Back to resultsA Study of LY3462817 in Participants With Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
LY3462817
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
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)
Sites / Locations
- Arizona Arthritis & Rheumatology Associates, P. C.
- Arizona Arthritis & Rheumatology Associates, P. C.
- Desert Medical Advances
- Inland Rheumatology & Osteoporosis Medical Group
- Physician Research Collaboration, LLC
- Health Research of Oklahoma
- Altoona Center For Clinical Research
- Medical Plus
- PV Medical Services s.r.o.
- CRU Hungary Kft.
- Revita Clinic
- Vital Medical Center
- Budai Irgalmasrendi Korhaz
- Clinexpert Egeszsegugyi Szolgaltato es Kereskedelmi Kft.
- Centro Medico del Angel
- RM Pharma Specialists S.A. de C.V.
- Centro de Estudios de Investigacion Basica y Clinica, S.C.
- Köhler & Milstein Research
- Investigacion y Biomedicina de Chihuahua
- Klinika Reumatologii i Ukladowych Chorob Tkanki Lacznej
- Twoja Przychodnia Centrum Medyczne Nowa Sol
- Reumatika - Centrum Reumatologii
- Nzoz Bif-Med
- Centro Reumatologico Caguas
- Latin Clinical Trial Center
- Royal Free Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
LY3462817 300 mg
LY3462817 700 mg
Placebo
Arm Description
Participants received Intravenous (IV) infusion of 300 mg LY3462817 solution.
Participants received IV infusion of 700 mg LY3462817 solution.
Participants received IV infusion of 0.9% sodium chloride solution (Placebo).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
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).
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).
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.
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.
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,
Pharmacokinetics (PK): Observed Concentration of LY3462817
PK: Observed Concentration of LY3462817
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04634253
Brief Title
A Study of LY3462817 in Participants With Rheumatoid Arthritis
Official Title
A Phase 2 Study to Evaluate the Efficacy and Safety of LY3462817 in Participants With Moderately to Severely Active Rheumatoid Arthritis
Study Type
Interventional
2. Study Status
Record Verification Date
June 1, 2023
Overall Recruitment Status
Completed
Study Start Date
January 4, 2021 (Actual)
Primary Completion Date
January 10, 2022 (Actual)
Study Completion Date
June 29, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The reason for this study is to see if the study drug LY3462817 is safe and effective in participants with moderately to severely active rheumatoid arthritis (RA).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
98 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LY3462817 300 mg
Arm Type
Experimental
Arm Description
Participants received Intravenous (IV) infusion of 300 mg LY3462817 solution.
Arm Title
LY3462817 700 mg
Arm Type
Experimental
Arm Description
Participants received IV infusion of 700 mg LY3462817 solution.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received IV infusion of 0.9% sodium chloride solution (Placebo).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
LY3462817
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Change From Baseline on the Disease Activity Score Modified to Include the 28 Diarthrodial Joint Count-High-Sensitivity C-Reactive Protein (DAS28-hsCRP)
Description
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.
Time Frame
Baseline, Week 12
Secondary Outcome Measure Information:
Title
Percentage of Participants Achieving 20% Improvement in American College of Rheumatology Criteria (ACR20)
Description
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).
Time Frame
Week 12
Title
Percentage of Participants Achieving 70% Improvement in American College of Rheumatology Criteria (ACR70)
Description
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).
Time Frame
Week 12
Title
Percentage of Participants Achieving 50% Improvement in American College of Rheumatology Criteria (ACR50)
Description
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).
Time Frame
Week 12
Title
Change From Baseline for Mean Simplified Disease Activity Index (SDAI)
Description
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.
Time Frame
Baseline, Week 12
Title
Change From Baseline for Mean Clinical Disease Activity Index (CDAI)
Description
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.
Time Frame
Baseline, Week 12
Title
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)
Description
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,
Time Frame
Baseline, Week 12
Title
Pharmacokinetics (PK): Observed Concentration of LY3462817
Description
PK: Observed Concentration of LY3462817
Time Frame
Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
Arizona Arthritis & Rheumatology Associates, P. C.
