Trial Outcomes & Findings for A Study of LY3462817 in Participants With Rheumatoid Arthritis (NCT NCT04634253)

Last Updated: 2023-07-12

Results Overview

Disease Activity Score (DAS) based on a 28 joint count hsCRP consisted of composite numerical score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56\*square root (sqrt) (TJC28) plus (+) 0.28\*sqrt (SJC28)+ 0.014\* participant's global assessment of disease activity + 0.36\*natural log(hsCRP+1) +0.96. Scores ranged 1.0-9.4, where lower scores indicated less disease activity. Least Square Mean (LS Mean) was calculated using mixed model repeated measures (MMRM) with treatment, strata (previous RA therapy population), baseline value, visit, treatment-by-visit interaction as fixed factors.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

98 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2023-07-12

Participant Flow

This is a Phase 2, proof-of-concept, placebo-controlled, double-blind, randomized study. Participants were randomized to receive LY3462817 700 mg, LY3462817 300 mg, or placebo in an allocation ratio of 2:1:1.

Participant milestones

Participant milestones
Measure	Placebo Participants received intravenous (IV) infusion of 0.9% sodium chloride solution (Placebo).	LY3462817 300 mg Participants received IV infusion of 300 milligrams (mg) LY3462817 solution.	LY3462817 700 mg Participants received IV infusion of 700 mg LY3462817 solution.
Overall Study STARTED	24	25	49
Overall Study Received at Least One Dose	24	25	49
Overall Study COMPLETED	22	23	46
Overall Study NOT COMPLETED	2	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received intravenous (IV) infusion of 0.9% sodium chloride solution (Placebo).	LY3462817 300 mg Participants received IV infusion of 300 milligrams (mg) LY3462817 solution.	LY3462817 700 mg Participants received IV infusion of 700 mg LY3462817 solution.
Overall Study Adverse Event	1	1	0
Overall Study Physician Decision	0	1	0
Overall Study Withdrawal by Subject	1	0	3

Baseline Characteristics

A Study of LY3462817 in Participants With Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=24 Participants Participants received IV infusion of 0.9% sodium chloride solution (Placebo).	LY3462817 300 mg n=25 Participants Participants received IV infusion of 300 mg LY3462817 solution.	LY3462817 700 mg n=49 Participants Participants received IV infusion of 700 mg LY3462817 solution.	Total n=98 Participants Total of all reporting groups
Age, Continuous	55.8 years STANDARD_DEVIATION 11.1 • n=5 Participants	50.1 years STANDARD_DEVIATION 15.8 • n=7 Participants	50.5 years STANDARD_DEVIATION 11.2 • n=5 Participants	51.7 years STANDARD_DEVIATION 12.6 • n=4 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	20 Participants n=7 Participants	43 Participants n=5 Participants	82 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	16 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	7 Participants n=5 Participants	10 Participants n=7 Participants	13 Participants n=5 Participants	30 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) White	17 Participants n=5 Participants	15 Participants n=7 Participants	34 Participants n=5 Participants	66 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment Hungary	8 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants	28 Participants n=4 Participants
Region of Enrollment United States	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants	18 Participants n=4 Participants
Region of Enrollment Czechia	0 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Region of Enrollment Poland	5 Participants n=5 Participants	2 Participants n=7 Participants	11 Participants n=5 Participants	18 Participants n=4 Participants
Region of Enrollment Mexico	7 Participants n=5 Participants	10 Participants n=7 Participants	13 Participants n=5 Participants	30 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose and had data for DAS28-hsCRP

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Participants received IV infusion of 0.9% sodium chloride solution (Placebo).	LY3462817 300 mg n=22 Participants Participants received IV infusion of 300 mg LY3462817 solution.	LY3462817 700 mg n=42 Participants Participants received IV infusion of 700 mg LY3462817 solution.
Change From Baseline on the Disease Activity Score Modified to Include the 28 Diarthrodial Joint Count-High-Sensitivity C-Reactive Protein (DAS28-hsCRP)	-0.99 Units on a scale Standard Error 0.261	-1.88 Units on a scale Standard Error 0.249	-2.09 Units on a scale Standard Error 0.184

SECONDARY outcome

Timeframe: Week 12

Population: All randomized participants.

