Lupus Arthritis
Conditions
Keywords
Systemic Lupus Erythematosus (SLE), Lupus Arthritis, Laquinimod
Brief summary
The study aims to evaluate the safety and clinical effect of daily oral treatment with laquinimod capsules (0.5 milligrams \[mg\] and 1 mg) in participants with active lupus arthritis. Laquinimod is a novel immunomodulating drug which is currently in advanced stages of development by Teva Pharmaceuticals Ltd. for Multiple Sclerosis.
Interventions
DRUGLaquinimod
Laquinimod will be administered per dose and schedule specified in the arm description.
DRUGPlacebo
Placebo matching to laquinimod will be administered per schedule specified in the arm description.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Participants diagnosed with SLE. * Participants with active lupus arthritis as evident by at least 4 tender and 4 swollen joints at screening and baseline visits, and moderate or severe arthritis with active synovitis in at least 1 joint, with some loss of functional range of movement present at screening and baseline visits.
Exclusion criteria
* The participant's estimated glomerular filtration rate (eGFR) was less than or equal to 30 milliliters (mL)/minute/1.73 square meter (m\^2), as calculated by the Modification of Diet in Renal Disease (MDRD) formula at the screening visit. * Participants with severe, unstable and/or progressive central nervous system (CNS) lupus and/or associated with significant cognitive impairment (upon the investigators' judgement). * Participants with a clinically significant or unstable medical or surgical condition that, in the investigator's opinion, would preclude safe and complete study participation. * Women who are pregnant or nursing or who intend to be during the study period. * Women of child-bearing potential who do not practice an acceptable method of birth control.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | Baseline up to Week 16 | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'. |
| Percent Change From Baseline in Swollen Joint Count at Week 12 | Baseline, Week 12 | The number of swollen joints was used to assess lupus arthritis activity. Joint swelling was defined as soft tissue swelling that was detectable along the joint margins. 66 joints were examined for swelling. These joints include the temporomandibular (n = 2), sternoclavicular (n =2), acromioclavicular (n = 2), shoulder (n = 2), elbow (n = 2), wrist (n = 2), metacarpophalageal (n= 10), interphalangeal of thumb (n = 2), distal interphalangeal (n = 8), proximal interphalangeal (n =8), knee (n = 2), ankle mortise (n = 2), ankle tarsus (n = 2), metatarsophalangeal (n = 10), interphalangeal of great toe (n = 2), and proximal/distal interphalangeal of the toes (n = 8). |
| Percent Change From Baseline in Tender Joint Count at Week 12 | Baseline, Week 12 | The number of tender joints was used to assess lupus arthritis activity. Joint tenderness was defined as the presence or absence of tenderness and/or pain in a joint at rest with pressure or on passive movement of the joint and joint manipulation. 68 joints were examined for tenderness. These joints include the temporomandibular (n = 2), sternoclavicular (n =2), acromioclavicular (n = 2), shoulder (n = 2), elbow (n = 2), wrist (n = 2), metacarpophalageal (n= 10), interphalangeal of thumb (n = 2), distal interphalangeal (n = 8), proximal interphalangeal (n =8), hip (n = 2), knee (n = 2), ankle mortise (n = 2), ankle tarsus (n = 2), metatarsophalangeal (n = 10), interphalangeal of great toe (n = 2), and proximal/distal interphalangeal of the toes (n = 8). |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received 2 capsules of placebo matched to laquinimod orally once daily for 12 weeks. | 26 |
| Laquinimod 0.5 mg Participants received 1 capsule of laquinimod 0.5 mg and 1 capsule of placebo matched to laquinimod orally once daily for 12 weeks. | 28 |
| Laquinimod 1 mg Participants received 2 capsules of laquinimod 0.5 mg orally once daily for 12 weeks. | 28 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 3 | 6 |
| Overall Study | Lost to Follow-up | 2 | 1 | 1 |
| Overall Study | Treatment Failure | 0 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Laquinimod 0.5 mg | Laquinimod 1 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 48.1 years STANDARD_DEVIATION 13.5 | 46.6 years STANDARD_DEVIATION 12 | 46.8 years STANDARD_DEVIATION 13.4 | 47.1 years STANDARD_DEVIATION 12.8 |
| Race/Ethnicity, Customized Asian | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 3 Participants | 9 Participants | 16 Participants |
| Race/Ethnicity, Customized Hispanic | 6 Participants | 8 Participants | 8 Participants | 22 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 16 Participants | 14 Participants | 10 Participants | 40 Participants |
| Sex: Female, Male Female | 24 Participants | 25 Participants | 26 Participants | 75 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 2 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 29 | 0 / 28 |
| other Total, other adverse events | 17 / 25 | 24 / 29 | 18 / 28 |
| serious Total, serious adverse events | 0 / 25 | 4 / 29 | 2 / 28 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.
