A Study of the Early Activity of Ixekizumab (LY2439821) in Moderate-to-Severe Psoriasis

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02387801
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arms: 2
• Duration (Months): 16
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

To detect onset of activity of ixekizumab in participants with moderate-to-severe plaque psoriasis and to document the same using sequential photographic images.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis	Drug: Ixekizumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Early Onset of Clinical Improvement With Ixekizumab in Patients With Moderate-to-Severe Plaque Psoriasis
• Study Start Date: Apr 1, 2015
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ixekizumab Dosing Q2W 160 milligrams (mg) ixekizumab given as two subcutaneous (SC) injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once (Q2W) every 2 weeks through week 12. After week 12 participants will receive 80 mg ixekizumab every 4 weeks through week 44.	Drug: Ixekizumab; Administered SC; Other Names: LY2439821
Experimental: Ixekizumab Dosing Q4W 160 mg ixekizumab given as two SC injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once (Q4W) every 4 weeks through week 44.	Drug: Ixekizumab; Administered SC; Other Names: LY2439821

Outcome Measures

Primary Outcome Measures

1. Time to at Least a 1 Point Improvement on the Patient's Global Assessment of Disease Severity (PatGA) Score [Baseline through Week 12]

   The PatGA is a patient-administered single-item scale on which participants are asked to rank by selecting a number on a 0 to 5 Numeric Rating Score (NRS) the severity of their psoriasis "today" from 0 (Clear) = no psoriasis to 5 (Severe) = the worst their psoriasis has ever been.

Secondary Outcome Measures

1. Mean Change From Baseline on Itch Numeric Rating Scale (NRS) Score [Baseline, Week 12]

   The Itch NRS is a patient-administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching from psoriasis (Ps) is indicated by circling the number that best describes the worst level of itching in the past 24 hours. Least Square Means (LS means) are from analysis of mixed-effects model for repeated measures (MMRM) and model includes treatment group, baseline value and timepoint.

2. Mean Change From Baseline on the Dermatology Life Quality Index (DLQI) [Baseline, Week 12]

   The DLQI is a simple, patient-administered, 10-question, validated, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include "Not at all," "A little," "A lot," and "Very much," with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of "Not relevant" which is scored as "0". For all questions, if unanswered the question is scored as "0". Totals range from 0 to 30 (less to more impairment). LS means are from analysis of MMRM and model includes treatment group, baseline value and timepoint.

3. Mean Change From Baseline in Percent Body Surface Area (%BSA) [Baseline, Week 12]

   The BSA is the percentage involvement of psoriasis on each participant's body surface on a continuous scale from 0% (no involvement) to 100% (full involvement), in which 1% corresponds to the size of the participant's hand (including the palm, fingers, and thumb). The total BSA affected was the summation of individual regions affected. LS means are from analysis of MMRM and the model includes treatment group, baseline value, visit and treatment-by-visit interaction

4. Mean Change From Baseline on the Psoriasis Area and Severity Index (PASI) [Baseline, Week 12]

   The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation (scaling), erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Participants achieving PASI 75 were defined as having an improvement of at least 75% in PASI scores compared to baseline. LS means are from analysis of MMRM and the model includes treatment group, baseline value, visit and treatment-by-visit interaction.

5. Time to at Least a 2 Point Improvement on the PatGA Score [Baseline though Week 12]

   The PatGA is a patient-administered single-item scale on which participants are asked to rank by selecting a number on a 0 to 5 NRS the severity of their psoriasis "today" from 0 (Clear) = no psoriasis to 5 (Severe) = the worst their psoriasis has ever been.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Present with chronic moderate-to-severe plaque psoriasis based on a confirmed (by a dermatologist) diagnosis of chronic plaque psoriasis for at least 6 months prior to baseline

• Active psoriatic skin lesions of plaque psoriasis (Ps)

• Are a candidate for phototherapy and/or systemic therapy

• Men must agree to use a reliable method of birth control or remain abstinent during the study and for at least 12 weeks after stopping treatment

