Study of LX3305 in Subjects With Active Rheumatoid Arthritis on Stable Methotrexate

A Phase 2, Multi-center, Randomized, Double Blind, Placebo-controlled, Multiple-dose Study to Determine the Safety and Efficacy of Daily Orally Administered LX3305 in Subjects With Active Rheumatoid Arthritis (RA) on Stable Methotrexate (MTX) Therapy

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00903383

Enrollment

208

Registered

2009-05-18

Start date

2009-07-31

Completion date

Unknown

Last updated

2011-12-15

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 purpose of the study is to evaluate the safety, tolerability, and effectiveness of LX3305 versus a placebo control in subjects with active rheumatoid arthritis on stable methotrexate therapy.

Interventions

DRUGLX3305 low dose

A low dose of LX3305; daily oral intake for 12 weeks

DRUGLX3305 mid dose

A mid dose of LX3305; daily oral intake for 12 weeks

DRUGLX3305 high dose

A high dose of LX3305; daily oral intake for 12 weeks

DRUGPlacebo

Matching placebo dosing with daily oral intake for 12 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Males and females aged 18-75 years old * Rheumatoid arthritis present for at least 6 months, functional class I, II, or III as defined by ACR criteria * Active disease as determined by the presence of ≥6 swollen joints, ≥6 tender joints, and serum C-reactive protein level \> upper limit of normal * Receiving stable dose of MTX (≥10 mg/wk) and folate supplementation at least 8 weeks prior to Day 1 * Ability to provide written informed consent

Exclusion criteria

* RA diagnosis prior to 16 years of age (Juvenile RA) * Lack of response to \>3 disease modifying anti-rheumatic drugs (DMARDs) or exposure to \>1 biologic DMARD * Use of DMARDs other than MTX within 12 weeks prior to Day 1 * Intra-articular and/or parenteral corticosteroids within 4 weeks prior to study Day 1 * Blood donation or receipt of live vaccine within 4 weeks prior to Day 1 * Major surgical procedure within 8 weeks prior to Day 1 * Any systemic inflammatory condition, recurrent infection, or current infection other than onychomycosis * History of cancer within 5 years prior to Day 1 * Presence of hepatic or biliary disease * History of tuberculosis * History of human immunodeficiency virus (HIV)

Design outcomes

Primary

Measure	Time frame	Description
ACR20 Response at Week 12	Baseline and 12 weeks	Evaluates the efficacy of LX3305 by utilizing the American College of Rheumatology 20% response criteria (ACR20) at 12 weeks in subjects with active RA also receiving stable doses of MTX. For a response of ACR20, there had to be ≥20% improvement in swollen joint count, ≥20% improvement in painful/tender joint count, and ≥20% improvement in at least 3 of the following: subject's assessment of pain, global assessment of disease activity, assessment of physical function, or acute phase reactant (C-reactive protein or erythrocyte sedimentation rate).

Secondary

Measure	Time frame	Description
ACR50 Response at Week 12	Baseline and 12 weeks	Evaluates the efficacy of LX3305 by utilizing the American College of Rheumatology 50% response criteria (ACR50) at 12 weeks in subjects with active RA also receiving stable doses of MTX. For a response of ACR50, there had to be ≥50% improvement in swollen joint count, ≥50% improvement in painful/tender joint count, and ≥50% improvement in at least 3 of the following: subject's assessment of pain, global assessment of disease activity, assessment of physical function, or acute phase reactant (C-reactive protein or erythrocyte sedimentation rate).
ACR70 Response at Week 12	Baseline and 12 weeks	Evaluates the efficacy of LX3305 by utilizing the American College of Rheumatology 70% response criteria (ACR70) at 12 weeks in subjects with active RA also receiving stable doses of MTX. For a response of ACR70, there had to be ≥70% improvement in swollen joint count, ≥70% improvement in painful/tender joint count, and ≥70% improvement in at least 3 of the following: subject's assessment of pain, global assessment of disease activity, assessment of physical function, or acute phase reactant (C-reactive protein or erythrocyte sedimentation rate).
Hybrid ACR Response at Week 12	Baseline and 12 weeks	Evaluates the improvement in active RA by combining elements of the ACR20/50/70 with a continuous score of the mean change in core set measures. The percentage improvement from baseline was computed in each of the components of the ACR. The average percent improvement was calculated and used with the subject's ACR20, ACR50, and ACR70 status to compute the hybrid ACR response, with a positive change indicating improvement.
Change From Baseline in C-reactive Protein (mg/L) at Week 12	Baseline and 12 weeks	The C-reactive protein value (mg/L) at baseline was subtracted from the value for each of the treatment groups at Week 12.
Change From Baseline in Erythrocyte Sedimentation Rate (mm) at Week 12	Baseline and 12 weeks	The value for Erythrocyte Sedimentation Rate (mm) at baseline was subtracted from the value for each of the treatment groups at Week 12.

Countries

Bulgaria, Czechia, Hungary, Poland, Serbia, United States

Participant flow

Recruitment details

There were 43 study centers in 6 countries (10 in the US, 8 in Bulgaria, 4 in Czech Republic, 7 in Hungary, 11 in Poland, and 3 in Serbia). The first subject was enrolled on 31 August 2009, and the last subject completed the study on 30 September 2010.

Pre-assignment details

There was a 4 week screening period prior to the 12-week treatment period.

Participants by arm

Arm	Count
Low Dose A low dose of LX3305; daily oral intake for 12 weeks	55
Mid Dose A mid dose of LX3305; daily oral intake for 12 weeks	54
High Dose A high dose of LX3305; daily oral intake for 12 weeks	50
Placebo Matching placebo dosing with daily oral intake for 12 weeks	49
Total	208

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Adverse Event	1	2	3	1
Overall Study	Decision of Sponsor	1	0	0	0
Overall Study	Lost to Follow-up	0	0	0	1
Overall Study	Patient Decision	0	0	0	1
Overall Study	Patient Decision - Lack of Efficacy	0	1	0	0
Overall Study	Physician Decision	1	2	0	0
Overall Study	Withdrawal by Subject	4	1	0	2

Baseline characteristics

Characteristic	Low Dose	Mid Dose	High Dose	Placebo	Total
Age Continuous	56.5 years STANDARD_DEVIATION 9.25	55.8 years STANDARD_DEVIATION 9.2	56.4 years STANDARD_DEVIATION 10.89	57.5 years STANDARD_DEVIATION 10.19	56.5 years STANDARD_DEVIATION 9.83
Sex: Female, Male Female	47 Participants	43 Participants	37 Participants	41 Participants	168 Participants
Sex: Female, Male Male	8 Participants	11 Participants	13 Participants	8 Participants	40 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	10 / 55	5 / 54	10 / 50	12 / 49
serious Total, serious adverse events	2 / 55	0 / 54	0 / 50	0 / 49

Outcome results

Primary

ACR20 Response at Week 12

Evaluates the efficacy of LX3305 by utilizing the American College of Rheumatology 20% response criteria (ACR20) at 12 weeks in subjects with active RA also receiving stable doses of MTX. For a response of ACR20, there had to be ≥20% improvement in swollen joint count, ≥20% improvement in painful/tender joint count, and ≥20% improvement in at least 3 of the following: subject's assessment of pain, global assessment of disease activity, assessment of physical function, or acute phase reactant (C-reactive protein or erythrocyte sedimentation rate).

Time frame: Baseline and 12 weeks