Rimegepant in Moderate Plaque-type Psoriasis

Psoriasis Clinical Trial

Official title:

A Pilot Study of Rimegepant in Moderate Plaque-type Psoriasis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04629950
• Other study ID #: 20-07022368
• Status: Recruiting
• Phase: Phase 2
• Start date: January 19, 2021
• Est. completion date: August 15, 2024

Study information

• Verified date: August 2023
• Source: Weill Medical College of Cornell University
• Contact: Jennifer T Vu, BS
• Phone: 646-962-7275
• Email: jtv4002[@]med.cornell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: August 15, 2024
• Est. primary completion date: August 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Male or female patients with at least 3% body surface are involved with psoriasis and a PASI score >5.

• Between 18 and 75 years of age.

• Documentation of a definite diagnosis of psoriasis by a dermatologist or biopsy.

• For women of childbearing potential, a negative urine pregnancy test within 48 hours of randomization. Female subjects should not have attempted to become pregnant in the month prior to exposure to rimegepant and agree not to attempt to become pregnant for 8 weeks after exposure to rimegepant.

• A valid form of contraception must be documented for men and women of child-bearing potential.

• The two methods for women of childbearing potential should include:

• One barrier method (for example, Diaphragm with spermicidal gel, condom with spermicidal gel, cervical caps or intrauterine devices placed for at least four weeks before sexual intercourse); AND

• One additional method. The other method could include hormonal contraceptives, or second barrier method as listed above.

• The two options for men of childbearing potential should include:

• Simultaneous use of male condom, and for the female partner, hormonal contraceptives (for example, birth control pills, implants, patch, depot injection, used since at least 4 weeks) or intra-uterine contraceptive device (placed since at least 4 weeks) before sexual intercourse; OR simultaneous use of male condom, and for the female partner, diaphragm with intravaginally applied spermicide.

Exclusion Criteria:

• Any ongoing medical illness or condition that places the participant at higher risk for adverse outcomes or inability to complete study procedures in the opinion of the study investigator.

• Pregnancy or breastfeeding.

• Known autoimmune disorders other than psoriasis.

• Current use of corticosteroids or immunosuppressive medications (for any reason).

• Immunodeficiency diseases.

• Use of any biologic agent/monoclonal antibody within 5 half-lifes prior to baseline.

• Ultraviolet light treatment, cyclosporine, oral corticosteroids, methotrexate, oral retinoids, mycophenolate mofetil, thioguanine, hydroxyurea, sirolimus or azathioprine within the 4 weeks prior to baseline or had topical psoriasis treatment within the previous 2 weeks prior to baseline.

• Participation in another clinical trial involving an investigational drug within the last 30 days prior to baseline.

• Inability for woman of child-bearing potential to use an effective form of contraception if sexually active.

• Use of any medication that is a strong or moderate inhibitor of CYP3A, a strong or moderate inducer of CYP3A, or an inhibitor of glycoprotein (P-gp) or Breast Cancer Resistance Protein (BCRP). Please see Section 7.8 for more information.

• Subject history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. Subjects with myocardial infarction (MI), acute coronary syndrome (ACS), percutaneous coronary intervention (PCI), cardiac surgery, stroke or transient ischemic attack (TIA) during 6 months (24 weeks) prior to screening.

• Uncontrolled hypertension or uncontrolled diabetes (however, subjects can be included who have stable hypertension and/or diabetes for 3 months (12 weeks) prior to screening). Blood pressure greater than 150 mm Hg systolic or 100 mm Hg diastolic after 10 minutes of rest is exclusionary

• Subjects with an active episode of major depressive episode within the last 6 months are ineligible. Subjects with major depressive disorder or any anxiety disorder are eligible only if they are on stable medication for each disorder for at least 3 months prior to the Screening visit.

• Subject has a history or diagnosis of Gilbert's Syndrome or any other active hepatic or biliary disorder

• Hematologic or solid malignancy diagnosis within 5 years prior to screening. Subjects with a history of localized basal cell or squamous cell skin cancer are eligible for the study if they are cancer-free prior to the screening visit in this study.

