 
appearing lesions will be identified for possible biopsy of one on Day 1 and the other at the end 
of Week 16. Prior to starting treatment and at the end of week 16 they will have blood taken for 
quantification of the proportion of circulating CD4+ T cells that are IL-17+ . 
 
At the option of each subject,biopsies of the psoriatic lesions previously identified (one before 
treatment and one on week 16) will be performed for light microscopy analysis. Biopsies are 
performed by cleaning the skin carefully with an antiseptic, then injecting a small amount of 
local anesthetic into the skin. A 3 or 4 mm diameter trephine punch is then used to remove a 
very small piece of skin. The surgicaldefect is then closed with 1 or 2 sutures that are removed 
2 weeks later. 
 
Subjects will return on weeks 18 and 20 for final assessments. Subjects must also agree to 
avoid the sun including but not limited to activities such as sunbathing, swimming or performing 
other activities in sunlight for long periods of time (e.g., > 20 minutes) for the duration of the 
study. Brief exposure during normal activities is permitted. 
 
Subjects who complete the 20-week protocol will have the option of entering a 12 weeks, open label 
extension of the study in which they will take 75 mg of Rimegepant every other day for 12 weeks. If rolling 
into the extension prior to visit 11, they can combine visit 11 and 12. Otherwise, subjects have the option to 
enroll into the extension up to 2 weeks after visit 11. They will have the same assessments as in the 
previous portion of the study every 4 weeks including an EKG. The inclusion and exclusion criteria remain 
the same. 
 
3.2 Justification for Dose 
 
The dose to be employed (rimegepant 75 mg every other day) has been shown to be safe 
and effective for the treatment of acute migraine. Rimegepant 75 mg every other day (up to 
one year) has been studied in the treatment of migraine prevention. 
 
3.3 End of Study Definition 
 
A participant is considered to have completed the study if he or she has completed all 
phases of the study including the last visit or the last scheduled procedure shown in the 
Schedule of Assessments (SoA), Section 6.1. The end of the study is defined as completion 
of the last visit or procedure shown in the SoA in the trial globally. 
 
4. Subject Selection 
 
4.1 Study Population 
 
Subjects with a diagnosis of psoriasis who meet the inclusion and exclusion criteria will be 
eligible for participation in this study. 
 
4.2 Inclusion Criteria 


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1. Male or female patients with at least 3% body surface are involved with psoriasis and a 
PASI score >5. 
2. Between 18 and 75 years of age. 
3. Documentation of a definite diagnosis of psoriasis by a dermatologist or biopsy. 
4. 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. 
 
5. A valid form of contraception must be documented for men and women of child- 
bearing potential. 
a. The two methods for women of childbearing potential should include: 
i. 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 
ii. One additional method. The other method could include hormonal 
contraceptives, or second barrier method as listed above. 
b. The two options for men of childbearing potential should include: 
i. 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. 
 
 
4.3 Exclusion Criteria 
 
1. 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. 
2. Pregnancy or breastfeeding. 
3. Known autoimmune disorders other than psoriasis. 
4. Current use of corticosteroids or immunosuppressive medications (for any reason). 
5. Immunodeficiency diseases. 
6. Use of any biologic agent/monoclonal antibody within 5 half-lifes prior to baseline. 
7. 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. 
8. Participation in another clinical trial involving an investigational drug within the last 30 
days prior to baseline. 
9. Inability for woman of child-bearing potential to use an effective form of contraception if 
sexually active. 
10. 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. 
11. 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. 


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12. 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 
13. 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 theScreening visit. 
14. Subject has a history or diagnosis of Gilbert’s Syndrome or any other active hepatic or 
biliary disorder 
15. 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. 
16. Subject has current diagnosis of major depressive disorder requiring treatment with 
atypical antipsychotics, schizophrenia, bipolar disorder, or borderline personality 
disorder. 
17. History of gallstones without cholecystectomy. 
18. Subject has current diagnosis of major depressive disorder requiring treatment with 
atypical antipsychotics, schizophrenia, bipolar disorder, or borderline personality 
disorder. 
19. Subject has end-stage kidney disease. 
20. 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. 
21. Concomitant use of atypical antipsychotics such as Abilify (aripiprazole), Zyprexa 
(olanzapine), Seroquel (quetiapine), Geodon (ziprasidone), or Risperdal (risperidone). 
22. Depakote/Depakene (divalproex/valproic acid/valproate) is prohibited during the study. 
23. Concomitant use of LAMICTAL (lamotrigine) is prohibited during the study. 
24. Concomitant use of Modafinil (PROVIGIL®) is prohibited during the study. 
25. 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% 
 
 
4.4 Lifestyle Considerations 
 
Not applicable. 
 
4.5 Screen Failures 
 
Individuals who do not meet the criteria for participation in this trial (screen failure) because 
of a use of a disqualifying medication may be rescreened after the required period of not 
using that medication. Rescreened participants will be assigned the same participant 
number as for the initial screening. 


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4.6 Strategies for Recruitment and Retention 
5. Registration Procedures 
5.1 Subject Registration (WCM only) 
 
Subjects will be registered within the WRG-CT as per the standard operating procedure 
for Subject Registration. 
 
5.2 Subject Registration (Sub-sites) 
 
Not applicable. 
 
6. Study Procedures 
 
6.1 Schedule of Assessments 
Visit Number: 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Pre- 
Study 
Day
0 
Wk 
2 
Wk
4 
Wk
6 
Wk 
8 
Wk
10
Wk 
12 
Wk 
14 
Wk 
16 
Wk
18 
Wk
20 
Informed consent 
X 
Evaluation for Entry 
X 
Demographics 
X 
Medication 
History 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medical History* 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
Weight 
X 
Vital Signs 
X 
Skin Exam + Photos* 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PASI Score 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IGA Score 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
DLQI Score 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Itch Score 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy test 
X 
X 
X 
X 
X 
X 
X
X 
X 
X 
X 
X 
CMP, CBC w/Diff, 
X 
X 
T Cell FACS, Biopsy of 
Skin Lesion 
X 
HIV Serology, HbA1c 
X 


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Assess Adverse Event 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECG 
X 
X 
X 
X 
X 
Randomization 
X 
Medication 
Dispensation 
X 
X 
Pill Counts 
X 
X 
X 
X 
X 
X 
X 
X 
All visits have a +/- 2-day window. Each visit is first day of the week indicated. 
 
