Chronic Pain Master Protocol (CPMP): A Study of LY3016859 in Participants With Diabetic Peripheral Neuropathic Pain

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04476108
• Collaborator: (none)
• Enrollment: 125
• Locations: 36
• Arms: 2
• Actual Duration (Months): 15.9
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study is being done to test the safety and efficacy of the study drug LY3016859 for the treatment of diabetic peripheral neuropathic pain. This trial is part of the chronic pain master protocol (H0P-MC-CPMP) which is a protocol to accelerate the development of new treatments for chronic pain.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Peripheral Neuropathic Pain	Drug: LY3016859; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 125 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomized, Placebo-Controlled, Phase 2 Clinical Trial to Evaluate LY3016859 for the Treatment of Diabetic Peripheral Neuropathic Pain
• Actual Study Start Date: Jul 15, 2020
• Actual Primary Completion Date: Jul 8, 2021
• Actual Study Completion Date: Nov 11, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 750 Mg-500 mg LY3016859 Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg intravenous (IV) infusion for a total of 4 doses.	Drug: LY3016859; Administered IV
Placebo Comparator: Placebo Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Drug: Placebo; Administered IV

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Average Pain Intensity as Measured by the NRS [Baseline, up to Week 8]

   The NRS was used during the preliminary data entry period and daily throughout the study to describe pain severity. Participants were asked to describe their average pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine. Posterior mean change from baseline, 95% credible interval (CrI) was derived using Bayesian mixed model repeated measures.

Secondary Outcome Measures

1. Change From Baseline in the Brief Pain Inventory-Short Form (BPI-SF) Total Interference Score [Baseline, up to Week 8]

   The BPI-SF is a numeric rating scale that assesses the severity of pain (severity scale), its impact on daily functioning (Interference scale), and other aspects of pain (for example, location of pain, relief from medications) in various disease states. BPI-SF score ranges from 0 = no pain to 10 = pain as bad as you can imagine. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures.

2. Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change [Baseline, up to Week 8]

   Patients Global Impression of Change captured the participant's perspective of treatment apart from sub-aspects of the general improvement. This is a numeric scale from 1 to 7: 1 = very much better, and 7 = very much worse. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures.

3. Change From Baseline for Worst Pain Intensity as Measured by NRS [Baseline, up to Week 8]

   The NRS was used during the preliminary data entry period and daily throughout the study to describe pain severity. Participants were asked to describe their worst pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures.

4. Change From Baseline on the Visual Analog Scale (VAS) for Pain [Baseline, up to Week 8]

   VAS was a graphic, single-item scale where participants were asked to describe their pain intensity over the past week, on a scale of 0 to 100: 0 = no pain, and 100 = worst imaginable pain. Participants completed the VAS by placing a line perpendicular to the VAS line at a point that described their pain intensity. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures.

5. Change From Baseline Assessment to Endpoint on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale) [Baseline, up to Week 8]

   The MOS Sleep Scale consists of 12 questions addressing the past week. Participants reported how often each sleep symptom or problem was present on a 5-point categorical scale ranging from 'all of the time' to 'none of the time.' It includes 12 questions with the first question assessing how long it takes the subject to fall asleep. The second question asks how many hours each night the subject slept. The remaining 10 questions have a range of 6 responses from 1="all of the time" to 6="none of the time". MOS Sleep scale scores range from 0 (min) to 100 (max). The original survey items are converted to a 0 to 100 range (by Converting 1 to 0, 2 to 25, 3 to 50, 4 to 75, and 5 to 100). Higher scores represent worse outcomes. Posterior mean change from baseline, 95% CrI was derived using Bayesian longitudinal model.

6. Total Amount of Rescue Medication Use as Measured by Average Dosage Per Week [Baseline up to Week 8]

   Total Amount of Rescue Medication Use as Measured by Average Dosage per Week. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures.

7. Change From Baseline on the EuroQol-5D 5 Level Questionnaire (EQ-5D-5L) (United States) [Baseline, up to Week 8]

   The EQ-5D-5L assessed quality of life based on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participant was asked to 'check the ONE box that best describes your health TODAY,' choosing from 5 options (no problems, slight problems, moderate problems, severe problems, extreme problems) provided under each dimension. The scores in the 5 dimensions were summarized into a health state index score. The health state index value is a single value on a scale from less than 0 to 1 (negative values are valued as worse than death) with higher scores indicating better health: 0 = a health state equivalent to death, and 1 = perfect health. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Have a visual analog scale (VAS) pain value ≥40 and <95 during screening.

