A Study of LY3462817 in Participants With Rheumatoid Arth... | NCT04634253

ID	Type	Description	Link
J1A-MC-KDAD	Other Identifier	Eli Lilly and Company
2020-002673-10	EudraCT Number

Label	Type	Description	Intervention Names
LY3462817 300 mg	Experimental	Participants received Intravenous (IV) infusion of 300 mg LY3462817 solution.	Drug: LY3462817
LY3462817 700 mg	Experimental	Participants received IV infusion of 700 mg LY3462817 solution.	Drug: LY3462817
Placebo	Placebo Comparator	Participants received IV infusion of 0.9% sodium chloride solution (Placebo).	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Given IV	Placebo
LY3462817

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline on the Disease Activity Score Modified to Include the 28 Diarthrodial Joint Count-High-Sensitivity C-Reactive Protein (DAS28-hsCRP)	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 (=) 0.56square root (sqrt) (TJC28) plus (+) 0.28sqrt (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.	Baseline, Week 12

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants Achieving 20% Improvement in American College of Rheumatology Criteria (ACR20)	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).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Have a diagnosis of adult onset RA as defined by the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for at least 3 months prior to screening
Have moderately to severely active RA defined by the presence of ≥6 swollen joints (based on 66 joint count) and ≥6 tender joints (based on 68 joint count) at screening and baseline. The distal interphalangeal joint should be evaluated but not included in the total count to determine eligibility
Have at least 1 of the following:
- positive test results for rheumatoid factor or anti-citrullinated peptide antibodies at screening, OR
- previous radiographs documenting bony erosions in hands or feet consistent with RA
Have C-reactive protein (CRP) >1.2 times upper limit of normal (ULN) per the central laboratory at screening
Demonstrated an inadequate response to, or loss of response or intolerance to:
- at least 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD) treatment OR
- at least 1 biologic DMARD/tsDMARD treatment

Exclusion Criteria:

Class IV RA according to ACR revised response criteria
Have a diagnosis or history of malignant disease within 5 years prior to baseline, with the exceptions of:
- basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years, or
- cervical carcinoma in situ, with no evidence of recurrence within the 5 years prior to baseline
Have presence of confirmed cervical dysplasia
Have had various types of infection within 3 months of screening or develops any of these infections before the randomization visit.
Have any of the following:
- Human immunodeficiency virus (HIV) infection
- Current infection with hepatitis B virus (HBV) (i.e., positive for hepatitis B surface antigen and/or polymerase chain reaction (PCR) positive for HBV DNA
- Current infection with hepatitis C virus (HCV) (i.e., positive for HCV RNA)
- Active tuberculosis (TB)
Have failed more than 2 biologic DMARDs (bDMARDs) or tsDMARDs (e.g. excluded if have received 2 bDMARDs and 1 tsDMARD)

Name	Affiliation	Role
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 Director

Facility	Status	City	State	ZIP	Country	Contacts
Arizona Arthritis & Rheumatology Associates, P. C.		Mesa	Arizona	85210	United States
Arizona Arthritis & Rheumatology Associates, P. C.

PubMed Identifier	Type	Citation	Retractions
37494493	Derived	Tuttle J, Emery P, Nirula A. Phase 2 Trial of Peresolimab for Adults with Rheumatoid Arthritis. Reply. N Engl J Med. 2023 Jul 27;389(4):378-379. doi: 10.1056/NEJMc2307020. No abstract available.
37195941	Derived	Tuttle J, Drescher E, Simon-Campos JA, Emery P, Greenwald M, Kivitz A, Rha H, Yachi P, Kiley C, Nirula A. A Phase 2 Trial of Peresolimab for Adults with Rheumatoid Arthritis. N Engl J Med. 2023 May 18;388(20):1853-1862. doi: 10.1056/NEJMoa2209856.