 
 


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*Subjects enrolling in extension prior to visit 11 can combine visit 11 and 12. 
**Skin Exam: The entire glabrous skin surface will be examined. 
**Photography: Photographs will be taken to demonstrate the extent and morphology of lesions 
of psoriasis. 
**Medical History: Characteristics of the patient’s psoriasis will be obtained (duration, areas of 
involvement, past therapies and degree of itch). History of active medical problems, any 
immunosuppressive disorders will be queried. Family history of psoriasis or other inflammatory 
skin diseases will also be obtained. 
6.1.1 
Screening Visit (2-10 days before start of treatment) 
• 
Informed consent 
• 
Demographics 
• 
Medication history 
• 
Medical history 
• 
Skin exam + photos 
• 
PASI Score 
• 
IGA Score 
• 
DLQI Score 
• 
Itch Score 
• 
Beta-HCG 
• 
HIV Serology 
• 
CBC w/Diff, CMP, Hemoglobin A1c 
• 
ECG 
6.1.2 
Treatment Phase 
Eligible subjects will be randomly assigned to rimegepant or placebo treatment 
groups in a 1:1 ratio using a stratified permuted block randomization scheme 
developed by the data manager/study statistician. 
 
6.1.2.1 Visit 1 (baseline; Day 0) 
 
• 
Medication history (changes) 
• 
Medical history (changes) 
• 
Skin exam + photos 
• 
PASI score 
• 
IGA Score 
• 
DLQI Score 
• 
Itch Score 
• 
Adverse Events Assessment 
• 
Concomitant medication 
 
6.1.2.2 Visits 2-12 (± 2 day(s)) 
 
• 
Medication history (changes) 
• 
Medical history (changes) 
• 
Skin exam + photos 
• 
PASI score 
• 
IGA Score 
• 
DLQI Score 


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• 
Itch Score 
• 
Adverse Events Assessment 
• 
Concomitant medication 
• 
ECGs will be obtained on Visits 3,5,7 and 9. 
 
6.1.3 
Follow-up Phase 
 
Visits 11 and 12 are follow-ups after completion of the treatment phase 
 
Extension Phase 
 
Visits 13-15 have the same assessments as visits 2-12 except they will 
have a frequency of every 4 weeks. 
 
7. Study Intervention 
 
 
7.1 Study Intervention/Device Description 
 
In this protocol, the investigational product will come in 2 forms either tablet or ODTs. 
Both active forms of tablets and ODTs will have 75mg of rimegepant and both 
formulations provide bioequivalent exposures, thus support equivalent PK 
performance. The tablets will be provided in 30 count HDPE bottles and labeled in a 
double-blind fashion that is identical to placebo tablets. The ODTs are packaged into 
multi-laminated blisters sealed with a foil backing and labeled in a double-blind fashion 
that is identical to placebo ODTs. Because the blister packs are in units of 8, 32 ODTs 
of rimegepant or placebo will be distributed. Any leftover investigational product will be 
returned to the study team during visits 5, 9 and if applicable, extension visit 14. 
 
 
The investigational product will be shipped to the pharmacy by Pfizer Inc. and should be 
stored in a secure area according to local regulations. It is the responsibility of the 
investigator to ensure that investigational product is only dispensed to study subjects. 
The investigational product must be dispensed only from official study sites by 
authorized personnel according to local regulations. 
 
7.2 Availability 
 
The full amount of Rimegepant and placebo will be supplied by Pfizer, Inc. and 
shipped to the site pharmacy prior to the initiation of the trial. If additional product is 
required, contact the sponsor directly. 
 
7.3 Acquisition and Accountability 
 
Agent Inventory Records/Device Logs – The investigator, or a responsible party 
designated by the investigator, will maintain a careful record of the inventory and 
disposition of all agents/device received from Sponsor on a Drug Accountability Record 
Form (DARF) or Device Log. 


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7.4 Formulation, Appearance, Packaging, and Labeling 
 
The rimegepant active and placebo tablets are packaged in 30 count HDPE bottles and 
will have a blinded label which will include a unique bottle number, the product name, 
labeling lot number, storage conditions and dosing directions. The unique bottle number 
is linked to the treatment arm in a blinded fashion. The rimegepant active and placebo 
ODTs are packaged in 8-count multi-laminated blisters backed with foil and will be labeled 
similarly to the tablet bottles. 
 
7.5 Product Storage and Stability 
 
The investigational product should be stored at room temperature according to 
conditions on the clinical label in a secure area according to local regulations. 
 
It is the responsibility of the investigator to ensure that investigational product is only 
dispensed to study subjects. The investigational product must be dispensed only from 
official study sites by authorized personnel according to local regulations. 
 
If concerns regarding the quality or appearance of the study drug arise, do not dispense 
the study drug and contact the sponsor immediately. 
 
7.6 Preparation 
 
The investigational product will be assigned by the unblinded pharmacist after patient 
randomization through use of the unique bottle numbers. The pharmacist will add the 
appropriate subject number on the bottle label and provide it to the site staff for 
dispensation to the subject. 
 
7.7 Dosing and Administration 
 
Each subject will take a 75-mg tablet/ODT of rimegepant orally or a matching placebo 
tablet/ODT orally every other day for 16 weeks. Subjects will receive 30 tablets or 32 
ODTs of rimegepant or matching placebo in each bottle or four 8-count blister packs at 
the initial visit after the subject is randomized. The subject will be instructed to dose 
around the same time every other day. The subject must bring the bottle/blister packs 
back for each visit for drug accountability. A second 30 tablet or 32 ODT supply will 
be dispensed at week 8. Pill counts will be performed at each visit to assess 
compliance. 
 
7.7.1 
Dosing Delays/Dose Modifications 
 
For any serious adverse effects, dosing will be immediately discontinued and 
appropriate care provided. Some nausea is expected. 
 
7.8 General Concomitant Medication and Supportive Care Guidelines 
 
Concomitant administration of rimegepant with strong inhibitors of CYP3A4 results in a 
significant increase in rimegepant exposure. 
CYP3A4 Inhibitors (Strong) Interacting Members: Atazanavir, Ceritinib, Clarithromycin, 
Cobicistat, Darunavir, Idelalisib, Indinavir, Itraconazole, Ketoconazole (Systemic), Lopinavir, 
MiFEPRIStone, Nefazodone, Nelfinavir, Ombitasvir, Paritaprevir, 


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and Ritonavir, Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir, Posaconazole, 
Ritonavir, Saquinavir, Telithromycin, Tucatinib, Voriconazole 
Concomitant administration of rimegepant with moderate inhibitors of CYP3A4 may result in 
increased exposure of rimegepant. 
 
