Ixekizumab in the Treatment of Pityriasis Rubra Pilaris (PRP)

15 patients with PRP will be treated with ixekizumab for 24 weeks to determine safety and efficacy. Participants are required to travel to Portland, OR only for the first visit and week-24 visit. 5 visits in between these times and one follow up visit may be performed by secure videoconferencing.

Study Overview

• Status: Completed
• Conditions: Pityriasis Rubra Pilaris
• Intervention / Treatment: Drug: Ixekizumab

Detailed Description

Pityriasis rubra pilaris (PRP) is a rare and poorly understood severe inflammatory skin disease characterized by widespread (often full-body) redness and flaking of the skin, painful thickening and cracking of the palms and soles, hair loss, crumbling nails, and severe skin itching and burning.

There is no FDA-approved therapy for this rare disease and the commonly used medications do not work for many patients. There is some evidence that IL-17 may be too high in the skin of PRP patients. Ixekizumab is an injectable medication that blocks IL-17 and is FDA-approved for psoriasis.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of PRP by clinical assessment and biopsy.
• Male subject age 18-99.
• Female subject age 18-99; either of non-childbearing potential or of childbearing potential who test negative for pregnancy and agree to use a reliable method of birth control or remain abstinent during the study and for at least 12 weeks following the last dose of ixekizumab.
• PASI score of 10 or greater at baseline.
• Are a candidate for phototherapy and/or systemic therapy.
• Willingness to travel to OHSU for all study visits, OR living >30 miles from OHSU and willing/able to participate in remote videoconferencing visits with access to a computer with internet capabilities and webcam.
• Have given written informed consent approved by the OHSU Investigational Review Board.

Exclusion Criteria:

• Known malignancy or lymphoproliferative disease (except treated basal cell skin cancer, treated squamous cell skin cancer, or treated cervical carcinoma in situ) for at least 5 years.
• Active, untreated, acute or chronic infection (such as untreated tuberculosis), or immunocompromised to an extent that such that participation in the study would pose an unacceptable risk to the subject. (Treated infections such as latent tuberculosis after completion of the appropriate therapy are not excluded.)
• Positive for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus.
• Previous treatment with any agent that targets interleukins 17 specifically.
• Systemic treatment or phototherapy for PRP within the past 4 weeks or 5 half-lives prior to baseline, whichever is longer. For biologic therapies, the specific washout periods used will be: etanercept <28 days; infliximab, adalimumab, or alefacept <60 days; golimumab <90 days; ustekinumab <8 months; rituximab or efalizumab <12 months.
• Have a known allergy or hypersensitivity to any biologic therapy that would pose an unacceptable risk to the subject if participating in this study.
• Have a live vaccine within 12 weeks prior to baseline or intend to have a live vaccine during the course of study.
• Had any major surgery within 8 weeks prior to baseline or will require major surgery during the study that, in the opinion of the investigator, would pose an unacceptable risk to the subject.
• Presence of significant uncontrolled cerebrovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, neurologic, or neuropsychiatric disorders, or abnormal laboratory screening values that, in the opinion of the investigator, pose an unacceptable risk to the subject if participating in the study or of interfering with the interpretation of the data.
• Presence of inflammatory bowel disease
• Have clinical laboratory test results at screening that are outside the normal reference range of the population and are considered clinically significant, or have any of the following specific abnormalities: Neutrophil count <1500 cells/µL, lymphocyte count <500 cells/µL, platelet count <100,000 cells/µL, AST or ALT > 2.5 times the upper limit of normal, hemoglobin <8.5 g/dL for male subjects and <8.0 g/dL for female subjects, serum creatinine >2.0 mg/dL.
• Women who are lactating or breastfeeding.
• Have any other condition that precludes the subject from following and completing the protocol, in the opinion of the investigator.
• Are investigator site personnel directly affiliated with this study and/or their immediate families (spouse, parent, child, or sibling).

Are currently enrolled in, or discontinued from a clinical trial involving an investigational product or non-approved use of a drug or device within the last 4 weeks or a period of at least 5 half-lives of the last administration of the drug, whichever is longer, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ixekizumab treatment arm; Ixekizumab 160 mg subcutaneous injection at week 0, followed by 80 mg subcutaneous injections at week 2, 4, 6, 8, 10, 12, 16, and 20	Drug: Ixekizumab; Treatment at the FDA-approved psoriasis dosing; Other Names: Taltz; IL-17A inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Improvement in PRP Severity and Body Surface Area	Clinical improvement will be measured by the Psoriasis Area and Severity Index (PASI) score. PASI is a scale that measures the severity (redness, scale, and elevation) of each body surface area of skin involved in psoriasis (a disease that has some similarities with PRP). Redness, scale, and elevation are each scored on a 0-4 point scale, added together, and multiplied by each body surface area involved (head and neck, trunk, upper limbs, lower limbs). The maximum score is 72 which would indicate the worst disease over every surface of someone's body. A scale of zero would indicate normal skin.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in Quality of Life	Quality of life will be measured by the Dermatology Life Quality Index (DLQI). There are 10 questions covering symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment. Each question refers to the impact of PRP on the patient's life over the previous week. The highest score is 30 and would indicate a maximum (negative) impact on quality of life. A score of zero would indicate no impact on quality of life.	24 weeks
Improvement in Itch	Itch will be measured using a numeric rating scale from 0 (no itch) to 10 (worst itch imaginable).	24 weeks

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: Eli Lilly and Company
• Investigators: Principal Investigator: Teri Greiling, MD, PhD, Oregon Health and Science University

Publications and helpful links

General Publications

• Haynes D, Strunck JL, Topham CA, Ortega-Loayza AG, Kent G, Cassidy PB, Hu R, Choate K, Wang Z, Liu Y, Greiling TM. Evaluation of Ixekizumab Treatment for Patients With Pityriasis Rubra Pilaris: A Single-Arm Trial. JAMA Dermatol. 2020 Jun 1;156(6):668-675. doi: 10.1001/jamadermatol.2020.0932.

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2018
• Primary Completion (Actual): October 14, 2019
• Study Completion (Actual): January 13, 2020

Study Registration Dates

• First Submitted: March 20, 2018
• First Submitted That Met QC Criteria: March 26, 2018
• First Posted (Actual): April 3, 2018

Study Record Updates

• Last Update Posted (Actual): July 1, 2020
• Last Update Submitted That Met QC Criteria: June 15, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: IL-17; Ixekizumab; Pityriasis Rubra Pilaris (PRP)
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Dermatitis; Skin Diseases, Eczematous; Dermatitis, Exfoliative; Pityriasis; Pityriasis Rubra Pilaris; Dermatologic Agents; Ixekizumab
• Other Study ID Numbers: STUDY00018031

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No