Label	URL
A Study of LY3462817 in Participants With Rheumatoid Arthritis	View source

ID	Title	Description
FG000	Placebo	Participants received intravenous (IV) infusion of 0.9% sodium chloride solution (Placebo).
FG001	LY3462817 300 mg	Participants received IV infusion of 300 milligrams (mg) LY3462817 solution.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 11, 2020	Jan 2, 2023

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline on the Disease Activity Score Modified to Include the 28 Diarthrodial Joint Count-High-Sensitivity C-Reactive Protein (DAS28-hsCRP)

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.

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

Posted

Least Squares Mean

Standard Error

Units on a scale

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Participants received IV infusion of 0.9% sodium chloride solution (Placebo).
OG001	LY3462817 300 mg	Participants received IV infusion of 300 mg LY3462817 solution.
OG002	LY3462817 700 mg	Participants received IV infusion of 700 mg LY3462817 solution.

Units	Counts
Participants	OG00020 OG00122 OG00242

Title

Denominators

Categories

Title	Measurements
	OG000-0.99± 0.261 OG001-1.88± 0.249 OG002-2.09± 0.184

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis		0.017		LS Mean	-0.88	Standard Error of the Mean	0.361	2-Sided	95	-1.60	-0.16					Superiority
OG000 OG002		Mixed Models Analysis		<0.001

Secondary

Percentage of Participants Achieving 20% Improvement in American College of Rheumatology Criteria (ACR20)

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).

All randomized participants.

Posted

Number

95% Confidence Interval

Percentage of Participants

Week 12

ID	Title	Description
OG000	Placebo	Participants received IV infusion of 0.9% sodium chloride solution (Placebo).
OG001	LY3462817 300 mg	Participants received IV infusion of 300 mg LY3462817 solution.
OG002	LY3462817 700 mg	Participants received IV infusion of 700 mg LY3462817 solution.

Secondary

Percentage of Participants Achieving 70% Improvement in American College of Rheumatology Criteria (ACR70)

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).

All randomized participants.

Posted

Number

95% Confidence Interval

Percentage of Participants

Week 12

ID	Title	Description
OG000	Placebo	Participants received IV infusion of 0.9% sodium chloride solution (Placebo).
OG001	LY3462817 300 mg	Participants received IV infusion of 300 mg LY3462817 solution.
OG002	LY3462817 700 mg	Participants received IV infusion of 700 mg LY3462817 solution.

Secondary

Percentage of Participants Achieving 50% Improvement in American College of Rheumatology Criteria (ACR50)

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).

All randomized participants.

Posted

Number

95% Confidence Interval

Percentage of Participants

Week 12

ID	Title	Description
OG000	Placebo	Participants received IV infusion of 0.9% sodium chloride solution (Placebo).
OG001	LY3462817 300 mg	Participants received IV infusion of 300 mg LY3462817 solution.
OG002	LY3462817 700 mg	Participants received IV infusion of 700 mg LY3462817 solution.

Secondary

Change From Baseline for Mean Simplified Disease Activity Index (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.

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

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Participants received IV infusion of 0.9% sodium chloride solution (Placebo).
OG001	LY3462817 300 mg	Participants received IV infusion of 300 mg LY3462817 solution.
OG002	LY3462817 700 mg

Secondary

Change From Baseline for Mean Clinical Disease Activity Index (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.

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

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Participants received IV infusion of 0.9% sodium chloride solution (Placebo).
OG001	LY3462817 300 mg	Participants received IV infusion of 300 mg LY3462817 solution.

Secondary

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)

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,

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

Posted

Least Squares Mean

Standard Error

Units on a scale

Baseline, Week 12

ID	Title	Description
OG000	Placebo	Participants received IV infusion of 0.9% sodium chloride solution (Placebo).
OG001	LY3462817 300 mg	Participants received IV infusion of 300 mg LY3462817 solution.

Secondary

Pharmacokinetics (PK): Observed Concentration of LY3462817

PK: Observed Concentration of LY3462817

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

Posted

Median

95% Confidence Interval

nanograms per milliliter

Week 12

ID	Title	Description
OG000	LY3462817 300 mg	Participants received IV infusion of 300 mg LY3462817 solution.
OG001	LY3462817 700 mg	Participants received IV infusion of 700 mg LY3462817 solution.