 
- 
CYP3A4 Inhibitors (Moderate) Interacting Members: Aprepitant, Conivaptan, 
Crizotinib, DilTIAZem, Dronedarone, Duvelisib, Erythromycin (Systemic), Fedratinib, 
Fluconazole, Fosamprenavir, Fosnetupitant, Grapefruit Juice, Imatinib, 
Isavuconazonium Sulfate, Lefamulin, Letermovir, Netupitant, Nilotinib, Ribociclib, 
Schisandra, Verapamil 
 
Concomitant administration of rimegepant with strong or moderate inducers of CYP3A can 
result in a significant reduction in rimegepant exposure, which may lead to loss of efficacy. 
 
- 
CYP3A4 Inducers (Strong) Interacting Members: Apalutamide, CarBAMazepine, 
Enzalutamide, Fosphenytoin, Lumacaftor and Ivacaftor, Mitotane, PHENobarbital, 
Phenytoin, Primidone, RifAMPin 
- 
CYP3A4 Inducers (Moderate) Interacting Members: Bexarotene (Systemic), 
Bosentan, Cenobamate, Dabrafenib, Efavirenz, Eslicarbazepine, Etravirine, 
Lorlatinib, Modafinil, Nafcillin, Pexidartinib, Rifabutin, Rifapentine, St John's Wort 
 
Rimegepant is a substrate of permeability glycoprotein (P-gp) and Breast Cancer 
Resistance Protein (BCRP) efflux transporters. Concomitant administration of rimegepant 
with inhibitors of P-gp or BCRP may result in a significant increase in rimegepant exposure. 
 
- 
BCRP/ABCG2 Inhibitors Interacting Members: Atazanavir, Capmatinib, 
Clopidogrel, Cobicistat, CycloSPORINE (Systemic), Daclatasvir, Darolutamide, 
Dasabuvir, Elbasvir, Eltrombopag, Eluxadoline, Fostamatinib, Fostemsavir, 
Glecaprevir and Pibrentasvir, Grazoprevir, Lapatinib, Ledipasvir, Leflunomide, 
Lopinavir, Ombitasvir, Paritaprevir, and Ritonavir, Ombitasvir, Paritaprevir, Ritonavir, 
and Dasabuvir, Osimertinib, Regorafenib, Rolapitant, Simeprevir, Tedizolid, 
Teriflunomide, Velpatasvir, Voxilaprevir 
- 
P-glycoprotein/ABCB1 Inhibitors Interacting Members: Amiodarone, 
Azithromycin (Systemic), Capmatinib, Carvedilol, CycloSPORINE (Systemic), 
Daclatasvir, Dronedarone, Elagolix, Elagolix, Estradiol, and Norethindrone, 
Elexacaftor, Tezacaftor, and Ivacaftor, Eliglustat, Erythromycin (Systemic), 
Flibanserin, Fostamatinib, Glecaprevir and Pibrentasvir, Ivacaftor, Lapatinib, 
Ledipasvir, Neratinib, Osimertinib, Propafenone, QuiNIDine, QuiNINE, Ranolazine, 
Rolapitant, Simeprevir, Tezacaftor and Ivacaftor, Tucatinib, Velpatasvir, 
Vemurafenib, Verapamil 
Exceptions Clarithromycin, Itraconazole, Ketoconazole (Systemic), Ombitasvir, 
Paritaprevir, and Ritonavir, Ritonavir 
 
Potential subjects on any medication that is a strong or moderate inhibitor of CYP3A, 
a strong or moderate inducer of CYP3A or an inhibitor of p-gp or BCRP will be 
excluded from participation in the study. 


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All concomitant medications will be recorded and/or updated on subject medication log 
throughout the course of the study and saved in subject binder, if applicable. 
 
7.9 Duration of Therapy and Criteria for Removal from Study 
 
 
In the absence of treatment delays due to adverse event(s), treatment will continue for 
16 weeks or until one of the following criteria applies: 
 
• 
Disease progression requiring intervention, 
• 
Intercurrent illness that prevents further administration of treatment, 
• 
Unacceptable adverse event(s), 
• 
Subject decides to withdraw from the study, 
• 
Initiation of prohibited medication, or 
• 
General or specific changes in the subject’s condition render the subject 
unacceptable for further treatment in the judgment of the investigator. 
 
7.10 Duration of Follow Up 
 
Subjects will be followed for 4 weeks after discontinuation of the investigative 
pharmaceutical agent. Subjects removed from study for unacceptable adverse events 
will be followed until resolution or stabilization of the adverse event. 
 
7.11 Measures to Minimize Bias: Randomization and Blinding 
 
Screening and Registration into the Study Database 
Once informed consent has been signed, participants will be registered into the study 
database. The study database will assign a participant’s PID upon completion of the 
registration process. 
 
Randomization: 
Participants will be assigned a randomization number once the following has been 
accomplished: eligibility has been verified, eligibility has been confirmed by the study PI, 
and eligibility CRF has been entered into the study database. 
 
Patients will be stratified based on severity of disease as measured by PASI scores<12 
(mild/moderate) or >=12 (Severe) at screening. Within each stratum, patients will be 
randomized at 1: 1 ratio to the two treatment arms using permuted block randomization 
with varying block sizes. Randomization codes will be shared to the study pharmacist at 
the initiation of the trial. The randomization will be performed by the statistician who will 
alert the pharmacy in coordination with the study coordinator. 
 
Screening/Registration/Randomization into Study Databases 
Appropriate CRFs must be completed for any participant who signs an informed 
consent. If a consented participant is a screen failure and deemed ineligible, the 
following CRFs must be completed: 1) the Screening CRF; 2) the Registration CRF with 
the eligibility box checked “no”, 3) the Inclusion and Exclusion CRFs showing why the 
participant is ineligible, 4) the Off-Study CRF, 5) the Adverse Event CRF, 6) the 
Concomitant Medication CRF and 7) the Verification CRF. If no Adverse Event and/or 
Concomitant Medications were assessed by the time the participant is deemed ineligible, 
the “NONE” box will be checked to complete both CRFs. All participants who sign an 
informed consent must formally go off study. All participant registration information will 


Protocol #20-07022368 
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be entered into study database. If a participant experiences a serious adverse event 
during the screening process, an SAE form must be completed. 
 
