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LY2127399

Phase 3

Rheumatoid Arthritis | Small molecule | Immunology |Eli Lilly and Company|Last Updated: Mar 1, 2019

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDDMCBiomarker
Total Trials5
Total Enrollment1,402
FDA Designations
No designations recorded
Clinical Trials (5)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01202760A Rheumatoid Arthritis Study in ParticipantsPHASE3 COMPLETED 1,004Jan 1, 2011Jul 1, 2013Apr 25, 2018213 United States, Argentina +20
NCT00837811An Open Label Extension Study in Participants With Rheumatoid ArthritisPHASE2 COMPLETED 182Feb 1, 2009Jan 1, 2012Apr 25, 201862 United States, Australia +12
NCT00785928A Study for Patients With Active Rheumatoid Arthritis Despite Ongoing Methotrexate TherapyPHASE2 COMPLETED 158Oct 1, 2008Dec 1, 2010Jul 10, 201848 United States, Argentina +10
NCT01253291A Study of Japanese Rheumatoid Arthritis ParticipantsPHASE1 COMPLETED 26May 1, 2010Mar 1, 2014Mar 1, 20199 Japan
NCT01253226A Study for Japanese Participants With Rheumatoid Arthritis (RA)PHASE1 COMPLETED 32Sep 1, 2009Aug 1, 2011Oct 23, 201810 Japan
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Study Endpoints
Primary Endpoints
Percentage of Participants With American College of Rheumatology 20% (ACR20) Response
Up to 24 weeks

ACR20 Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis. ACR20 Responder: had \>=20% improvement from baseline in both 68 tender and 66 swollen joint counts and \>=20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). Percentage of participants achieving ACR20 response=(number of ACR20 responders/number of participants treated)\*100. All non-responders at Week 16 as well as all participants who discontinued study treatment at any time, for any reason, were defined as non-responders starting at that timepoint and going forward, including Week 24 endpoint.

Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Baseline through Week 52 (up to 48 weeks of treatment or ED and follow-up through Week 52)

A TEAE started on or after the date and time of the first dose of study drug administered in this study, or started prior to the study drug administration but worsened after the study drug started. Clinically significant events were defined as SAEs and other non-serious adverse events (AEs). A summary of SAEs and other non-serious AEs is located in the Reported Adverse Events module. Participants were on treatment up to 48 weeks. If a participant completed 48 weeks of treatment, the post-study treatment follow-up started at the next visit, 4 weeks later (Week 52). If a participant discontinued treatment early \[early discontinuation (ED)\], the post-study treatment follow-up started immediately afterwards. Baseline was defined as Week 0 in this study \[which is equivalent to Week 24 of the participant's prior study: Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928)\].

Number of Participants With Planned Laboratory Evaluations (Including Hematology, Clinical Chemistry, and Urinalysis) Reported as AEs
Baseline through Week 112

For each planned laboratory evaluation, the range of values to be reported as AEs, regardless of causality, was pre-specified. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. Baseline was defined as Week 0 in this study \[which is equivalent to Week 24 of the participant's prior study: Study H9B-MC-BCDG (NCT00689728) or Study H9B-MC-BCDH (NCT00785928)\].

Percentage of Participants Who Achieved American College of Rheumatology (ACR) 50 Response up to 24 Weeks
Up to week 24

ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. An ACR50 Responder is defined as a participant with \>50% improvement from baseline in both tender and swollen joint counts and in at least 3 of the following 5 criteria: physician global assessment, participant global assessment, functional ability measure (Health Assessment Questionnaire-Disability Index which measures participants' perceived degree of difficulty when performing various daily activities), visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Baseline up to 72 weeks

Included are the number of participants who experienced SAEs and treatment-emergent other non-SAEs. A summary of SAEs and other non-SAEs, regardless of causality, is located in the Reported Adverse Events (AEs) module.

Number of Participants With Adverse Events (AEs) [Clinically Significant Effects]
Baseline through study completion (up to Week 32 plus up to 12 weeks for B cell monitoring)

Clinically significant effects are defined as serious AEs (SAEs) and other non-serious AEs regardless of causality. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

Secondary Endpoints
Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Responses
Up to 24 weeks
Mean Percent Improvement in American College of Rheumatology Percent Improvement (ACR-N)
Up to 24 weeks
Change From Baseline to 24 Weeks in Tender Joint Count (68 Joint Count)
Baseline, up to 24 weeks
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Study Design & Arms
AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
120 mg LY2127399EXPERIMENTALLY2127399: 120 milligrams (mg), subcutaneous (SC) injection, every 4 weeks for 24 weeks. Participants received a 240-mg (2 SC injections of 120 mg each) loading dose of LY2127399 when initiating treatment. During the Treatment Period, for blinding purposes, participants alternated injections of LY2127399 and injections of Placebo every 2 weeks. After 16 weeks, non-responders received 90 mg of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.
90 mg LY2127399EXPERIMENTALLY2127399: 90 milligrams (mg), subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a 180-mg (2 SC injections of 90 mg each) loading dose of LY2127399 when initiating treatment. After 16 weeks, non-responders continued to receive 90 mg of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.
PlaceboPLACEBO_COMPARATORPlacebo: subcutaneous (SC) injection, every 2 weeks for 24 weeks. Participants received a loading dose of 2 SC injections of Placebo when initiating treatment. After 16 weeks, non-responders received 90 milligrams (mg) of LY2127399 every 2 weeks for the rest of the 24-week Treatment Period.
LY2127399EXPERIMENTAL -
1 mg LY2127399EXPERIMENTAL -
3 mg LY2127399EXPERIMENTAL -
10 mg LY2127399EXPERIMENTAL -
30 mg LY2127399EXPERIMENTAL -
60 mg LY2127399EXPERIMENTAL -
30mg/120 mg LY2127399EXPERIMENTALParticipants in the 30 milligrams (mg) every 4 weeks arm of the lead-in study will receive 30 mg every 4 weeks until the safety of the 120 mg every 4 weeks dose is confirmed in the lead-in study.
30 milligrams (mg) TabalumabEXPERIMENTAL30 mg tabalumab every 4 weeks (Q4W) for 20 weeks (6 doses of study drug)
60 mg TabalumabEXPERIMENTAL60 mg tabalumab Q4W for 20 weeks (6 doses of study drug)
120 mg TabalumabEXPERIMENTAL120 mg tabalumab Q4W for 20 weeks (6 doses of study drug)
Placebo Q4WPLACEBO_COMPARATORQ4W for 20 weeks
120 mg once every 2 weeks (Q2W) TabalumabEXPERIMENTALInitial loading dose of 240 mg tabalumab followed by 120 mg Q2W for 20 weeks (10 doses of study drug)
Placebo Q2WPLACEBO_COMPARATORQ2W for 20 weeks
Interventions
NameTypeDescription
LY2127399DRUG -
PlaceboDRUG -
LY2127399 (Tabalumab)DRUGAdministered subcutaneously
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites213

Inclusion Criteria: * Diagnosis of Rheumatoid Arthritis (RA) of more than 6 months and less than 15 years * Global Assessment of Disease Activity visual analog scale (VAS) greater than or equal to 20/100 millimeters (mm) * If on one or more conventional disease-modifying anti-rheumatic Drugs (DMARD...

Countries:United StatesArgentinaAustraliaBulgariaColombiaCroatiaHungaryIndiaJapanLithuaniaMalaysiaMexicoNew ZealandPolandRomaniaRussiaSlovakiaSouth AfricaSouth KoreaSri LankaTaiwanUkraineAustriaBelgiumBrazilCanadaChileGermanyPuerto Rico
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