ACR responders are participants with at least 20% improvement from baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index (HAQ-DI) which measures participants perceived degree of difficulty performing daily activities, acute phase reactant as measured by hsCRP, Patient's Assessment of Pain-Visual Analog Scale (Pain-VAS), Patient's Global Assessment of Disease Activity (PaGADA\_VAS), and Physician's Global Assessment of Disease Activity (PhGADA\_VAS).

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants received IV infusion of 0.9% sodium chloride solution (Placebo).	LY3462817 300 mg n=25 Participants Participants received IV infusion of 300 mg LY3462817 solution.	LY3462817 700 mg n=49 Participants Participants received IV infusion of 700 mg LY3462817 solution.
Percentage of Participants Achieving 20% Improvement in American College of Rheumatology Criteria (ACR20)	41.7 Percentage of Participants Interval 21.9 to 61.4	44.0 Percentage of Participants Interval 24.5 to 63.5	71.4 Percentage of Participants Interval 58.8 to 84.1

SECONDARY outcome

Timeframe: Week 12

Population: All randomized participants.

ACR responders are participants with at least 70% improvement from baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index (HAQ-DI) which measures participants perceived degree of difficulty performing daily activities, acute phase reactant as measured by hsCRP, Patient's Assessment of Pain-Visual Analog Scale (Pain-VAS), Patient's Global Assessment of Disease Activity (PaGADA\_VAS), and Physician's Global Assessment of Disease Activity (PhGADA\_VAS).

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants received IV infusion of 0.9% sodium chloride solution (Placebo).	LY3462817 300 mg n=25 Participants Participants received IV infusion of 300 mg LY3462817 solution.	LY3462817 700 mg n=49 Participants Participants received IV infusion of 700 mg LY3462817 solution.
Percentage of Participants Achieving 70% Improvement in American College of Rheumatology Criteria (ACR70)	16.7 Percentage of Participants Interval 1.8 to 31.6	4.0 Percentage of Participants Interval 0.0 to 11.7	20.4 Percentage of Participants Interval 9.1 to 31.7

SECONDARY outcome

Timeframe: Week 12

Population: All randomized participants.

ACR responders are participants with at least 50% improvement from baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index (HAQ-DI) which measures participants perceived degree of difficulty performing daily activities, acute phase reactant as measured by hsCRP, Patient's Assessment of Pain-Visual Analog Scale (Pain-VAS), Patient's Global Assessment of Disease Activity (PaGADA\_VAS), and Physician's Global Assessment of Disease Activity (PhGADA\_VAS).

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Participants received IV infusion of 0.9% sodium chloride solution (Placebo).	LY3462817 300 mg n=25 Participants Participants received IV infusion of 300 mg LY3462817 solution.	LY3462817 700 mg n=49 Participants Participants received IV infusion of 700 mg LY3462817 solution.
Percentage of Participants Achieving 50% Improvement in American College of Rheumatology Criteria (ACR50)	20.8 Percentage of Participants Interval 4.6 to 37.1	20.0 Percentage of Participants Interval 4.3 to 35.7	38.8 Percentage of Participants Interval 25.1 to 52.4

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose and had data for SDAI.

The SDAI is a tool for measurement of disease activity in RA that integrates measures of physical examination, acute phase response, patient self-assessment, and evaluator assessment. The SDAI is calculated by adding together scores from 1) TJC28 (0 to 28), 2) SJC28 (0 to 28), 3) acute phase response using C-reactive protein (0.1 to 10.0 mg/dL), 4) Patient's Global Assessment of Disease Activity using VAS (0 to 10 cm), and 5) Physician's Global Assessment of Disease Activity using VAS (0 to 10 cm). Total Score scale range is 0 (remission) to 86 (high disease activity). LS Mean was calculated using mixed model repeated measures (MMRM) with treatment, strata (previous RA therapy population), baseline value, visit, treatment-by-visit interaction as fixed factors.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Participants received IV infusion of 0.9% sodium chloride solution (Placebo).	LY3462817 300 mg n=21 Participants Participants received IV infusion of 300 mg LY3462817 solution.	LY3462817 700 mg n=42 Participants Participants received IV infusion of 700 mg LY3462817 solution.
Change From Baseline for Mean Simplified Disease Activity Index (SDAI)	-13.80 units on a scale Standard Error 2.664	-25.06 units on a scale Standard Error 2.571	-26.90 units on a scale Standard Error 1.880

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose and had data for CDAI.