Blinding and Unblinding Method 
 
- 
Patients and all clinical evaluators will be blinded to treatment assignment. 
- 
The Statistician and the Study Pharmacist at the participating sites will not be blinded 
to treatment assignment. 
- 
Study assignments will be unblinded to the Study Investigators and Coordinators 
after all of the data are collected, the study database has been locked, and analyses 
are completed. 
- 
Emergency unblinding will occur if the participant’s physician deems that unblinding 
is necessary, such as in the case of unacceptable toxicity thought to be related to the 
study agent or progressive disease. 
- 
The Independent Medical Monitor will also be blinded unless unblinding is warranted 
(if the participant’s physician deems that unblinding is necessary, or after all of the 
data are collected and the study database has been locked). 
- 
The date and reason for breaking the blind must be documented in the study 
database. 
7.12 Study Intervention/Follow-up Compliance 
 
Subject will be asked to complete a log documenting the date and time that the study 
medication is taken (every other day). 
 
Pill counts will be done at each visit. 
 
If necessary, 3 attempts will be made to get subject to return for study follow-up 
Appointments. If the patient does not respond to 3 attempts he/she will be considered 
“lost to follow-up” and no longer participating in the study. 
 
8. Study Intervention Discontinuation and Participant Discontinuation/Withdrawal 
 
8.1 Discontinuation of Study Intervention 
 
Subjects will be withdrawn from study treatment permanently for the following reasons: 
 
1. Development of any hypersensitivity phenomena that may be related to the study 
medication. 
2. Excessive nausea making continuation of participation in the study impossible. 
3. Development of any intercurrent illness or medical need to take a medication such 
that exclusion criteria apply. 
4. Occurrence of pregnancy in a female subject. 
5. If any clinical adverse event (AE), laboratory abnormality, or other medical condition 
or situation occurs such that continued participation in the study would not be in the best 
interest of the participant 
6. Disease progression which requires discontinuation of the study intervention 
7. If the participant meets an exclusion criterion (either newly developed or not 
previously recognized) that precludes further study participation 


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Subjects will be referred for appropriate medical care for any adverse effects. 
 
Subjects will continue to be followed for assessment of disease severity until the 20- 
week period is over. 
 
Discontinuation of treatment does not mean discontinuation from the study, and 
remaining study procedures (assessments of disease severity) will be completed as 
indicated by the study protocol. 
 
If a clinically significant finding is identified (including, but not limited to changes from 
baseline) after enrollment, the investigator or qualified designee will determine if any 
change in participant management is needed. Any new clinically relevant finding will be 
reported as an adverse event (AE). 
 
Criteria for interrupting the study: We will have a study monitoring committee (SMC) 
consisting of the study PI, the medical monitor and 1 investigator not directly involved in 
the conduct of this study. This committee will review all Grade 3 or 4 events, and all 
SAEs in real time. We will pause enrollment of new participants if there is 1 or more 
Serious Adverse Events that are at least possibly related to study drug, or 2 or more 
Grade 3 or 4 events at least possibly related to study drug. The enrollment of 
participants will not resume until the SMC reviews the adverse events and agrees 
unanimously to resume enrollment. 
 
8.2 Participant Discontinuation/Withdrawal from the Study 
 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue or withdraw a participant from the study for the following 
reasons: 
1. Pregnancy. However, subjects will be followed until the end of the pregnancy. 
2. Significant study intervention non-compliance (failure to take medications, refuses to 
allow study procedures). 
3. Participant lost to follow-up after 3 attempts to contact subject to schedule study visit. 
 
The reason for participant discontinuation or withdrawal from the study will be recorded 
on the Case Report Form (CRF). Subjects who sign the informed consent form and are 
randomized but do not receive the study intervention may be replaced. Subjects who 
sign the informed consent form, and are randomized and receive the study intervention, 
and subsequently withdraw, or are withdrawn or discontinued from the study will not be 
replaced. 
 
8.3 Lost to Follow Up 
 
A participant will be considered lost to follow-up if he or she fails to return for a 
scheduled visit and is unable to be contacted by the study site staff. 
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
 
• 
The site will attempt to contact the participant and reschedule the missed visit within 
2 days and counsel the participant on the importance of maintaining the assigned 
visit schedule and ascertain if the participant wishes to and/or should continue in the 
study. 


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• 
Before a participant is deemed lost to follow-up, the investigator or designee will 
make every effort to regain contact with the participant (where possible, 3 
telephone calls). These contact attempts should be documented in the 
participant’s medical record or study file. 
• 
Should the participant continue to be unreachable, he or she will be considered to 
have withdrawn from the study with a primary reason of lost to follow-up. 
 
9. Correlative/Special Studies 
Not applicable. 
10. 
Measurement of Effect 
10.1 Response Criteria 
Not applicable. 
10.2 Duration of Response 
Not applicable. 
10.3 Progression-Free Survival 
Not Applicable. 
10.4 Other Response 
Parameters 
Not Applicable. 
 
11. Data Reporting / Regulatory Considerations 
 
11.1 Data Collection 
The data collection plan for this study is to utilize REDCap to capture all treatment, 
toxicity, efficacy, and adverse event data for all enrolled subjects. 
 
11.1.1 REDCap 
REDCap (Research Electronic Data Capture) is a free data management software 
system that is fully supported by the Weill-Cornell Medical Center CTSC. It is a tool for 
the creation of customized, secure data management systems that include Web-based 
data-entry forms, reporting tools, and a full array of security features including user and 
group based privileges, authentication using institution LDAP system, with a full audit 
trail of data manipulation and export procedures. REDCap is maintained on CTSC- 
owned servers that are backed up nightly and support encrypted (SSL-based) 
connections. Nationally, the software is developed, enhanced and supported through a 
multi-institutional consortium led by the Vanderbilt University CTSA. 
 
11.2 Regulatory Considerations 
11.2.1 Institutional Review Board/Ethics Committee Approval 
 
As required by local regulations, the Investigator will ensure all legal aspects are covered, 
and approval of the appropriate regulatory bodies obtained, before study initiation. 