City
Mesa
State/Province
Arizona
ZIP/Postal Code
85210
Country
United States
Facility Name
Arizona Arthritis & Rheumatology Associates, P. C.
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85037
Country
United States
Facility Name
Desert Medical Advances
City
Palm Desert
State/Province
California
ZIP/Postal Code
92260
Country
United States
Facility Name
Inland Rheumatology & Osteoporosis Medical Group
City
Upland
State/Province
California
ZIP/Postal Code
91786
Country
United States
Facility Name
Physician Research Collaboration, LLC
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68516
Country
United States
Facility Name
Health Research of Oklahoma
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73103
Country
United States
Facility Name
Altoona Center For Clinical Research
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
Facility Name
Medical Plus
City
Uherske Hradiste
State/Province
Zlínský Kraj
ZIP/Postal Code
686 01
Country
Czechia
Facility Name
PV Medical Services s.r.o.
City
Zlin
ZIP/Postal Code
760 01
Country
Czechia
Facility Name
CRU Hungary Kft.
City
Miskolc
State/Province
Borsod-Abaúj-Zemplén
ZIP/Postal Code
3529
Country
Hungary
Facility Name
Revita Clinic
City
Budapest
State/Province
Pest
ZIP/Postal Code
1027
Country
Hungary
Facility Name
Vital Medical Center
City
Veszprem
State/Province
Veszprém City
ZIP/Postal Code
8200
Country
Hungary
Facility Name
Budai Irgalmasrendi Korhaz
City
Budapest
ZIP/Postal Code
1027
Country
Hungary
Facility Name
Clinexpert Egeszsegugyi Szolgaltato es Kereskedelmi Kft.
City
Budapest
ZIP/Postal Code
1033
Country
Hungary
Facility Name
Centro Medico del Angel
City
Mexicali
State/Province
Baja California
ZIP/Postal Code
21100
Country
Mexico
Facility Name
RM Pharma Specialists S.A. de C.V.
City
Mexico City
State/Province
Distrito Federal
ZIP/Postal Code
03100
Country
Mexico
Facility Name
Centro de Estudios de Investigacion Basica y Clinica, S.C.
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
44690
Country
Mexico
Facility Name
Köhler & Milstein Research
City
Mérida
State/Province
Yucatan
ZIP/Postal Code
97070
Country
Mexico
Facility Name
Investigacion y Biomedicina de Chihuahua
City
Chihuahua
ZIP/Postal Code
31000
Country
Mexico
Facility Name
Klinika Reumatologii i Ukladowych Chorob Tkanki Lacznej
City
Bydgoszcz
State/Province
Kujawsko-pomorskie
ZIP/Postal Code
85-168
Country
Poland
Facility Name
Twoja Przychodnia Centrum Medyczne Nowa Sol
City
Nowa Sol
State/Province
Lubuskie
ZIP/Postal Code
67-100
Country
Poland
Facility Name
Reumatika - Centrum Reumatologii
City
Warszawa
State/Province
Mazowieckie
ZIP/Postal Code
02-691
Country
Poland
Facility Name
Nzoz Bif-Med
City
Bytom
State/Province
Śląskie
ZIP/Postal Code
41-902
Country
Poland
Facility Name
Centro Reumatologico Caguas
City
Caguas
ZIP/Postal Code
00725
Country
Puerto Rico
Facility Name
Latin Clinical Trial Center
City
San Juan
ZIP/Postal Code
909
Country
Puerto Rico
Facility Name
Royal Free Hospital
City
Barnet
ZIP/Postal Code
EN53DJ
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement
IPD Sharing Time Frame
Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting
IPD Sharing Access Criteria
Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting
IPD Sharing URL
http://vivli.org/
Links:
URL
https://trials.lillytrialguide.com/en-US/trial/5XEBVhZJQJiPOegLRVANvY
Description
A Study of LY3462817 in Participants With Rheumatoid Arthritis
Learn more about this trial
A Study of LY3462817 in Participants With Rheumatoid Arthritis
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