• Have a history of daily pain for at least 12 weeks based on participant report or medical history.

• Have a value of ≤30 on the pain catastrophizing scale.

• Have a body mass index <40 kilograms per meter squared (kg/m²) (inclusive).

• Are willing to maintain a consistent regimen of any ongoing nonpharmacologic pain-relieving therapies (for example, physical therapy) and will not start any new nonpharmacologic pain-relieving therapies during study participation.

• Are willing to discontinue all medications taken for chronic pain conditions for the duration of the study.

• Have daily symmetrical foot pain secondary to peripheral neuropathy present for at least 6 months and as diagnosed through use of the Michigan Neuropathy Screening Instrument Part B ≥3 (©University of Michigan).

• Have a history and current diagnosis of type 1 or type 2 diabetes mellitus.

• Have stable glycemic control as indicated by a glycated hemoglobin ≤11 at time of screening.

• Are men, or women able to abide by reproductive and contraceptive requirements.

Exclusion Criteria:

• Have second- or third-degree atrioventricular (AV) heart block or AV dissociation or history of ventricular tachycardia.

• Have had a procedure within the past 6 months intended to produce permanent sensory loss in the target area of interest (for example, ablation techniques).

• Have surgery planned during the study for any reason, related or not to the disease state under evaluation.

• Have, in the judgment of the investigator, an acute, serious, or unstable medical condition or a history or presence of any other medical illness that would preclude study participation.

• There is an inability to rule out other causative or confounding sources of pain in the primary condition under study.

• Have had cancer within 2 years of baseline, except for cutaneous basal cell or squamous cell carcinoma resolved by excision.

• Have a substance use disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (5th edition; DSM-5; American Psychiatric Association).

• Have congenital QT prolongation or QT interval corrected for heart rate using Fridericia's formula (QTcF) interval measurement >450 milliseconds (msec) for male participants, >470 msec for female participants, or >480 msec for participants with bundle branch block.

• Have any clinically important abnormality at screening, as determined by investigator, in physical or neurological examination, vital signs, electrocardiogram (ECG), or clinical laboratory test results that could be detrimental to the participant or could compromise the study.

• Have a positive human immunodeficiency virus (HIV) test result at screening.

• Are, in the judgment of the investigator, actively suicidal and therefore deemed to be at significant risk for suicide.

• Have an intolerance to acetaminophen or paracetamol or any of its excipients.

• Have a history of alcohol, illicit drug, analgesic or narcotic use disorder within 2 years prior to screening.

• Have a current drug-induced neuropathy, for example, due to some types of chemotherapy, or other types of peripheral neuropathy.

• Have known hereditary motor, sensory or autonomic neuropathies.

• Have an estimated glomerular filtration rate (eGFR) of less than 70 milliliters/minute/1.73m² during screening.

• Have any clinically serious or unstable cardiovascular, musculoskeletal disorder, gastrointestinal, endocrinologic, hematologic, hepatic, metabolic, urologic, pulmonary, dermatologic, immunologic, or ophthalmologic disease within 3 months of baseline.

• Have megaloblastic anemia or combined degeneration of the spinal cord.

• Have received any antibodies against nerve growth factor (NGF), or antibodies against EGFR, or EGFR tyrosine kinase inhibitors.

• Have a history of allergic reactions to monoclonal antibodies, or clinically significant multiple or severe drug allergies, including but not limited to erythema multiforme major, linear immunoglobulin A dermatosis, toxic epidermal necrolysis, or exfoliative dermatitis.

• Have a history or presence of uncontrolled asthma, eczema, significant atopy, significant hereditary angio-edema or common variable immune deficiency.