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Before initiation of the study at each study center, the protocol, the ICF, other written 
material given to the patients, and any other relevant study documentation will be 
submitted to the appropriate Ethics Committee. Written approval of the study and all 
relevant study information must be obtained before the study center can be initiated or the 
IP is released to the Investigator. Any necessary extensions or renewals of IRB approval 
must be obtained for changes to the study, such as amendments to the protocol, the 
ICF, or other study documentation. The written approval of the IRB together with the 
approved ICF must be filed in the study files. 
The Investigator will report promptly to the IRB any new information that may adversely 
affect the safety of the patients or the conduct of the study. The Investigator will submit written 
summaries of the study status to the IRB as required. On completion of the study, the IRB 
will be notified that the study has ended. 
 
All agreed protocol amendments will be clearly recorded on a protocol amendment form 
and will be signed and dated by the original protocol approving signatories. All protocol 
amendments will be submitted to the relevant institutional IRB for approval before 
implementation, as required by local regulations. The only exception will be when the 
amendment is necessary to eliminate an immediate hazard to the trial participants. In this 
case, the necessary action will be taken first, with the relevant protocolamendment following 
shortly thereafter. 
Once protocol amendments or consent form modifications are implemented at the lead 
site, Weill Cornell Medicine, updated documents will be provided to participating sites, as 
applicable. Weill Cornell Medicine must approve all consent form changes prior to local 
IRB submission. 
An IND, including relevant study documentation, will be submitted to the FDA, according 
to national requirements, for review and approval before the beginning of the study. On 
completion of the study, the FDA will be notified that the study has ended. 
 
11.2.2 Ethical Conduct of the Study 
 
The Investigators and all parties involved should conduct this study in adherence to the ethical 
principles based on the Declaration of Helsinki, GCP, ICH guidelines and the applicable national 
and local laws and regulatory requirements. 
 
This study will be conducted under a protocol reviewed and approved by the applicable ethics 
committees and investigations will be undertaken by scientifically and medically qualified 
persons, where the benefits of the study are in proportion to the risks. 
 
11.2.3 Informed Consent 
 
The investigator or qualified designee must obtain documented consent according to ICH- GCP 
and local regulations, as applicable, from each potential subject or each subject’s legally 
authorized representative prior to participating in the research study. Subjects who agree to 
participate will sign the approved informed consent form and will be provided a copy of the 
signed document. 
 
The initial ICF, any subsequent revised written ICF and any written information provided to the 
subject must approved by IRB prior to use. The ICF will adhere to IRB requirements, applicable 
laws and regulations. 


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11.2.4 Compliance with Trial Registration and Results Posting Requirements 
 
Under the terms of the Food and Drug Administration Modernization Act (FDAMA) and the 
Food and Drug Administration Amendments Act (FDAAA), the Sponsor-Investigator of the trial 
is solely responsible for determining whether the trial and its results are subject to the 
requirements for submission to http://www.clinicaltrials.gov. Information posted will allow 
subjects to identify potentially appropriate trials for their disease conditions and pursue 
participation by calling a central contact number for further information on appropriate trial 
locations and trial site contact information. 
 
11.2.5 Record Retention 
 
Essential documents are those documents that individually and collectively permit 
evaluation of the study and quality of the data produced. After completion of the study, all 
documents and data relating to the study will be kept in an orderly manner by the Investigator 
in a secure study file. Essential documents should be retained for 2 years after the final 
marketing approval in an ICH region or for at least 2 years since the discontinuation of clinical 
development of the IP. In addition, all subjects medical records and other source 
documentation will be kept for the maximum time permitted by the hospital, institution, or 
medical practice. 
 
12. Statistical Considerations 
 
12.1 Study Design/Endpoints 
 
This is a randomized, double-blind, placebo-controlled phase II study to examine the 
efficacy of rimegepant, an orally available competitive inhibitor of the CGRP receptor, in 
patients diagnosed with psoriasis. Patients in each strata of disease severity as defined by 
baseline PASI score (<12, or >=12) will be randomized at 1:1 ratio to receive 16-week 
treatment of either rimegepant or placebo. The primary endpoint includes the percent 
reduction in PASI score post-treatment measured at week 16 from baseline defined as 
100% x (PASI.pre-PASI.post)/PASI.pre. Secondary endpoints include PASI50, an indicator 
of whether a patient had at least 50% improvement in PASI score at week 16 post-treatment 
compared to baseline, the reduction (i.e., the difference) in the Investigator’s Global 
Assessment (IGA) score post treatment from baseline, change in Dermatology Quality of 
Life Index (DQLI) at week 16 post treatment compared to baseline, change in Itch Score 
post treatment from baseline, and the overall patterns of change in PASI scores, IGA scores 
and DQLI scores measured longitudinally. 
 
12.2 Sample Size/Accrual Rate 
 
The primary objective of the study is to examine if patients receive the rimegepant treatment 
had greater improvement in psoriasis in terms of the primary endpoints compared to patients 
received the placebo. The primary endpoints include both the percent reduction in PASI 
score post-treatment from baseline and the change IGA score post-treatment from baseline. 
 
The sample size is determined to ensure adequate power to detect clinically meaningful 
differences in the co-primary endpoints between the treatment arms. With a sample size of 
30 patients (15 per treatment arm), we will have 80% power to detect an effect size as small 


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as 1.06 using a two-sample t-test at a two-sided significance level of 0.05 for each of the 
primary endpoint. This level of effect size corresponds to >21% differences in the percent 
reduction in PASI scores post treatment from baseline between the two treatment arms 
assuming the standard deviation of the percent reduction in PASI score is about 20% which 
is likely to be a conservative estimate based on published results from trials in patients with 
moderate to severe disease. This level of effect size also corresponds to a difference of 0.5 
in the change of IGA scores between the two study arms assuming the standard deviation of 
change is around 0.5. Accounting for a dropout rate of 25% a total of 45 patients will be 
recruited. 
 
The study expects to accrue 5 patients per month and accrue all study patients within 6-10 
months. 
 
12.3 Stratification Factors 
 
Patients will be stratified based on severity of disease as measured by PASI scores<12 or 
>=12 at screening. Within each stratum, patients will be randomized at 1: 1 ratio to the two 
treatment arms using permuted block randomization with varying block size. 
 