• Women must agree to use reliable birth control or remain abstinent during the study and for at least 12 weeks after stopping treatment

Exclusion Criteria:

• Are unable to commit to the photography schedule for the duration of the study

• Have participated in any study with interleukin 17 (IL-17) or (IL-23) antagonists, including ixekizumab

• Serious disorder or illness other than psoriasis

• Serious infection within the last 3 months

• Breastfeeding or nursing (lactating) women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mount Sinai School of Medicine Dermatology Clinical Trials	New York	New York	United States	10029

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

• Khattri S, Goldblum O, Solotkin K, Amir Y, Min MS, Ridenour T, Yang FE, Lebwohl M. Early Onset of Clinical Improvement with Ixekizumab in a Randomized, Open-label Study of Patients with Moderate-to-severe Plaque Psoriasis. J Clin Aesthet Dermatol. 2018 May;11(5):33-37. Epub 2018 May 1.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02387801
• Other Study ID Numbers: 15454; I1F-US-RHBO
• First Posted: Mar 13, 2015
• Last Update Posted: Sep 18, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Psoriasis; Ixekizumab

Study Results

Participant Flow

Recruitment Details	Induction Dosing Period (Weeks 0 up to 12), Maintenance Dosing Period (Weeks 12 up to 48), Minimum Post Treatment Follow-Up Period up to 12 weeks after last visit.
Pre-assignment Detail	Participants were randomized to ixekizumab (ixe) 80 mg Q2W or Q4W during the Induction Dosing Period from Week 0 to Week 12. Participants received ixe Q4W in the Maintenance Dosing Period from Week 12 to Week 48, and then to the Post Follow up Treatment Period for at least 12 weeks.

Arm/Group Title	Ixekizumab Q2W	Ixekizumab Q4W
Arm/Group Description	160 milligrams (mg) ixekizumab given as two subcutaneous (SC) injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once (Q2W) every 2 weeks through week 12. After week 12 participants will receive 80 mg ixekizumab every 4 weeks through week 44.	160 mg ixekizumab given as two SC injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once (Q4W) every 4 weeks through week 44.
Period Title: Induction Dosing Period
STARTED	6	6
COMPLETED	6	6
NOT COMPLETED	0	0
Period Title: Induction Dosing Period
STARTED	0	12
COMPLETED	0	12
NOT COMPLETED	0	0
Period Title: Induction Dosing Period
STARTED	0	12
COMPLETED	0	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Ixekizumab Q2W	Ixekizumab Q4W	Total
Arm/Group Description	160 mg ixekizumab given as two SC injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once Q2W through week 12. After week 12 participants will receive 80 mg ixekizumab every 4 weeks through week 44.	160 mg ixekizumab given as two SC injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once Q4W through week 44.	Total of all reporting groups
Overall Participants	6	6	12
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.8 (12.54)	55.2 (7.39)	48.5 (12.03)
Sex: Female, Male (Count of Participants)
Female	1 16.7%	3 50%	4 33.3%
Male	5 83.3%	3 50%	8 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 16.7%	2 33.3%	3 25%
Not Hispanic or Latino	5 83.3%	4 66.7%	9 75%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 16.7%	0 0%	1 8.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 16.7%	1 16.7%	2 16.7%
White	4 66.7%	5 83.3%	9 75%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	6 100%	6 100%	12 100%

Outcome Measures

1. Primary Outcome

Title	Time to at Least a 1 Point Improvement on the Patient's Global Assessment of Disease Severity (PatGA) Score
Description	The PatGA is a patient-administered single-item scale on which participants are asked to rank by selecting a number on a 0 to 5 Numeric Rating Score (NRS) the severity of their psoriasis "today" from 0 (Clear) = no psoriasis to 5 (Severe) = the worst their psoriasis has ever been.
Time Frame	Baseline through Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	Ixekizumab Q2W	Ixekizumab Q4W
Arm/Group Description	160 mg ixekizumab given as two SC injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once Q2W through week 12. After week 12 participants will receive 80 mg ixekizumab every 4 weeks through week 44.	160 mg ixekizumab given as two SC injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once Q4W through week 44.
Measure Participants	6	6
Median (90% Confidence Interval) [Days]	5.0	6.0