• Have fibromyalgia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Simon Williamson Clinic	Birmingham	Alabama	United States	35211
2	Synexus - US	Chandler	Arizona	United States	85224
3	Synexus Clinical Research - Glendale	Glendale	Arizona	United States	85306
4	Irvine Clinical Research Center	Irvine	California	United States	92614
5	Artemis Institute for Clinical Research	Riverside	California	United States	92503
6	Artemis Institute for Clinical Research	San Diego	California	United States	92103
7	VIN-Julie Schwartzbard	Aventura	Florida	United States	33180
8	Clinical Research of South Florida	Coral Gables	Florida	United States	33134
9	Suncoast Research Group	Miami	Florida	United States	33135
10	Renstar Medical Research	Ocala	Florida	United States	34470
11	Synexus - US	Orlando	Florida	United States	32806
12	Synexus - US	Pinellas Park	Florida	United States	33781
13	Martin E. Hale M.D., P.A.	Plantation	Florida	United States	33317
14	Synexus Clinical Research US, Inc - Orlando	The Villages	Florida	United States	32162
15	Synexus Clinical Research	Chicago	Illinois	United States	60602
16	Northwestern University	Chicago	Illinois	United States	60611
17	Cotton O'Neil Infusion Center	Topeka	Kansas	United States	66606
18	Boston Clinical Trials	Boston	Massachusetts	United States	02131
19	ActivMed Practices and Research	Methuen	Massachusetts	United States	01844
20	MedVadis Research Corporation	Waltham	Massachusetts	United States	02451
21	Great Lakes Research Group, Inc.	Bay City	Michigan	United States	48706
22	StudyMetrix Research	Saint Peters	Missouri	United States	63303
23	Synexus - US	Omaha	Nebraska	United States	68144
24	PharmQuest	Greensboro	North Carolina	United States	27408
25	Synexus - Cincinnati	Cincinnati	Ohio	United States	45236
26	Rapid Medical Research	Cleveland	Ohio	United States	44122
27	Aventiv Research Inc	Columbus	Ohio	United States	43213
28	Altoona Center For Clinical Research	Duncansville	Pennsylvania	United States	16635
29	Clinical Research Center of Reading,LLC	Wyomissing	Pennsylvania	United States	19610
30	Coastal Carolina Research Center	North Charleston	South Carolina	United States	29405
31	Synexus - US	Dallas	Texas	United States	75234
32	Synexus - US	San Antonio	Texas	United States	78229
33	Synexus - US	Murray	Utah	United States	84123
34	Northwest Clinical Research Center	Bellevue	Washington	United States	98007-4209
35	Rainier Clinical Research Center	Renton	Washington	United States	98057
36	Latin Clinical Trial Center	San Juan		Puerto Rico	00909

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 - Mar 27, 2020
• Statistical Analysis Plan - Dec 16, 2021

More Information

Additional Information:

• A Study of LY3016859 in Participants With Diabetic Peripheral Neuropathic Pain

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT04476108
• Other Study ID Numbers: 17535; H0P-MC-NP01
• First Posted: Jul 17, 2020
• Last Update Posted: Aug 3, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neuralgia; Diabetic Neuropathies

Study Results

Participant Flow

Arm/Group Title	750 Mg-500 Milligram (mg) LY3016859	Placebo
Arm/Group Description	Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Period Title: Overall Study
STARTED	84	41
Received at Least 1 Dose of Study Drug	83	41
COMPLETED	76	38
NOT COMPLETED	8	3

Baseline Characteristics

Arm/Group Title	750 Mg-500 mg LY3016859	Placebo	Total
Arm/Group Description	Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.	Total of all reporting groups
Overall Participants	84	41	125
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	50 59.5%	24 58.5%	74 59.2%
>=65 years	34 40.5%	17 41.5%	51 40.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.6 (8.5)	63.3 (8.9)	62.2 (8.7)
Sex: Female, Male (Count of Participants)
Female	35 41.7%	14 34.1%	49 39.2%
Male	49 58.3%	27 65.9%	76 60.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.2%	0 0%	1 0.8%
Asian	1 1.2%	2 4.9%	3 2.4%
Native Hawaiian or Other Pacific Islander	1 1.2%	0 0%	1 0.8%
Black or African American	12 14.3%	4 9.8%	16 12.8%
White	68 81%	33 80.5%	101 80.8%
More than one race	1 1.2%	1 2.4%	2 1.6%
Unknown or Not Reported	0 0%	1 2.4%	1 0.8%
Region of Enrollment (Count of Participants)
United States	84 100%	41 100%	125 100%
Average Pain Intensity as Measured by the Numeric Rating Scale (NRS) (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	5.97 (1.69)	6.30 (1.62)	6.08 (1.66)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Average Pain Intensity as Measured by the NRS
Description	The NRS was used during the preliminary data entry period and daily throughout the study to describe pain severity. Participants were asked to describe their average pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine. Posterior mean change from baseline, 95% credible interval (CrI) was derived using Bayesian mixed model repeated measures.
Time Frame	Baseline, up to Week 8

Outcome Measure Data

Analysis Population Description

All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.