12.4 Analysis of Endpoints 
 
12.4.1 Analysis of Primary Endpoints 
 
The primary endpoint is the week 16 PASI score. We will calculate the percent reduction in 
week 16 PASI scores post treatment from baseline. Summary statistics in terms mean, 
standard deviation, median and range or inter-quartile range will be generated for each study 
arm. Between treatment arm differences will be evaluated using a two-sample t-test or the non- 
parametric Wilcoxon rank sum test where appropriate. The primary analysis will be carried 
out on an intention-to-treat basis. Last value carried forward will be used to impute for patients 
missing week 16 measurements. Per-protocol analysis will also be carried out amongpatients 
who are deemed compliant to treatment (defined as at least 75% of doses taken asmeasure by 
pill counts) and had both baseline and week 16 measurements will also be carried out using 
similar statistical methods. P-values less than 0.05 will be considered statistical significant. 
 
12.4.2 Analysis of Secondary Endpoints 
 
Quantification of subjects in each arm achieving PASI50 at week 16, defined as achieving 
>=50% reduction in PASI scores measured at week 16 post treatment from baseline, will be 
summarized. Summary statistics including count and proportion in each treatment arm will be 
provided for patients enrolled in each arm. Differences in proportions between treatment arms 
will be summarized along with 95% confidence interval. Exploratory comparison will be 
carried out using Fisher’s exact test. 
 
For change in IGA scores at week 16 post treatment from baseline, summary statistics in 
terms mean, standard deviation, median and range or inter-quartile range will be generated for 
each study arm. Between treatment arm differences will be evaluated using a two-sample t- 
test or the non-parametric Wilcoxon rank sum test where appropriate. 
 
For change in DQLI scores at week 16 post treatment from baseline, summary statistics in 
terms mean, standard deviation, median and range or inter-quartile range will be generated 


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for each study arm. Between treatment arm differences will be evaluated using a two-sample 
t-test or the non-parametric Wilcoxon rank sum test where appropriate. 
 
For change in Itch Scores at week 16 post treatment from baseline, summary statistics in 
terms mean, standard deviation, median and range or inter-quartile range will be generated 
for each study arm. Between treatment arm differences will be evaluated using a two-sample t- 
test or the non-parametric Wilcoxon rank sum test where appropriate. 
 
For longitudinal measurements of the study endpoints obtained overtime, patterns of 
differences between treatment arms will be evaluated using linear mixed-effects or 
generalized linear-mixed effects models. 
 
For all these study endpoints, the primary analysis will be carried out on an intention-to-treat 
basis. For endpoints concerning change at week 16 from baseline, a conservative method for 
imputation such as last-value carried forward will be used for those missing measurements at 
week 16. For analysis concerning longitudinal data, no missing imputation will be applied. 
Secondary per protocol analyses will also be carried out among patients who complied to 
study treatments. 
 
12.5 Interim Analysis 
 
Not applicable. 
 
12.6 Reporting and Exclusions 
 
12.6.1 Evaluation of Toxicity 
 
All subjects will be evaluable for toxicity from the time of their first treatment with the 
Investigational Agent. Consultation with the Biostatistics Office will allow for completion 
of this section. 
 
12.6.2 Evaluation of Response 
 
All subjects included in the study will be assessed for response to treatment if they have 
received at least 4 weeks of treatments. 
 
13. Adverse Event Reporting Requirements 
 
Adverse event (AE) monitoring and reporting is a routine part of every clinical trial. The 
investigator will be required to provide appropriate information concerning any findings that 
suggest significant hazards, contraindications, side effects, or precautions pertinent to the safe 
use of the drug or device under investigation. Safety will be monitored by evaluation of adverse 
events reported by subjects or observed by investigators or research staff, as well as by other 
investigations such as clinical laboratory tests, x-rays, electrocardiographs, etc. 
 
13.1 Adverse Event Definition 
 
An adverse event (also referred to as an adverse experience) can be any unfavorable 
and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a drug, and does not imply any judgment about 
causality. An adverse event can arise with any use of the drug (e.g., off-label use, use in 


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combination with another drug) and with any route of administration, formulation, or dose, 
including an overdose. 
 
13.1.1 Investigational Agent or Device Risks (Expected Adverse Events) 
 
 
1. Nausea. 
 
2. Rare chance of hypersensitivity reaction. 
 
Any adverse events will be treated appropriately in consultation with the subject’s 
physician or other appropriate physicians. 
 
13.1.2 Adverse Event Characteristics and Related Attributions 
 
CTCAE term (AE description) and grade: The descriptions and grading scales found 
in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 
5.0 will be utilized for AE reporting. A copy of the CTCAE version 5.0 can be 
downloaded from the CTEP web site (http://ctep.cancer.gov). 
 
• 
Attribution of the AE: 
- Definite – The AE is clearly related to the study treatment. 
- Probable – The AE is likely related to the study treatment. 
- Possible – The AE may be related to the study treatment. 
- Unlikely – The AE is doubtfully related to the study treatment. 
- Unrelated – The AE is clearly NOT related to the study treatment. 
 
13.1.3 Recording of Adverse Events 
 
All adverse events will be recorded on a subject specific AE log. The AE log will be 
maintained by the research staff and kept in the subject’s research chart. 
 
13.1.4 Reporting of AE to WCM IRB 
 
All AEs occurring on this study will be reported to the IRB according to the IRB policy, 
which can be accessed via the following link: 
http://researchintegrity.weill.cornell.edu/forms_and_policies/forms/Immediate_Reporting 
_Policy.pdf. 
 
13.1.5 Reporting Events to Participants 
 
Any adverse events or serious adverse events will be reported to all subjects orally and 
in writing promptly. 
 
13.1.6 Events of Special Interest 
 
Not applicable. 
 
13.1.7 Reporting of Pregnancy 
 
If any pregnancies arise during the course of the study, incidence of pregnancy should be 
reported to the IRB according to the IRB policy of Weill Cornell Medicine. 
 
76 


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Pregnancy testing will be conducted at each study visit. If, following the baseline visit, it is subsequently 
discovered that a study subject is pregnant, the subject will be discontinued from the study and 
study medication will be stopped. 
 
