Study of Ixekizumab in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03848403
• Collaborator: (none)
• Enrollment: 70
• Locations: 2
• Arms: 3
• Actual Duration (Months): 5.6
• Patients Per Site: 35
• Patients Per Site Per Month: 6.3

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the tolerability of injections of each of 3 formulations of ixekizumab using a prefilled syringe. Information about any side effects (including injection site reactions [ISRs]) will be collected.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Biological: Ixekizumab	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: A Randomized Study to Investigate Injection-Site Pain Following Subcutaneous Injections of 2 Ixekizumab Test Formulations Compared to the Commercial Formulation Using a Pre-filled Syringe in Healthy Subjects
• Actual Study Start Date: Jan 29, 2019
• Actual Primary Completion Date: Jul 18, 2019
• Actual Study Completion Date: Jul 18, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ixekizumab (Reference) Reference formulation 80 milligram (mg) ixekizumab administered as a subcutaneous (SC) injection in a prefilled syringe in one of three study periods.	Biological: Ixekizumab; Administered SC; Other Names: LY2439821
Experimental: Ixekizumab (Test 1) Test 1 formulation 80 mg ixekizumab administered as an SC injection in a prefilled syringe in one of three study periods.	Biological: Ixekizumab; Administered SC; Other Names: LY2439821
Experimental: Ixekizumab (Test 2) Test 2 formulation 80 mg ixekizumab administered as an SC injection in a prefilled syringe in one of three study periods.	Biological: Ixekizumab; Administered SC; Other Names: LY2439821

Outcome Measures

Primary Outcome Measures

1. Injection Pain Visual Analog Scale (VAS) Score [Day 1, 8, and 15: Immediately (within 1 minute) after injection]

   The injection pain VAS score is a participant administered single item scale designed to measure pain using a 0-100 millimeter (mm) horizontal VAS. The severity of pain was categorized by VAS pain score as: no pain (0), mild pain ≤ 30, moderate pain (>30 and ≤70), and severe pain (>70). Overall severity of participant's pain is indicated by placing a single mark on the horizontal 100 mm scale from 0 mm (no pain) to 100 mm (worst imaginable pain).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy male participants or female participants who agree not to get pregnant

• Are male participants or female participants with chronic, stable medical problems that, in the investigator's opinion, will not place the participant at increased risk by participating in the study

Exclusion Criteria:

• Have a significant history of, or current, cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, or hematologic disorders that in the opinion of the investigator poses an unacceptable risk to the participant if participating in the study

• Are allergic or hypersensitive to the study medicine

• Have dullness or loss of sensitivity on either side of your abdomen

• Have any condition that could affect pain perception from an injection

• Had a vaccination with a live vaccine within 12 months prior to the first check-in or intend to get a vaccine for tuberculosis within 12 months of completing treatment on this study

• Have any type of hepatitis, human immunodeficiency virus (HIV) infection, or other serious infection

• Show evidence of active or latent tuberculosis (TB)

• Presence of significant neuropsychiatric disorder or a recent history of depression

• Have excessive tattoos or scars over the abdomen or other factors such as rash or excessive folds of skin that would interfere with injection site assessments

• Have had any active or recent infection within 4 weeks of Day 1 that, in the opinion of the investigator would pose an unacceptable risk to the participant if participating in the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Covance	Dallas	Texas	United States	75247-4989
2	Covance Clinical Research Inc	Madison	Wisconsin	United States	53704

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)

• Study Protocol - May 30, 2019
• Statistical Analysis Plan - Jan 8, 2019

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03848403
• Other Study ID Numbers: 17139; I1F-MC-RHCS
• First Posted: Feb 20, 2019
• Last Update Posted: Nov 24, 2020
• Last Verified: Jan 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
• Additional relevant MeSH terms: Ixekizumab

Study Results

Participant Flow

Pre-assignment Detail	Participants were randomized to a treatment sequence in one of three periods. The study was stopped for some participants per sponsor decision and these participants did not move on to subsequent periods in the study at the protocol interim analysis.

