Ixekizumab in the Treatment of Pityriasis Rubra Pilaris (PRP)

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.

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.