A Study of Japanese Rheumatoid Arthritis Participants

An Open-Label Extension Study of Multiple Subcutaneous Doses of LY2127399 in Japanese Patients With Rheumatoid Arthritis Treated With Methotrexate

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01253291

Enrollment

Registered

2010-12-03

Start date

2010-05-31

Completion date

2014-03-31

Last updated

2019-03-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rheumatoid Arthritis

Brief summary

The objective of this study is to evaluate the safety and tolerability of 48 weeks subcutaneous (SC) dosing with LY2127399 for participants who have participated in a prior LY2127399 clinical study. At the end of the 48-week treatment period, participants will participate in a 24-week follow-up period. Additional follow up after Week 72 may continue to assess B-cell recovery.

Interventions

DRUGLY2127399

Administered subcutaneously every 4 weeks for 48 weeks

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

20 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Have given written informed consent * Women must not be pregnant, breastfeeding or be at risk to become pregnant during study participation * Must have completed treatment and 12 week follow up period in prior LY2127399 study NCT01253226 \[Study H9B-JE-BCDK (BCDK)\]

Exclusion criteria

* Have had any safety event during the previous LY2127399 (BCDK) study that participants participated in * Have received, during previous study (BCDK), any drugs prohibited in the study protocol which includes unapproved drugs, live vaccines, or any biologic or non-biologic disease-modifying anti-rheumatic drug (DMARD) except for, methotrexate (MTX), hydroxychloroquine, sulfasalazine or bucillamine

Design outcomes

Primary

Measure	Time frame	Description
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.

Secondary

Measure	Time frame	Description
Percent Change From Baseline in Rheumatoid Factor (RF)	Baseline and Weeks 12, 24, 36, 52, and 72	RF is a disease-related, peripheral blood biomarker used to assess disease progression of RA. A reduction in RF values indicate an improvement in RA symptoms.
Percent Change From Baseline in Immunoglobulins [Immunoglobulin (Ig) G, IgM, and IgA]	Baseline and Weeks 12, 24, 36, 52, and 72	IgG, IgM and IgA are disease related peripheral blood biomarkers used to assess disease progression of RA. A reduction in Ig values indicate an improvement in RA symptoms.
Percent Change From Baseline in CD20+ B-cell Count	Baseline and Weeks 12, 24, 36, 52, and 72	CD20+ B-cells are a disease-related peripheral blood biomarker used to assess disease progression of RA. A reduction in CD20+ B-cell values indicate an improvement in RA symptoms.
Percent Change From Baseline in Anti-Cyclic Citrullinated Peptide (Anti-CCP) Antibody	Baseline and Weeks 12, 24, 36, 52, and 72	Anti-CCP is a disease related peripheral blood biomarker used to assess disease progression of rheumatoid arthritis (RA). A reduction in anti-CCP values indicates an improvement.
Percent Change From Baseline in C-Reactive Protein (CRP)	Baseline and Weeks 12, 24, 36, 52, and 72	CRP is a disease-related peripheral blood biomarker used to assess disease progression of RA. A reduction in CRP values indicate an improvement in RA symptoms.
Percent Change From Baseline in Erythrocyte Sedimentation Rate (ESR)	Baseline and Weeks 12, 24, 36, 52, and 72	ESR is a disease related peripheral blood biomarker used to assess, in part, the effect of LY2127399 on the participants' RA disease progression. A reduction in ESR values indicate an improvement in RA symptoms.
Percent Change From Baseline in Peripheral B-cell Subsets	Baseline and Weeks 12, 24, 36, 52, and 72	Peripheral B cell subsets (Mature Naive B-cells and Switched Memory B cells) are disease-related peripheral blood biomarkers used to assess disease progression of RA. A reduction in cell values indicate an improvement in RA symptoms.

Countries

Japan

Participant flow

Pre-assignment details

Participants who completed NCT01253226 \[Study H9B-JE-BCDK (BCDK)\] were enrolled into open-label study NCT01253291 \[H9B-JE-BCDL (BCDL\]).