2. Secondary Outcome

Title	Mean Change From Baseline on Itch Numeric Rating Scale (NRS) Score
Description	The Itch NRS is a patient-administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching from psoriasis (Ps) is indicated by circling the number that best describes the worst level of itching in the past 24 hours. Least Square Means (LS means) are from analysis of mixed-effects model for repeated measures (MMRM) and model includes treatment group, baseline value and timepoint.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	Ixekizumab Q2W	Ixekizumab Q4W
Arm/Group Description	160 mg ixekizumab given as two SC injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once Q2W through week 12. After week 12 participants will receive 80 mg ixekizumab every 4 weeks through week 44.	160 mg ixekizumab given as two SC injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once Q4W through week 44.
Measure Participants	6	6
Least Squares Mean (Standard Error) [units on a scale]	-6.2 (0.53)	-6.6 (0.55)

3. Secondary Outcome

Title	Mean Change From Baseline on the Dermatology Life Quality Index (DLQI)
Description	The DLQI is a simple, patient-administered, 10-question, validated, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include "Not at all," "A little," "A lot," and "Very much," with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of "Not relevant" which is scored as "0". For all questions, if unanswered the question is scored as "0". Totals range from 0 to 30 (less to more impairment). LS means are from analysis of MMRM and model includes treatment group, baseline value and timepoint.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	Ixekizumab Q2W	Ixekizumab Q4W
Arm/Group Description	160 mg ixekizumab given as two SC injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once Q2W through week 12. After week 12 participants will receive 80 mg ixekizumab every 4 weeks through week 44.	160 mg ixekizumab given as two SC injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once Q4W through week 44.
Measure Participants	6	6
Least Squares Mean (Standard Error) [units on a scale]	-13.4 (1.56)	-14.3 (1.59)

4. Secondary Outcome

Title	Mean Change From Baseline in Percent Body Surface Area (%BSA)
Description	The BSA is the percentage involvement of psoriasis on each participant's body surface on a continuous scale from 0% (no involvement) to 100% (full involvement), in which 1% corresponds to the size of the participant's hand (including the palm, fingers, and thumb). The total BSA affected was the summation of individual regions affected. LS means are from analysis of MMRM and the model includes treatment group, baseline value, visit and treatment-by-visit interaction
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	Ixekizumab Q2W	Ixekizumab Q4W
Arm/Group Description	160 mg ixekizumab given as two SC injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once Q2W through week 12. After week 12 participants will receive 80 mg ixekizumab every 4 weeks through week 44.	160 mg ixekizumab given as two SC injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once Q4W through week 44.
Measure Participants	6	6
Least Squares Mean (Standard Error) [percentage of body surface area]	-26.1 (1.39)	-28.0 (1.39)

5. Secondary Outcome

Title	Mean Change From Baseline on the Psoriasis Area and Severity Index (PASI)
Description	The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation (scaling), erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Participants achieving PASI 75 were defined as having an improvement of at least 75% in PASI scores compared to baseline. LS means are from analysis of MMRM and the model includes treatment group, baseline value, visit and treatment-by-visit interaction.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	Ixekizumab Q2W	Ixekizumab Q4W
Arm/Group Description	160 mg ixekizumab given as two SC injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once Q2W through week 12. After week 12 participants will receive 80 mg ixekizumab every 4 weeks through week 44.	160 mg ixekizumab given as two SC injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once Q4W through week 44.
Measure Participants	6	6
Least Squares Mean (Standard Error) [units on a scale]	-22.00 (0.456)	-22.72 (0.456)