Arm/Group Title	750 Mg-500 mg LY3016859	Placebo
Arm/Group Description	Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Measure Participants	70	38
Mean (95% Confidence Interval) [score on a scale]	-1.98	-1.56

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	750 Mg-500 mg LY3016859
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-0.42
	Confidence Interval	(2-Sided) 95%; -1.17 to 0.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.

2. Secondary Outcome

Title	Change From Baseline in the Brief Pain Inventory-Short Form (BPI-SF) Total Interference Score
Description	The BPI-SF is a numeric rating scale that assesses the severity of pain (severity scale), its impact on daily functioning (Interference scale), and other aspects of pain (for example, location of pain, relief from medications) in various disease states. BPI-SF score ranges from 0 = no pain to 10 = pain as bad as you can imagine. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures.
Time Frame	Baseline, up to Week 8

Outcome Measure Data

Analysis Population Description

All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.

Arm/Group Title	750 Mg-500 mg LY3016859	Placebo
Arm/Group Description	Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Measure Participants	75	38
Mean (95% Confidence Interval) [score on a scale]	-2.11	-1.74

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	750 Mg-500 mg LY3016859, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-0.37
	Confidence Interval	(2-Sided) 95%; -1.09 to 0.35
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.

3. Secondary Outcome

Title	Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change
Description	Patients Global Impression of Change captured the participant's perspective of treatment apart from sub-aspects of the general improvement. This is a numeric scale from 1 to 7: 1 = very much better, and 7 = very much worse. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures.
Time Frame	Baseline, up to Week 8

Outcome Measure Data

Analysis Population Description

All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.

Arm/Group Title	750 Mg-500 mg LY3016859	Placebo
Arm/Group Description	Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Measure Participants	76	38
Mean (95% Confidence Interval) [score on a scale]	2.48	2.75

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	750 Mg-500 mg LY3016859, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-0.27
	Confidence Interval	(2-Sided) 95%; -0.69 to 0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.

4. Secondary Outcome

Title	Change From Baseline for Worst Pain Intensity as Measured by NRS
Description	The NRS was used during the preliminary data entry period and daily throughout the study to describe pain severity. Participants were asked to describe their worst pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures.
Time Frame	Baseline, up to Week 8

Outcome Measure Data

Analysis Population Description

All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.

Arm/Group Title	750 Mg-500 mg LY3016859	Placebo
Arm/Group Description	Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Measure Participants	70	38
Mean (95% Confidence Interval) [score on a scale]	-2.10	-1.66

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	750 Mg-500 mg LY3016859, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-0.44
	Confidence Interval	(2-Sided) 95%; -1.20 to 0.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.

5. Secondary Outcome

Title	Change From Baseline on the Visual Analog Scale (VAS) for Pain
Description	VAS was a graphic, single-item scale where participants were asked to describe their pain intensity over the past week, on a scale of 0 to 100: 0 = no pain, and 100 = worst imaginable pain. Participants completed the VAS by placing a line perpendicular to the VAS line at a point that described their pain intensity. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures.
Time Frame	Baseline, up to Week 8

Outcome Measure Data

Analysis Population Description

All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.

Arm/Group Title	750 Mg-500 mg LY3016859	Placebo
Arm/Group Description	Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Measure Participants	76	38
Mean (95% Confidence Interval) [score on a scale]	-26.17	-23.31

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	750 Mg-500 mg LY3016859, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-2.86
	Confidence Interval	(2-Sided) 95%; -11.71 to 6.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.

6. Secondary Outcome

Title	Change From Baseline Assessment to Endpoint on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale)
Description	The MOS Sleep Scale consists of 12 questions addressing the past week. Participants reported how often each sleep symptom or problem was present on a 5-point categorical scale ranging from 'all of the time' to 'none of the time.' It includes 12 questions with the first question assessing how long it takes the subject to fall asleep. The second question asks how many hours each night the subject slept. The remaining 10 questions have a range of 6 responses from 1="all of the time" to 6="none of the time". MOS Sleep scale scores range from 0 (min) to 100 (max). The original survey items are converted to a 0 to 100 range (by Converting 1 to 0, 2 to 25, 3 to 50, 4 to 75, and 5 to 100). Higher scores represent worse outcomes. Posterior mean change from baseline, 95% CrI was derived using Bayesian longitudinal model.
Time Frame	Baseline, up to Week 8

Outcome Measure Data

Analysis Population Description

All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.