Time frame: Baseline up to Week 16
Population: Safety analysis set included all randomized participants who received at least 1 dose of study drug. In this set, treatment was assigned based upon the treatment actually received regardless of the assigned treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs) | 21 Participants |
| Laquinimod 0.5 mg | Number of Participants With Adverse Events (AEs) | 29 Participants |
| Laquinimod 1 mg | Number of Participants With Adverse Events (AEs) | 25 Participants |
Primary
Percent Change From Baseline in Swollen Joint Count at Week 12
The number of swollen joints was used to assess lupus arthritis activity. Joint swelling was defined as soft tissue swelling that was detectable along the joint margins. 66 joints were examined for swelling. These joints include the temporomandibular (n = 2), sternoclavicular (n =2), acromioclavicular (n = 2), shoulder (n = 2), elbow (n = 2), wrist (n = 2), metacarpophalageal (n= 10), interphalangeal of thumb (n = 2), distal interphalangeal (n = 8), proximal interphalangeal (n =8), knee (n = 2), ankle mortise (n = 2), ankle tarsus (n = 2), metatarsophalangeal (n = 10), interphalangeal of great toe (n = 2), and proximal/distal interphalangeal of the toes (n = 8).
Time frame: Baseline, Week 12
Population: Modified intent-to-treat (mITT) analysis set included all participants who were randomly assigned to a treatment, regardless of which treatment they actually received, excluding observations after treatment failure. Here 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Swollen Joint Count at Week 12 | -36.9 percent change | Standard Deviation 78.1 |
| Laquinimod 0.5 mg | Percent Change From Baseline in Swollen Joint Count at Week 12 | -36.7 percent change | Standard Deviation 47 |
| Laquinimod 1 mg | Percent Change From Baseline in Swollen Joint Count at Week 12 | -40.5 percent change | Standard Deviation 55.6 |
Primary
Percent Change From Baseline in Tender Joint Count at Week 12
The number of tender joints was used to assess lupus arthritis activity. Joint tenderness was defined as the presence or absence of tenderness and/or pain in a joint at rest with pressure or on passive movement of the joint and joint manipulation. 68 joints were examined for tenderness. These joints include the temporomandibular (n = 2), sternoclavicular (n =2), acromioclavicular (n = 2), shoulder (n = 2), elbow (n = 2), wrist (n = 2), metacarpophalageal (n= 10), interphalangeal of thumb (n = 2), distal interphalangeal (n = 8), proximal interphalangeal (n =8), hip (n = 2), knee (n = 2), ankle mortise (n = 2), ankle tarsus (n = 2), metatarsophalangeal (n = 10), interphalangeal of great toe (n = 2), and proximal/distal interphalangeal of the toes (n = 8).
Time frame: Baseline, Week 12
Population: The mITT analysis set included all participants who were randomly assigned to a treatment, regardless of which treatment they actually received, excluding observations after treatment failure. Here 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Tender Joint Count at Week 12 | -8.5 percent change | Standard Deviation 81.3 |
| Laquinimod 0.5 mg | Percent Change From Baseline in Tender Joint Count at Week 12 | -31.4 percent change | Standard Deviation 53.1 |
| Laquinimod 1 mg | Percent Change From Baseline in Tender Joint Count at Week 12 | -42.0 percent change | Standard Deviation 37.8 |