Rheumatoid Arthritis
Conditions
Brief summary
The purpose of this study is to evaluate the serum concentration of tabalumab after the administration using either prefilled syringe or auto-injector after the initial loading dose and after 12 weeks of treatment. Treatment period is followed by 40 weeks optional safety extension.
Interventions
Administered SC by prefilled syringe
Administered SC by auto-injector
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ambulatory males or females ≥18 years of age * Diagnosis of adult-onset RA * Active RA (at least 8/68 tender and at least 8/66 swollen joints) * Screening C-reactive protein (CRP) \>1.2 times the upper limit of normal (ULN) or a screening erythrocyte sedimentation rate (ESR) \>28 millimeters per hour (mm/hr) * Documented history of, or current, positive rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibody (anti-CCP Ab) test * Regular use of methotrexate (MTX) for at least 12 weeks and stable dose (10 to 25 mg/week) for at least 8 weeks prior to baseline * American College of Rheumatology (ACR) functional class I, II, or III * Able and willing to inject tabalumab by themselves (or have an assistant who will inject tabalumab) and able and willing to complete all study procedures * Able and willing to have blood drawn for pharmacokinetic (PK) sampling
Exclusion criteria
* Use of oral corticosteroids at average daily doses of \>10 milligrams per day (mg/day) of prednisone or its equivalent within 6 weeks prior to baseline * Injection of any parenteral (including intraarticular) corticosteroid within 6 weeks of baseline * Have previously discontinued treatment with a biologic disease-modifying antirheumatic drug (DMARD) or a novel drug that interrupts cytokine signaling \[for example, Janus kinase (JAK) inhibitors\] due to insufficient efficacy * Participants who had discontinued biologic DMARDS for reasons other than efficacy will not be excluded but must have done so prior to baseline * Participants who discontinued a JAK inhibitor for lack of efficacy * Participants who discontinued a JAK inhibitor for reasons other than efficacy will not be excluded, but must have done so prior to baseline for 21 days * Previous severe reaction to any biologic therapy that, in the opinion of the Investigator, would pose an unacceptable risk to the participant if participating in the study * Have had an inadequate response to treatment with 3 or more of the following DMARDs prescribed alone or in combination at approved doses for a minimum of 90 days: leflunomide, azathioprine, cyclosporine, and/or sulfasalazine * Use of other DMARDs (for example, gold salts, cyclosporin, azathioprine, or any other immunosuppressives) other than MTX, hydroxychloroquine, chloroquine, or sulfasalazine, or the use of a JAK inhibitor in the 8 weeks prior to baseline
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Tabalumab After Loading Dose | Days 4, 7, 9, 11, and 14 after loading dose administered |
| PK: Area Under the Concentration Time Curve From Time 0 to 14 Days [AUC(0-14)] | Days 4, 7, 9, 11, and 14 after loading dose administered |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline to 12-Week Endpoint in American College of Rheumatology (ACR-N) Index | Baseline, Week 12 |
| Change From Baseline to 12-Week Endpoint in Disease Activity Score Based on a 28-Joint Count and C-Reactive Protein (DAS28-CRP) Level | Baseline, Week 12 |
| Percentage of Participants Achieving European League Against Rheumatism Responder Index Based on the 28-Joint Count (EULAR-28) | Week 12 |
| Change From Baseline to 12-Week Endpoint in Achieving American College of Rheumatology (ACR) Core Set | Baseline, Week 12 |
| Number of Operation Failures | Week 12 |
| Change From Baseline Score in Subcutaneous Administration Assessment Questionnaire (SQAAQ) | Baseline, Weeks 4 and 8 |
| Number of Participants Developing Anti-Tabalumab Antibodies | Week 12 |
| Percentage of Participants Achieving ACR Response | Week 12 |
Countries
Argentina, Czechia, Poland, Puerto Rico, Russia, United States
Participant flow
Pre-assignment details
The study was to include a 12-week treatment period, optional 40-week safety extension, and post-treatment follow-up (at least 24 weeks). At the time of early study termination, all participants who had received tabalumab discontinued dosing and then completed the post-treatment follow-up period. No one entered the 40-week safety extension period.
Participants by arm
| Arm | Count |
|---|---|
| Tabalumab Auto-Injector Tabalumab: Using auto-injectors, participants received a 180 mg loading dose administered at Week 0 as 2 SC injections (90 mg each). Participants also received a 90 mg SC injection Q2W until early study termination (up to Week 6). | 4 |
| Tabalumab Prefilled Syringe Tabalumab: Using prefilled syringes, participants received a 180 mg loading dose administered at Week 0 as 2 SC injections (90 mg each). Participants also received a 90 mg SC injection Q2W until early study termination (up to Week 6). | 4 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Sponsor Decision | 3 | 4 |
Baseline characteristics
| Characteristic | Tabalumab Auto-Injector | Total | Tabalumab Prefilled Syringe |
|---|---|---|---|
| Age, Customized 43.3 to 65.4 years | 4 participants | 8 participants | 4 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 7 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 7 Participants | 3 Participants |
| Region of Enrollment United States | 4 Participants | 8 Participants | 4 Participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 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 | 0 / 4 | 1 / 4 | 0 / 4 | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 |
Outcome results
Primary
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Tabalumab After Loading Dose
Time frame: Days 4, 7, 9, 11, and 14 after loading dose administered
Population: No participant had outcome measure data analyzed due to the termination of the trial and an insufficient sample size.
Primary
PK: Area Under the Concentration Time Curve From Time 0 to 14 Days [AUC(0-14)]
Time frame: Days 4, 7, 9, 11, and 14 after loading dose administered
Population: No participant had outcome measure data analyzed due to the termination of the trial and an insufficient sample size.
Secondary
Change From Baseline Score in Subcutaneous Administration Assessment Questionnaire (SQAAQ)
Time frame: Baseline, Weeks 4 and 8
Population: No participant had outcome measure data analyzed due to the termination of the trial and an insufficient sample size.
Secondary
Change From Baseline to 12-Week Endpoint in Achieving American College of Rheumatology (ACR) Core Set
Time frame: Baseline, Week 12
Population: No participant had outcome measure data analyzed due to the termination of the trial and an insufficient sample size.
Secondary
Change From Baseline to 12-Week Endpoint in Disease Activity Score Based on a 28-Joint Count and C-Reactive Protein (DAS28-CRP) Level
Time frame: Baseline, Week 12
Population: No participant had outcome measure data analyzed due to the termination of the trial and an insufficient sample size.
Secondary
Number of Operation Failures
Time frame: Week 12
Population: No participant had outcome measure data analyzed due to the termination of the trial and an insufficient sample size.
Secondary
Number of Participants Developing Anti-Tabalumab Antibodies
Time frame: Week 12
Population: No participant had outcome measure data analyzed due to the termination of the trial and an insufficient sample size.
Secondary
Percentage of Participants Achieving ACR Response
Time frame: Week 12
Population: No participant had outcome measure data analyzed due to the termination of the trial and an insufficient sample size.
Secondary
Percentage of Participants Achieving European League Against Rheumatism Responder Index Based on the 28-Joint Count (EULAR-28)
Time frame: Week 12
Population: No participant had outcome measure data analyzed due to the termination of the trial and an insufficient sample size.
Secondary
Percent Change From Baseline to 12-Week Endpoint in American College of Rheumatology (ACR-N) Index
Time frame: Baseline, Week 12
Population: No participant had outcome measure data analyzed due to the termination of the trial and an insufficient sample size.