Arm/Group Title	750 Mg-500 mg LY3016859	Placebo
Arm/Group Description	Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Measure Participants	76	38
Mean (95% Confidence Interval) [score on a scale]	0.21	-0.14

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	750 Mg-500 mg LY3016859, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	0.35
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.78
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.

7. Secondary Outcome

Title	Total Amount of Rescue Medication Use as Measured by Average Dosage Per Week
Description	Total Amount of Rescue Medication Use as Measured by Average Dosage per Week. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures.
Time Frame	Baseline up to Week 8

Outcome Measure Data

Analysis Population Description

All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.

Arm/Group Title	750 Mg-500 mg LY3016859	Placebo
Arm/Group Description	Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Measure Participants	70	38
Mean (95% Confidence Interval) [mg per week]	271.58	271.24

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	750 Mg-500 mg LY3016859, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 95%; -188.46 to 187.97
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.

8. Secondary Outcome

Title	Change From Baseline on the EuroQol-5D 5 Level Questionnaire (EQ-5D-5L) (United States)
Description	The EQ-5D-5L assessed quality of life based on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participant was asked to 'check the ONE box that best describes your health TODAY,' choosing from 5 options (no problems, slight problems, moderate problems, severe problems, extreme problems) provided under each dimension. The scores in the 5 dimensions were summarized into a health state index score. The health state index value is a single value on a scale from less than 0 to 1 (negative values are valued as worse than death) with higher scores indicating better health: 0 = a health state equivalent to death, and 1 = perfect health. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures.
Time Frame	Baseline, up to Week 8

Outcome Measure Data

Analysis Population Description

All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.

Arm/Group Title	750 Mg-500 mg LY3016859	Placebo
Arm/Group Description	Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Measure Participants	76	38
Mean (95% Confidence Interval) [score on a scale]	0.07	0.03

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	750 Mg-500 mg LY3016859, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.01 to 0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.

Adverse Events

Time Frame	Baseline through Week 26
Adverse Event Reporting Description	All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Arm/Group Title	750 Mg-500 mg LY3016859		Placebo
Arm/Group Description	Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.		Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
All Cause Mortality
	750 Mg-500 mg LY3016859		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/83 (1.2%)		0/41 (0%)
Serious Adverse Events
	750 Mg-500 mg LY3016859		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/83 (3.6%)		2/41 (4.9%)
Gastrointestinal disorders
Nausea	1/83 (1.2%)	1	0/41 (0%)	0
Vomiting	1/83 (1.2%)	1	0/41 (0%)	0
Infections and infestations
Covid-19 pneumonia	1/83 (1.2%)	1	0/41 (0%)	0
Diabetic foot infection	0/83 (0%)	0	1/41 (2.4%)	1
Injury, poisoning and procedural complications
Adverse event following immunisation	0/83 (0%)	0	1/41 (2.4%)	1
Overdose	1/83 (1.2%)	1	0/41 (0%)	0
Psychiatric disorders
Post-traumatic stress disorder	1/83 (1.2%)	1	0/41 (0%)	0
Other (Not Including Serious) Adverse Events
	750 Mg-500 mg LY3016859		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/83 (33.7%)		12/41 (29.3%)
Gastrointestinal disorders
Abdominal pain upper	0/83 (0%)	0	2/41 (4.9%)	2
Diarrhoea	3/83 (3.6%)	4	0/41 (0%)	0
Nausea	4/83 (4.8%)	4	0/41 (0%)	0
General disorders
Infusion site pain	4/83 (4.8%)	4	0/41 (0%)	0
Xerosis	3/83 (3.6%)	3	0/41 (0%)	0
Infections and infestations
Covid-19	0/83 (0%)	0	3/41 (7.3%)	3
Sinusitis	3/83 (3.6%)	3	0/41 (0%)	0
Investigations
Glomerular filtration rate decreased	0/83 (0%)	0	2/41 (4.9%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	3/83 (3.6%)	3	2/41 (4.9%)	2
Back pain	3/83 (3.6%)	3	0/41 (0%)	0
Muscle spasms	0/83 (0%)	0	2/41 (4.9%)	2
Nervous system disorders
Headache	3/83 (3.6%)	4	1/41 (2.4%)	1
Skin and subcutaneous tissue disorders
Dry skin	3/83 (3.6%)	3	0/41 (0%)	0
Pruritus	4/83 (4.8%)	4	2/41 (4.9%)	2
Rash	6/83 (7.2%)	7	0/41 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.