Ixekizumab in the Treatment of Pityriasis Rubra Pilaris (PRP)

• Sponsor: Oregon Health and Science University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03485976
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 12
• Location: 1
• Arm: 1
• Actual Duration (Months): 19.7
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pityriasis Rubra Pilaris	Drug: Ixekizumab	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Ixekizumab in the Treatment of Pityriasis Rubra Pilaris (PRP)
• Actual Study Start Date: May 23, 2018
• Actual Primary Completion Date: Oct 14, 2019
• Actual Study Completion Date: Jan 13, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Clinical Improvement in PRP Severity and Body Surface Area [24 weeks]

   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.

Secondary Outcome Measures

1. Improvement in Quality of Life [24 weeks]

   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.

2. Improvement in Itch [24 weeks]

   Itch will be measured using a numeric rating scale from 0 (no itch) to 10 (worst itch imaginable).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Oregon Health and Science University	Portland	Oregon	United States	97239

Sponsors and Collaborators

• Oregon Health and Science University
• Eli Lilly and Company

Investigators

• Principal Investigator: Teri Greiling, MD, PhD, Oregon Health and Science University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 27, 2020

More Information

Publications

None provided.

• Responsible Party: Teri Greiling, Assistant Professor of Dermatology, Oregon Health and Science University
• ClinicalTrials.gov Identifier: NCT03485976
• Other Study ID Numbers: STUDY00018031
• First Posted: Apr 3, 2018
• Last Update Posted: Jul 1, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by Teri Greiling, Assistant Professor of Dermatology, Oregon Health and Science University: Ixekizumab; IL-17; Pityriasis Rubra Pilaris (PRP)
• Additional relevant MeSH terms: Pityriasis; Dermatitis, Exfoliative; Pityriasis Rubra Pilaris; Ixekizumab

Study Results

Participant Flow

Arm/Group Title	Ixekizumab Treatment Arm
Arm/Group Description	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 Ixekizumab: Treatment at the FDA-approved psoriasis dosing
Period Title: Overall Study
STARTED	12
COMPLETED	11
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Ixekizumab Treatment Arm
Arm/Group Description	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 Ixekizumab: Treatment at the FDA-approved psoriasis dosing
Overall Participants	12
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	44.8
Sex: Female, Male (Count of Participants)
Female	4 33.3%
Male	8 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	12 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	12 100%
Body Mass Index (BMI) (kg/m^2) [Median (Full Range) ]
Median (Full Range) [kg/m^2]	28.0
PRP Subtype (Count of Participants)
Classic adult (Type I PRP)	6 50%
Atypical adult (Type II PRP)	5 41.7%
Classic juvenile (Type III PRP)	1 8.3%
Psoriasis Assessment and Severity Index (PASI) score (units on a scale) [Median (Full Range) ]
Median (Full Range) [units on a scale]	24.8
Physician Global Assessment (PGA) score (Count of Participants)
Clear (0)	0 0%
Almost clear (1)	0 0%
Mild (2)	0 0%
Moderate (3)	9 75%
Severe (4)	3 25%
Dermatology Life Quality Index (DLQI) score (units on a scale) [Median (Full Range) ]
Median (Full Range) [units on a scale]	19
Itch Numerical Rating Score (NRS) (units on a scale) [Median (Full Range) ]
Median (Full Range) [units on a scale]	7
Pain Numerical Rating Score (NRS) (units on a scale) [Median (Full Range) ]
Median (Full Range) [units on a scale]	6
Age at PRP diagnosis (years) [Median (Full Range) ]
Median (Full Range) [years]	43.7
Duration of PRP symptoms prior to trial enrollment (months) [Median (Full Range) ]
Median (Full Range) [months]	11.9
Previous systemic therapy (participants) [Number]
Treatment naive	1 8.3%
Prior systemic therapy	11 91.7%
Prior methotrexate	6 50%
Prior systemic retinoid	7 58.3%
Prior biologic therapy	4 33.3%

Outcome Measures

1. Primary Outcome

Title	Clinical Improvement in PRP Severity and Body Surface Area
Description	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.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Mean improvement in PASI from baseline to week-24

Arm/Group Title	Ixekizumab Treatment Arm
Arm/Group Description	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 Ixekizumab: Treatment at the FDA-approved psoriasis dosing
Measure Participants	12
Mean (Standard Error) [units on a scale]	15.2 (2.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab Treatment Arm
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The threshold for statistical significance was p=0.05
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Improvement in Quality of Life
Description	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.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ixekizumab Treatment Arm
Arm/Group Description	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 Ixekizumab: Treatment at the FDA-approved psoriasis dosing
Measure Participants	12
Mean (Standard Error) [units on a scale]	9.5 (2.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab Treatment Arm
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	The threshold for significance was p=0.05
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Improvement in Itch
Description	Itch will be measured using a numeric rating scale from 0 (no itch) to 10 (worst itch imaginable).
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ixekizumab Treatment Arm
Arm/Group Description	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 Ixekizumab: Treatment at the FDA-approved psoriasis dosing
Measure Participants	12
Mean (Standard Error) [units on a scale]	3.6 (0.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab Treatment Arm
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	Threshold for significance was p=0.05
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	24-weeks
Arm/Group Title	Ixekizumab Treatment Arm
Arm/Group Description	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 Ixekizumab: Treatment at the FDA-approved psoriasis dosing
All Cause Mortality
	Ixekizumab Treatment Arm
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Serious Adverse Events
	Ixekizumab Treatment Arm
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Other (Not Including Serious) Adverse Events
	Ixekizumab Treatment Arm
	Affected / at Risk (%)	# Events
Total	8/12 (66.7%)
Blood and lymphatic system disorders
Mild leukopenia	1/12 (8.3%)	1
Eosinophilia	1/12 (8.3%)	1
Cardiac disorders
Non-specific chest pain (resolved without intervention)	1/12 (8.3%)	1
Eye disorders
Glaucoma	1/12 (8.3%)	1
Gastrointestinal disorders
Gastrointestinal upset	1/12 (8.3%)	1
Infections and infestations
Upper respiratory tract infection	4/12 (33.3%)	4
Otitis externa	1/12 (8.3%)	1
Bacterial vaginosis	1/12 (8.3%)	1
Skin and subcutaneous tissue disorders
Injection site reaction	1/12 (8.3%)	1
Temporary worsening of PRP	1/12 (8.3%)	1
Ingrown nail	1/12 (8.3%)	1
Cutaneous atrophy associated with corticosteroid use	1/12 (8.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.