Arm/Group Title	Sequence 1: ABC	Sequence 2: BCA	Sequence 3: CAB
Arm/Group Description	A: Reference formulation 80 milligram (mg) of Ixekizumab administered as a subcutaneous (SC) injection in a prefilled syringe in Period 1. B: Test 1 formulation 80 mg of Ixekizumab administered as an subcutaneous SC injection in a prefilled syringe in Period 2. C: Test 2 formulation 80 mg of Ixekizumab administered as an SC injection in a prefilled syringe in Period 3. Sequence 1: ABC (Reference, Test 1, then Test 2)	B: Test 1 formulation 80 mg of Ixekizumab administered as an SC injection in a prefilled syringe in Period 1. C: Test 2 formulation 80 mg of Ixekizumab administered as a SC injection in a prefilled syringe in Period 2. A: Reference formulation 80 mg of Ixekizumab administered as a SC injection in a prefilled syringe in Period 3. Sequence 2: BCA (Test 1, Test 2, Then Reference)	C: Test 2 formulation 80 mg of Ixekizumab administered as an SC injection in a prefilled syringe in Period 1. A: Reference: formulation 80 mg of Ixekizumab administered as a SC injection in a prefilled syringe in Period 2. B: Test 1 formulation 80 mg of Ixekizumab administered as an SC injection in a prefilled syringe in Period 3. Sequence 3: CAB (Test 2, Reference, Then Test 1)
Period Title: Period 1 (Day 1)
STARTED	24	24	22
Received Intervention	24	24	22
COMPLETED	24	24	22
NOT COMPLETED	0	0	0
Period Title: Period 1 (Day 1)
STARTED	24	24	22
Received at Least One Dose of Study Drug	24	24	22
COMPLETED	15	15	15
NOT COMPLETED	9	9	7
Period Title: Period 1 (Day 1)
STARTED	15	15	15
COMPLETED	15	15	15
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	All randomized participants who received at least one 80 milligram (mg) dose of ixekizumab administered as an SC injection in a prefilled syringe in one of three periods.
Overall Participants	70
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	44.5 (13.5)
Sex: Female, Male (Count of Participants)
Female	37 52.9%
Male	33 47.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 15.7%
Not Hispanic or Latino	59 84.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 2.9%
Asian	6 8.6%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	20 28.6%
White	41 58.6%
More than one race	1 1.4%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	70 100%

Outcome Measures

1. Primary Outcome

Title	Injection Pain Visual Analog Scale (VAS) Score
Description	The injection pain VAS score is a participant administered single item scale designed to measure pain using a 0-100 millimeter (mm) horizontal VAS. The severity of pain was categorized by VAS pain score as: no pain (0), mild pain ≤ 30, moderate pain (>30 and ≤70), and severe pain (>70). Overall severity of participant's pain is indicated by placing a single mark on the horizontal 100 mm scale from 0 mm (no pain) to 100 mm (worst imaginable pain).
Time Frame	Day 1, 8, and 15: Immediately (within 1 minute) after injection

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug in a treatment sequence.

Arm/Group Title	Ixekizumab (Reference)	Ixekizumab (Test 1)	Ixekizumab (Test 2)
Arm/Group Description	Reference formulation ixekizumab 80 mg administered as a subcutaneous (SC) injection in a prefilled syringe in one of three study periods.	Test 1 formulation ixekizumab 80 mg administered as an SC injection in a prefilled syringe in one of three study periods.	Test 2 formulation ixekizumab administered as an SC injection in a prefilled syringe in one of three study periods.
Measure Participants	61	63	61
Mean (Standard Deviation) [millimeter (mm)]	25.3 (24.7)	3.3 (7.0)	4.1 (8.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab (Reference), Ixekizumab (Test 1)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Means Difference
	Estimated Value	-21.69
	Confidence Interval	(2-Sided) 95%; -26.90 to -16.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab (Reference), Ixekizumab (Test 2)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	-21.14
	Confidence Interval	(2-Sided) 95%; -26.39 to -15.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ixekizumab (Test 1), Ixekizumab (Test 2)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8341
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Means Difference
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95%; -4.65 to 5.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Up to 85 Days
Adverse Event Reporting Description	All randomized participants who received at least one dose of intervention.
Arm/Group Title	Ixekizumab (Reference)		Ixekizumab (Test 1)		Ixekizumab (Test 2)
Arm/Group Description	Reference formulation 80 mg ixekizumab administered as a subcutaneous (SC) injection in a prefilled syringe in one of three study periods.		Test 1 formulation ixekizumab 80mg administered as an SC injection in a prefilled syringe in one of three study periods.		Test 2 formulation ixekizumab 80 mg administered as an SC injection in a prefilled syringe in one of three study periods.
All Cause Mortality
	Ixekizumab (Reference)		Ixekizumab (Test 1)		Ixekizumab (Test 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/61 (0%)		0/63 (0%)		0/61 (0%)
Serious Adverse Events
	Ixekizumab (Reference)		Ixekizumab (Test 1)		Ixekizumab (Test 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/61 (0%)		0/63 (0%)		0/61 (0%)
Other (Not Including Serious) Adverse Events
	Ixekizumab (Reference)		Ixekizumab (Test 1)		Ixekizumab (Test 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/61 (4.9%)		5/63 (7.9%)		6/61 (9.8%)
General disorders
Injection site reaction	3/61 (4.9%)	3	5/63 (7.9%)	7	6/61 (9.8%)	8

Limitations/Caveats

At protocol-specified interim analysis, the sponsor decided to stop trial.

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.