• Subject has current diagnosis of major depressive disorder requiring treatment with atypical antipsychotics, schizophrenia, bipolar disorder, or borderline personality disorder.

• History of gallstones.

• Subject has current diagnosis of major depressive disorder requiring treatment with atypical antipsychotics, schizophrenia, bipolar disorder, or borderline personality disorder.

• The use of CGRP antagonists (biologic [e.g. Aimovig™, Emgality® and Ajovy™, VyeptiTM] or small molecule [ e.g. Ubrelvy™ {ubrogepant]]) other than rimegepant is prohibited during the study.

• Concomitant use of atypical antipsychotics such as Abilify (aripiprazole), Zyprexa (olanzapine), Seroquel (quetiapine), Geodon (ziprasidone), or Risperdal (risperidone).

• Depakote/Depakene (divalproex/valproic acid/valproate) is prohibited during the study.

• Concomitant use of LAMICTAL (lamotrigine) is prohibited during the study.

• Concomitant use of Modafinil (PROVIGIL®) is prohibited during the study.

• Exclusionary screening lab test findings:

• Serum bilirubin (Total, Direct or Indirect) > 1 x ULN (Only abnormal values of between 1-1.5x ULN may be repeated once for assessment of eligibility prior to randomization)

• AST or ALT > 1 x ULN (Only abnormal values of between 1-1.5x ULN may be repeated once for assessment of eligibility prior to randomization)

• Neutrophil count = 1000/µL (or equivalent)

• HbA1c > 6.5%

Related Conditions & MeSH terms

• Psoriasis

Intervention

Drug:
• Rimegepant
Active Agent
• Placebo
Placebo Comparator

Locations

Country	Name	City	State
United States	Sadick Dermatology	New York	New York
United States	Weill Cornell Medicine	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	Pfizer

Country where clinical trial is conducted

United States, 

References & Publications (15)

Aschenbeck KA, Hordinsky MK, Kennedy WR, Wendelschafer-Crabb G, Ericson ME, Kavand S, Bertin A, Dykstra DD, Panoutsopoulou IG. Neuromodulatory treatment of recalcitrant plaque psoriasis with onabotulinumtoxinA. J Am Acad Dermatol. 2018 Dec;79(6):1156-1159. doi: 10.1016/j.jaad.2018.07.058. No abstract available. — View Citation

Ding W, Stohl LL, Xu L, Zhou XK, Manni M, Wagner JA, Granstein RD. Calcitonin Gene-Related Peptide-Exposed Endothelial Cells Bias Antigen Presentation to CD4+ T Cells toward a Th17 Response. J Immunol. 2016 Mar 1;196(5):2181-94. doi: 10.4049/jimmunol.1500303. Epub 2016 Feb 1. Erratum In: J Immunol. 2023 May 15;210(10):1621-1622. — View Citation

Farber EM, Lanigan SW, Boer J. The role of cutaneous sensory nerves in the maintenance of psoriasis. Int J Dermatol. 1990 Jul-Aug;29(6):418-20. doi: 10.1111/j.1365-4362.1990.tb03825.x. — View Citation

Greb JE, Goldminz AM, Elder JT, Lebwohl MG, Gladman DD, Wu JJ, Mehta NN, Finlay AY, Gottlieb AB. Psoriasis. Nat Rev Dis Primers. 2016 Nov 24;2:16082. doi: 10.1038/nrdp.2016.82. — View Citation

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 Aug;113(8):747-51. — View Citation

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 Protective Cutaneous Immunity. Immunity. 2015 Sep 15;43(3):515-26. doi: 10.1016/j.immuni.2015.08.016. Erratum In: Immunity. 2015 Oct 20;43(4):830. — View Citation

Kaushik SB, Lebwohl MG. Review of safety and efficacy of approved systemic psoriasis therapies. Int J Dermatol. 2019 Jun;58(6):649-658. doi: 10.1111/ijd.14246. Epub 2018 Sep 23. — View Citation