The Investigator and/or Co-Investigator will immediately inform the Independent Medical Monitor 
of the event and report the event in accordance with the SAE reporting procedures as described 
in Section 13.2.1 – 13.2.3 
 
 
13.2 Definition of SAE 
 
SAEs include death, life threatening adverse experiences, hospitalization or 
prolongation of hospitalization, disability or incapacitation, overdose, congenital 
anomalies and any other serious events that may jeopardize the subject or require 
medical or surgical intervention to prevent one of the outcomes listed in this 
definition. 
 
13.2.1 Reporting of SAE to IRB 
 
All SAEs occurring on this study will be reported to the IRB according to the IRB policy, 
which can be accessed via the following link: 
https://research.weill.cornell.edu/sites/default/files/immediate_reporting_policy.pdf 
 
 
13.2.2 Reporting of SAE to FDA [For Protocols Where WCMC is the Sponsor- 
Investigator] 
 
IND application sponsor must report any suspected adverse reaction or adverse 
reaction to study treatment that is both serious and unexpected. Unexpected fatal 
or life-threatening suspected adverse reactions represent especially important 
safety information and must be reported to FDA as soon as possible but no later 
than 7 calendar days following the sponsor’s initial receipt of the information. 
i. death, 
ii. a life-threatening adverse event, 
iii. in-patient hospitalization or prolongation of existing hospitalization, 
iv. a persistent or significant incapacity or substantial disruption of the ability 
to conduct normal life functions, or 
v. a congenital anomaly or birth defect 
 
Important medical events that may not result in death, be life-threatening, or 
require hospitalization may be considered serious when, based upon appropriate 
medical judgment, they may jeopardize the patient or research subject and may 
require medical or surgical intervention to prevent one of the outcomes listed as 
serious 


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Select appropriate reporting branch below 
 
CDER INDs: 
 
Food and Drug Administration 
Center for Drug Evaluation and Research 
Division of Dermatology and Dentistry 
5901-B Ammendale Road 
Beltsville, MD 20705-1266 
 
CDER-only Biologic INDs: 
 
Food and Drug Administration 
Center for Drug Evaluation and Research 
Therapeutic Biologic Products Document Room 
5901-B Ammendale Road 
Beltsville, MD 20705-1266 
 
CBER INDs: 
 
Office of xxxx 
Center for Biologics Evaluation and Research 
Food and Drug Administration 
Suite 200N 1401 Rockville Pike 
Rockville, MD 20852-1448 
 
 
13.2.3 Reporting of SAE to Pfizer, Inc 
 
 
Institution will send Pfizer, Inc copies of any and all serious adverse event reports 
filed with the FDA or other applicable regulatory authorities, as well as copies of 
any correspondence with the FDA or other applicable regulatory authorities, 
regarding any and all serious adverse events, irrespective of association or 
relatedness with the Study Drug(s) in the course of the Clinical Trial, , at minimum 
once per year. The Pfizer US drug safety department may request data more 
frequently from the Investigator to support safety reporting. Serious adverse 
event reports are faxed to 1-866-997-8322. Contact information for the Pfizer US 
drug safety team is subject to change. For safety reporting questions, please 
contact Pfizer US safety mailbox contact at SAEFaxmailbox@Pfizer.com. 
 
All SAEs that occur will be promptly reported to the IRB and medical monitor for 
the study. SAEs will be reported in accordance with FDA form MedWatch 
3500A associated with the study investigator’s IND. These IND submissions are 
Expedited Safety Reports (7-day or 15-day reports) as defined by the Code of 
Federal Regulations 21 CFR 312.32(c). An Expedited Safety Report is required 


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34 
 
 
for serious adverse events that are deemed both unexpected and related to the 
investigative drug. The protocol may define that this attribution can include events 
considered “possibly related”, and the IND Sponsor-investigator should align with 
their study protocol in this regard. Serious adverse events that do not fit these 
criteria should still be described in the IND’s Annual Report. All MedWatch 3500A 
forms should be submitted to Biohaven as defined above. These documents are 
critical to updating the comprehensive safety information in our Investigator 
Brochure, which is reviewed and updated at least annually. 
 
 
13.3 AE/SAE Follow Up 
 
All SAEs and AEs reported during this study will be followed until resolution or until the 
investigator confirms that the AE/SAE has stabilized and no more follow-up is required. 
 
13.4 Time Period and Frequency for Event Assessment and Follow Up 
 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to 
the attention of study personnel during study visits and interviews of a study participant 
presenting for medical care, or upon review by a study monitor. 
 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be 
captured on the appropriate case report form (CRF). Information to be collected includes 
event description, time of onset, clinician’s assessment of severity, relationship to study 
product (assessed only by those with the training and authority to make a diagnosis), 
and time of resolution/stabilization of the event. All AEs occurring while on study must be 
documented appropriately regardless of relationship. All AEs will be followed to 
adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. However, if the study participant’s 
condition deteriorates at any time during the study, it will be recorded as an AE. 
 
Changes in the severity of an AE will be documented to allow an assessment of the 
duration of the event at each level of severity to be performed. AEs characterized as 
intermittent require documentation of onset and duration of each episode. 
 
Dr. Granstein or other study key persons will record all reportable events with start dates 
occurring any time after informed consent is obtained until 7 (for non-serious AEs) or 30 
days (for SAEs) after the last day of study participation. At each study visit, the 
investigator will inquire about the occurrence of AE/SAEs since the last visit. Events will 
be followed for outcome information until resolution or stabilization.] 
 
14. Unanticipated Problems Involving 
Risks to Subjects or Others 
 
14.1 Definition of Unanticipated Problems Involving Risks to Subjects 
or Others (UPIRTSO) 


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The Office for Human Research Protections (OHRP) considers unanticipated problems 
involving risks to participants or others to include, in general, any incident, experience, or 
outcome that meets all of the following criteria: 
 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the Institutional Review 
Board (IRB)-approved research protocol and informed consent document; and (b) the 
characteristics of the participant population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there 
is a reasonable possibility that the incident, experience, or outcome may have been 
caused by the procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously known 
or recognized. 
 
14.1.2 Unanticipated Problem Reporting 
 
The investigator will report unanticipated problems (UPIRTSOs) to the reviewing 
Institutional Review Board (IRB) and to the lead principal investigator (PI). The 
UPIRTSO report will include the following information: 
 
• 
Protocol identifying information: protocol title and number, PI’s name, and the 
IRB project number; 
• 
A detailed description of the event, incident, experience, or outcome; 
• 
An explanation of the basis for determining that the event, incident, experience, 
or outcome represents an UPIRTSO; 
• 
A description of any changes to the protocol or other corrective actions that have 
been taken or are proposed in response to the UPIRTSO. 
 