The CDAI is a tool for measurement of disease activity in RA that does not require a laboratory component and was scored by the investigative site. It integrates TJC28 (scored 0-28 with higher scores indicating higher disease activity), SJC28 (scored 0-28 with higher scores indicating higher disease activity), Patient's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity), and Physician's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity). The CDAI is calculated by summing the values of the 4 components. CDAI scores range from 0 to 76; lower scores indicated lower disease activity. A negative change from baseline indicates improvement in condition. LS Mean was calculated using MMRM with treatment, strata (previous RA therapy population), baseline value, visit, treatment-by-visit interaction as fixed factors.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Participants received IV infusion of 0.9% sodium chloride solution (Placebo).	LY3462817 300 mg n=21 Participants Participants received IV infusion of 300 mg LY3462817 solution.	LY3462817 700 mg n=44 Participants Participants received IV infusion of 700 mg LY3462817 solution.
Change From Baseline for Mean Clinical Disease Activity Index (CDAI)	-13.75 units on a scale Standard Error 2.709	-24.06 units on a scale Standard Error 2.628	-25.51 units on a scale Standard Error 1.854

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who received at least one dose and had data for MCS and PCS.

The SF-36 is a health-related survey that assesses participant's health status and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health, mental health, social functioning, and vitality. The 8 domains are combined to form 2 component scores mental (MCS) and physical (PCS). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with higher scores indicating better health status. LS mean was determined by ANCOVA with factors for treatment and previous RA therapy population included as fixed factors,

Outcome measures

Outcome measures
Measure	Placebo n=21 Participants Participants received IV infusion of 0.9% sodium chloride solution (Placebo).	LY3462817 300 mg n=23 Participants Participants received IV infusion of 300 mg LY3462817 solution.	LY3462817 700 mg n=47 Participants Participants received IV infusion of 700 mg LY3462817 solution.
Change From Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute) MCS	3.48 Units on a scale Standard Error 1.715	0.55 Units on a scale Standard Error 1.630	4.64 Units on a scale Standard Error 1.166
Change From Baseline in Mental Component Score (MCS), Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute) PCS	5.01 Units on a scale Standard Error 1.711	7.03 Units on a scale Standard Error 1.633	6.43 Units on a scale Standard Error 1.165

SECONDARY outcome

Timeframe: Week 12

Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.

PK: Observed Concentration of LY3462817

Outcome measures

Outcome measures
Measure	Placebo n=25 Participants Participants received IV infusion of 0.9% sodium chloride solution (Placebo).	LY3462817 300 mg n=49 Participants Participants received IV infusion of 300 mg LY3462817 solution.	LY3462817 700 mg Participants received IV infusion of 700 mg LY3462817 solution.
Pharmacokinetics (PK): Observed Concentration of LY3462817	7970 nanograms per milliliter Interval 1290.0 to 17100.0	15600 nanograms per milliliter Interval 1820.0 to 36600.0	—

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

LY3462817 300 mg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

LY3462817 700 mg

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=24 participants at risk Participants received IV infusion of 0.9% sodium chloride solution (Placebo).	LY3462817 300 mg n=25 participants at risk Participants received IV infusion of 300 mg LY3462817 solution.	LY3462817 700 mg n=49 participants at risk Participants received IV infusion of 700 mg LY3462817 solution.
Endocrine disorders Hypothyroidism	0.00% 0/24 • Baseline, up to Week 12 All 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.	0.00% 0/25 • Baseline, up to Week 12 All 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.	2.0% 1/49 • Number of events 1 • Baseline, up to Week 12 All 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.

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60