Ostrowski SM, Belkadi A, Loyd CM, Diaconu D, Ward NL. Cutaneous denervation of psoriasiform mouse skin improves acanthosis and inflammation in a sensory neuropeptide-dependent manner. J Invest Dermatol. 2011 Jul;131(7):1530-8. doi: 10.1038/jid.2011.60. Epub 2011 Apr 7. — View Citation

Perlman HH. Remission of psoriasis vulgaris from the use of nerve-blocking agents. Arch Dermatol. 1972 Jan;105(1):128-9. doi: 10.1001/archderm.1972.01620040088028. No abstract available. — View Citation

Racz E, Prens EP. Phototherapy of Psoriasis, a Chronic Inflammatory Skin Disease. Adv Exp Med Biol. 2017;996:287-294. doi: 10.1007/978-3-319-56017-5_24. — View Citation

Rajguru JP, Maya D, Kumar D, Suri P, Bhardwaj S, Patel ND. Update on psoriasis: A review. J Family Med Prim Care. 2020 Jan 28;9(1):20-24. doi: 10.4103/jfmpc.jfmpc_689_19. eCollection 2020 Jan. — View Citation

Reich A, Orda A, Wisnicka B, Szepietowski JC. Plasma concentration of selected neuropeptides in patients suffering from psoriasis. Exp Dermatol. 2007 May;16(5):421-8. doi: 10.1111/j.1600-0625.2007.00544.x. — View Citation

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 Jun 5;510(7503):157-61. doi: 10.1038/nature13199. Epub 2014 Apr 23. — View Citation

Takeshita J, Grewal S, Langan SM, Mehta NN, Ogdie A, Van Voorhees AS, Gelfand JM. Psoriasis and comorbid diseases: Implications for management. J Am Acad Dermatol. 2017 Mar;76(3):393-403. doi: 10.1016/j.jaad.2016.07.065. — View Citation

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 Jun;17(3):257-63. doi: 10.1007/s40257-016-0183-7. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Severity of Psoriasis as Measured with the Psoriasis Area and Severity Index (PASI) Instrument	Total score of Psoriasis Area and Severity Index ranges from 0 to 72. Change = (Week 16 score - Baseline score). A low score means less severe disease while a high score reflects more severe disease. A score of 0 means no psoriasis. A PASI score of 5 to 10 is considered moderate disease and a score over 10 is considered severe. A score over 40 is rare.	Baseline and Week 16
Secondary	Average Change in Psoriasis Area and Severity Index Instrument Score	To Score Whether the Average PASI Score Improves by at Least 50% by Week 16 (Week 16 average score - Baseline average score) PASI range is 0-72 although PASI must be at least 5 for entry into the study. A score of 0 means no psoriasis. A PASI score of 5 to 10 is considered moderate disease and a score over 10 is considered severe. A score over 40 is rare.	Baseline and Week 16
Secondary	Change in Severity of Psoriasis as Assessed by the Investigator's Global Assessment Instrument.	Score of the Investigator's Global Assessment instrument ranges from 0 to 4.; Average Change in Score of Each Group= (Week 16 average score - Baseline average score) 0=Clear, 1=Almost Clear, 2=Mild, 3=Moderate, 4=Severe.	Baseline and Week 16
Secondary	Change in Dermatology Quality of Life Index	Dermatology Quality of Life Index score ranges from 0-30. Average Change in Score of Each Group= (Week 16 average score - Baseline average score). 0 - 1 no effect at all on patient's life, 2 - 5 small effect on patient's life, 6 - 10 moderate effect on patient's life, 11 - 20 very large effect on patient's life, 21 - 30 extremely large effect on patient's life.	Baseline and Week 16
Secondary	Change in Degree of Itching Assessed by the Visual Analogue Scale	The Visual Analogue Scale ranges from 0 to 10. 0= no pruritus, < 3= mild pruritus, = 3-<7= moderate pruritus, = 7-<9 = severe pruritus, = 9= very severe pruritus.	Baseline and Week 16