6. Secondary Outcome

Title	Time to at Least a 2 Point Improvement on the PatGA Score
Description	The PatGA is a patient-administered single-item scale on which participants are asked to rank by selecting a number on a 0 to 5 NRS the severity of their psoriasis "today" from 0 (Clear) = no psoriasis to 5 (Severe) = the worst their psoriasis has ever been.
Time Frame	Baseline though Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	Ixekizumab Q2W	Ixekizumab Q4W
Arm/Group Description	160 mg ixekizumab given as two SC injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once Q2W through week 12. After week 12 participants will receive 80 mg ixekizumab every 4 weeks through week 44.	160 mg ixekizumab given as two SC injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once Q4W through week 44.
Measure Participants	6	6
Median (90% Confidence Interval) [Days]	10.0	13.5

Adverse Events

Arm/Group Title	Ixekizumab Q2W Induction Dosing Period		Ixekizumab Q4W Induction Dosing Period		Ixekizumab 80 mg Q4W Maintenance		Ixekizumab 80 mg Q4W Post-treatment
Arm/Group Description	160 mg ixekizumab given as two SC injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once Q2W through week 12. After week 12 participants will receive 80 mg ixekizumab every 4 weeks through week 44.		160 mg ixekizumab given as two SC injections at week 0 followed by 80 mg ixekizumab given as a single SC injection once Q4W through week 44.		After week 12 all participants are given 80 mg ixekizumab as a single SC injection once Q4W through week 44.		All participants receiving at least one dose of ixekizumab entered the post treatment follow-up period for a minimum of 12 weeks.
All Cause Mortality
	Ixekizumab Q2W Induction Dosing Period		Ixekizumab Q4W Induction Dosing Period		Ixekizumab 80 mg Q4W Maintenance		Ixekizumab 80 mg Q4W Post-treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ixekizumab Q2W Induction Dosing Period		Ixekizumab Q4W Induction Dosing Period		Ixekizumab 80 mg Q4W Maintenance		Ixekizumab 80 mg Q4W Post-treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Ixekizumab Q2W Induction Dosing Period		Ixekizumab Q4W Induction Dosing Period		Ixekizumab 80 mg Q4W Maintenance		Ixekizumab 80 mg Q4W Post-treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/6 (83.3%)		5/6 (83.3%)		9/12 (75%)		1/12 (8.3%)
Gastrointestinal disorders
Diarrhoea	0/6 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	2	0/12 (0%)	0
Toothache	0/6 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
General disorders
Fatigue	0/6 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Injection site erythema	1/6 (16.7%)	1	1/6 (16.7%)	1	1/12 (8.3%)	3	0/12 (0%)	0
Injection site urticaria	0/6 (0%)	0	2/6 (33.3%)	2	0/12 (0%)	0	0/12 (0%)	0
Infections and infestations
Cellulitis	0/6 (0%)	0	0/6 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1
Hordeolum	0/6 (0%)	0	1/6 (16.7%)	1	0/12 (0%)	0	0/12 (0%)	0
Influenza	0/6 (0%)	0	0/6 (0%)	0	2/12 (16.7%)	2	0/12 (0%)	0
Localised infection	1/6 (16.7%)	1	0/6 (0%)	0	0/12 (0%)	0	0/12 (0%)	0
Skin bacterial infection	0/6 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Upper respiratory tract infection	0/6 (0%)	0	1/6 (16.7%)	1	4/12 (33.3%)	4	0/12 (0%)	0
Investigations
Biopsy breast	0/6 (0%)	0	0/6 (0%)	0	2/12 (16.7%)	2	0/12 (0%)	0
Biopsy prostate	0/5 (0%)	0	1/3 (33.3%)	1	0/8 (0%)	0	0/8 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	2/6 (33.3%)	2	0/6 (0%)	0	0/12 (0%)	0	0/12 (0%)	0
Muscle spasms	0/6 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Skin and subcutaneous tissue disorders
Acne	1/6 (16.7%)	1	0/6 (0%)	0	0/12 (0%)	0	0/12 (0%)	0
Hyperhidrosis	1/6 (16.7%)	1	0/6 (0%)	0	0/12 (0%)	0	0/12 (0%)	0
Pruritus	0/6 (0%)	0	1/6 (16.7%)	1	0/12 (0%)	0	0/12 (0%)	0
Surgical and medical procedures
Eye laser surgery	0/6 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	2	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.