To satisfy the requirement for prompt reporting, UPIRTSOs will be reported using the 
following timeline: 
 
• 
UPIRTSOs that are serious adverse events (SAEs) will be reported to the IRB 
and to the DCC/study sponsor within 24 hours of the investigator becoming 
aware of the event. 
• 
Any other UPIRTSO will be reported to the IRB and to the DCC/study sponsor 
within 7 days of the investigator becoming aware of the problem. 
• 
All UPs should be reported to appropriate institutional officials (as required by an 
institution’s written reporting procedures), the supporting agency head (or 
designee), Food and Drug Administration (FDA), and the Office for Human 
Research Protections (OHRP) within <insert timeline in accordance with policy> 
of the IRB’s receipt of the report of the problem from the investigator.] ????? 
 
15. Data and Safety Monitoring Plan (DSMP) 
 
After discussion with representatives of the Weill Cornell Data and Safety Monitoring Board, at 
their recommendation we have decided to proceed with an Independent Medical Monitor. For a 
study of the relatively short duration of subject participation as in our proposal and the known 
safety of the drug being investigated, this appeared to be the best choice.


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36 
 
 
 
Events that will be captured and submitted to the Monitor are: 
1. Accidental injuries 
2. Events related to trial procedures 
3. Reasons for any unfavorable and unplanned change in medication. 
4. Clinically significant worsening of pre-existing conditions. 
5. Reasons for admission to hospital or surgical procedures unless these admissions or 
procedures were planned before the subject consented to trial participation. 
6. Adverse events anticipated based on the pharmacological effects of rimegepant. 
7. Any laboratory abnormality felt to be clinically significant by the investigator. 
Serious adverse events are defined as: 
1. An event resulting in death 
2. An event that is life-threatening 
3. An event that requires inpatient hospitalization other than planned hospitalizations that 
do not fulfill the criteria for being a serious adverse event. 
4. An event that results in persistent or significant disability or incapacity. 
5. A medically important event that may not be immediately life-threatening or result in 
death or hospitalization but may jeopardize the subject or require intervention to prevent 
one of the outcomes listed above. 
The following adverse events will result in terminating protocol treatment: 
1. Anaphylactic reaction or other systemic reaction to rimegepant. 
2. Any adverse reaction that in the opinion of the investigator contraindicates further 
dosing. 
3. Diagnosis of a malignancy during the trial excluding carcinoma in situ of the cervix or 
localized squamous or basal cell carcinoma of the skin. 
4. Evidence of pregnancy. 
5. Any infection that is opportunistic whose nature or course may suggest an 
immunocompromised status. 
6. Significant abnormalities including an ALT or AST value more than 3 times the upper limit 
of normal, total bilirubin more than 2 times the upper limit of normal unless related to 
Gilbert Syndrome. 
Adverse events that are not accurately reflected in the Informed Consent Form or the package 
insert of the medication that is related or possibly related to the pharmacological intervention 
and that has greater risk of harm to the subject is present than was previously known or 
recognized will be reported to the Independent Medical Monitor within 7 days. Severe adverse 
events will be reported to the Medical Monitor as soon as possible and definitely within 3 days. 
Additionally, quarterly reports on all subjects experiencing adverse events will be submitted to 
the monitor throughout the study. 
 
There are no defined rules for stopping the study prior to completion by all of the enrolled 
subjects. Given the known safety data of the investigational agent. This seems quite 
reasonable. 
The Independent Medical Monitor’s comments will be provided to the IRB at the time of each 
continuing review. 


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J Family Med Prim Care. 2020, 9:20-24. 
 
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Gottlieb AB. Psoriasis. Nat Rev Dis Primers. 2016, 24;2:16082. 
 
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5. Rácz E, Prens EP. Phototherapy of Psoriasis, a Chronic Inflammatory Skin Disease. 
Adv Exp Med Biol. 2017, 996:287-294. 
 
6. Farber EM, Lanigan SW, Boer J. The role of cutaneous sensory nerves in the maintenance of 
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7. Zhu TH, Nakamura M, Farahnik B, Abrouk M, Lee K, Singh R, Gevorgyan A, Koo J, Bhutani 
T. The role of the nervous system in the pathophysiology of psoriasis: A review of cases of 
psoriasis remission or improvement following denervation injury. Am J Clin Dermatol. 2016, 
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8. HH Perlman. Remission of psoriasis vulgaris from the use of nerve-blocking agents. Arch 
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9. Aschenbeck KA, Hordinsky MK, Kennedy WR, Wendelschafer-Crabb G, Ericson ME, Kavand 
S, Bertin A, Dykstra DD, Panoutsopoulou IG. Neuromodulatory treatment of recalcitrant plaque 
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10. Ostrowski SM, Belkadi A, Loyd CM, Diaconu D, Ward NL. Cutaneous denervation of 
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11. EM Baerveldt, AJ Onderdijk, C Wohn, M Kant, EF Florencia, IJ Hekking-Weijma, ET Walbeehm, 
WR Swindell, JE Gudjonsson, EP Prens. Denervation impairs clinical development of 
imiquimodinduced psoriasiform skin inflammation in mice. J Invest Dermatol. 2012,132(Suppl 2s), 
S17 (abstract). 
 
12. Reich A, Orda A, Wiśnicka B, Szepietowski JC. Plasma concentration of selected 
neuropeptides in patients suffering from psoriasis. Exp Dermatol. 2007, 16:421-8. 
 
13. He Y, Ding G, Wang X, Zhu T, Fan S. Calcitonin gene-related peptide in Langerhans cells in 
psoriatic plaque lesions. Chin Med J (Engl). 2000, 113:747-51. 


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14. Riol-Blanco L, Ordovas-Montanes J, Perro M, Naval E, Thiriot A, Alvarez D, Paust S, Wood 
JN, von Andrian UH. Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform 
skin inflammation. Nature. 2014, 510:157-61. 
 
15. Kashem SW, Riedl MS, Yao C, Honda CN, Vulchanova L, Kaplan DH. Nociceptive Sensory 
Fibers Drive Interleukin-23 Production from CD301b+ Dermal Dendritic Cells and Drive 
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