Participants by arm

Arm	Count
Placebo/LY2127399 120 mg Q4W Participants who previously received placebo in Study BCDK were assigned to receive 120 mg of LY2127399 administered SC Q4W for 48 weeks.	6
LY2127399 30 mg Q4W/120 mg Q4W Participants who previously received 30 mg of LY2127399 Q4W in Study BCDK were assigned to receive 120 mg of LY2127399 administered SC Q4W for 48 weeks.	6
LY2127399 60 mg Q4W/120 mg Q4W Participants who previously received 60 mg of LY2127399 Q4W in Study BCDK were assigned to receive 120 mg of LY2127399 administered SC Q4W for 48 weeks.	4
LY2127399 120 mg Q4W/120 mg Q4W Participants who previously received 120 mg of LY2127399 Q4W in Study BCDK were assigned to receive 120 mg of LY2127399 administered SC Q4W for 48 weeks.	5
LY2127399 120 mg Q2W/120 mg Q4W Participants who previously received 120 mg of LY2127399 Q2W in Study BCDK were assigned to receive 120 mg of LY2127399 administered SC Q4W for 48 weeks.	5
Total	26

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG004
Overall Study	Adverse Event	0	1	0
Overall Study	Lack of Efficacy	1	0	0
Overall Study	Physician Decision	2	0	2
Overall Study	Withdrawal by Subject	1	1	0

Baseline characteristics

Characteristic	Placebo/LY2127399 120 mg Q4W	LY2127399 30 mg Q4W/120 mg Q4W	LY2127399 60 mg Q4W/120 mg Q4W	LY2127399 120 mg Q4W/120 mg Q4W	LY2127399 120 mg Q2W/120 mg Q4W	Total
Age, Continuous	54.7 years STANDARD_DEVIATION 17.4	66.5 years STANDARD_DEVIATION 5.7	47.8 years STANDARD_DEVIATION 16.9	53.8 years STANDARD_DEVIATION 14.1	55.8 years STANDARD_DEVIATION 8.6	56.4 years STANDARD_DEVIATION 13.5
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants	6 Participants	4 Participants	5 Participants	5 Participants	26 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian	6 Participants	6 Participants	4 Participants	5 Participants	5 Participants	26 Participants
Region of Enrollment Japan	6 Participants	6 Participants	4 Participants	5 Participants	5 Participants	26 Participants
Sex: Female, Male Female	5 Participants	6 Participants	2 Participants	3 Participants	4 Participants	20 Participants
Sex: Female, Male Male	1 Participants	0 Participants	2 Participants	2 Participants	1 Participants	6 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	5 / 6	4 / 6	4 / 4	3 / 5	4 / 5
serious Total, serious adverse events	1 / 6	0 / 6	0 / 4	0 / 5	0 / 5

Outcome results

Primary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

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.

Time frame: Baseline up to 72 weeks

Population: All enrolled participants who received at least 1 dose of study drug during BCDL.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo/LY2127399 120 mg Q4W	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	SAEs	0 Participants
Placebo/LY2127399 120 mg Q4W	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Treatment Emergent Other Non-Serious AEs	5 Participants
LY2127399 30 mg Q4W/120 mg Q4W	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	SAEs	0 Participants
LY2127399 30 mg Q4W/120 mg Q4W	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Treatment Emergent Other Non-Serious AEs	4 Participants
LY2127399 60 mg Q4W/120 mg Q4W	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	SAEs	0 Participants
LY2127399 60 mg Q4W/120 mg Q4W	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Treatment Emergent Other Non-Serious AEs	4 Participants
LY2127399 120 mg Q4W/120 mg Q4W	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Treatment Emergent Other Non-Serious AEs	3 Participants
LY2127399 120 mg Q4W/120 mg Q4W	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	SAEs	0 Participants
LY2127399 120 mg Q2W/120 mg Q4W	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	SAEs	0 Participants
LY2127399 120 mg Q2W/120 mg Q4W	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Treatment Emergent Other Non-Serious AEs	4 Participants

Secondary

Percent Change From Baseline in Anti-Cyclic Citrullinated Peptide (Anti-CCP) Antibody

Anti-CCP is a disease related peripheral blood biomarker used to assess disease progression of rheumatoid arthritis (RA). A reduction in anti-CCP values indicates an improvement.