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0010 events0 affected25 at risk EG0021 events1 affected49 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0010 events0 affected25 at risk EG0024 events4 affected49 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0010 events0 affected25 at risk EG0021 events1 affected49 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected25 at risk EG0020 events0 affected49 at risk
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0010 events0 affected25 at risk EG0021 events1 affected49 at risk
Covid-19	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0011 events1 affected25 at risk EG0021 events1 affected49 at risk
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0011 events1 affected25 at risk EG0020 events0 affected49 at risk
Helicobacter infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0011 events1 affected25 at risk EG0020 events0 affected49 at risk
Herpes simplex	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected25 at risk EG0020 events0 affected49 at risk
Mastitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0011 events1 affected25 at risk EG0020 events0 affected49 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected24 at risk EG0012 events2 affected25 at risk EG0021 events1 affected49 at risk
Rhinitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0010 events0 affected25 at risk EG0021 events1 affected49 at risk
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0011 events1 affected25 at risk EG0020 events0 affected49 at risk
Skin bacterial infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0011 events1 affected25 at risk EG0020 events0 affected49 at risk
Tooth abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected25 at risk EG0020 events0 affected49 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0010 events0 affected25 at risk EG0021 events1 affected49 at risk
Upper respiratory tract infection bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0010 events0 affected25 at risk EG0021 events1 affected49 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0010 events0 affected25 at risk EG0021 events1 affected49 at risk
Vulvovaginal candidiasis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 events0 affected19 at risk EG0010 events0 affected20 at risk EG0021 events1 affected43 at risk
Weight increased	Investigations	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0011 events1 affected25 at risk EG0020 events0 affected49 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0010 events0 affected25 at risk EG0021 events1 affected49 at risk
Dyslipidaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0002 events2 affected24 at risk EG0010 events0 affected25 at risk EG0021 events1 affected49 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0010 events0 affected25 at risk EG0021 events1 affected49 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0010 events0 affected25 at risk EG0021 events1 affected49 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0010 events0 affected25 at risk EG0021 events1 affected49 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0010 events0 affected25 at risk EG0021 events1 affected49 at risk
Rheumatoid arthritis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected25 at risk EG0020 events0 affected49 at risk
B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected25 at risk EG0020 events0 affected49 at risk
Allodynia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0011 events1 affected25 at risk EG0020 events0 affected49 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0011 events1 affected25 at risk EG0020 events0 affected49 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0010 events0 affected25 at risk EG0021 events1 affected49 at risk
Hypoaesthesia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0010 events0 affected25 at risk EG0021 events1 affected49 at risk
Dermatitis atopic	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected24 at risk EG0010 events0 affected25 at risk EG0021 events1 affected49 at risk
Onychoclasis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected25 at risk EG0020 events0 affected49 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected25 at risk EG0023 events1 affected49 at risk
Tooth extraction	Surgical and medical procedures	MedDRA	Systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected25 at risk EG0020 events0 affected49 at risk
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0002 events2 affected24 at risk EG0010 events0 affected25 at risk EG0020 events0 affected49 at risk

ID	Term
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Title	Description
BG000	Placebo	Participants received IV infusion of 0.9% sodium chloride solution (Placebo).
BG001	LY3462817 300 mg	Participants received IV infusion of 300 mg LY3462817 solution.
BG002	LY3462817 700 mg	Participants received IV infusion of 700 mg LY3462817 solution.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received IV infusion of 0.9% sodium chloride solution (Placebo).	24	0	24	9	24
EG001	LY3462817 300 mg	Participants received IV infusion of 300 mg LY3462817 solution.	25	0	25	8	25
EG002	LY3462817 700 mg	Participants received IV infusion of 700 mg LY3462817 solution.	49	1	49	13	49