Systemic Lupus Erythematosus
Conditions
Keywords
Autoimmune Disease, BTLA B and T Lymphocyte attenuator, Immune checkpoint, Inhibitory checkpoint agonist antibody, Lupus
Brief summary
The main purpose of this study is to assess the efficacy and safety of LY3361237 in participants with at least moderately active systemic lupus erythematosus (SLE). Study will last up to 34 weeks and may include up to 15 visits.
Interventions
DRUGLY3361237
Administered SC
DRUGPlacebo
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Are diagnosed with SLE at least 24 weeks before Day 1 of study * Have documentation of having a score of 10 or more points on the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for SLE * Have a SLEDAI-2K score ≥6 at screening (Day 1) and clinical Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≥4 (not including any items related to laboratory values) at randomization (Day 2) * Must be receiving at least 1 background standard-of-care medication for SLE
Exclusion criteria
* Participants are excluded if they have received any of the following medications or therapies within the indicated timeframe prior to the randomization visit (Day 2). * Are currently receiving oral corticosteroids at doses \>20 mg per day of prednisone (or equivalent) or have adjusted the dosage of corticosteroids within 2 weeks before starting study treatment * Have received parenteral corticosteroids within 12 weeks before starting study treatment or are expected to require parenteral corticosteroids during the study * Have a current or recent acute, active infection * Have had a serious, chronic, recurring conditions of herpes simplex, herpes zoster, recurring cellulitis, chronic osteomyelitis) * Have human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV), hepatitis C infection (HCV), active tuberculosis (TB) * Have active fibromyalgia or active occurrence of an inflammatory condition that, in the investigator's opinion, would make it difficult to appropriately assess SLE activity for the purposes of this study * Have experienced a cardiac event within 24 weeks to 12 months prior to screening * Have a history of clinically significant or uncontrolled illness that in the opinion of the investigator could put the participant at risk to participate in the study * Are, in the judgment of the investigator, actively suicidal and therefore deemed to be at significant risk for suicide * Are pregnant or are intending to become pregnant or to breastfeed at any time in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Arthritis and/or Rash at Baseline Who Achieve Remission of Arthritis and/or Rash | Week 24 | Remission of arthritis and/or rash is defined by the following: if only arthritis is present at baseline, then the primary endpoint is met if arthritis is absent at Week 24; if only rash is present at baseline, then the primary endpoint is met if rash is absent at Week 24; if both arthritis and rash are present at baseline, then the primary endpoint is met if either arthritis, or rash, or both arthritis and rash are absent at Week 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve Systemic Lupus Erythematosus Disease Activity Index-4 (SLEDAI-4) Response | Week 24 | Percentage of participants who achieved SLEDAI-4 response was assessed. A SLEDAI-4 response is defined as a ≥ 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score from baseline. The SLEDAI-2K score range is from a minimum of 0 to a maximum of 105 (higher scores represent higher disease activity). |
| Percentage of Participants Who Achieve Systemic Lupus Erythematosus Responder Index-4 (SRI-4 Response) | Week 24 | Percentage of participants who achieved SRI-4 response was assessed. SRI-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[10 mm\] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity. |
| Pharmacokinetics (PK): Steady-state Trough Serum Concentration of LY3361237 at Week 24 | Week 24 | PK: Steady-state trough serum concentration of LY3361237 at Week 24 was assessed. |
Countries
Argentina, Czechia, France, Mexico, Poland, Puerto Rico, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 450 mg - LY3361237 Participants received 450 mg of LY3361237 administered SC Q2W along with their usual SOC medication for 24 weeks. | 42 |
| Placebo Participants received placebo administered SC Q2W along with their usual SOC medication for 24 weeks. | 43 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | 450 mg - LY3361237 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 44.2 years STANDARD_DEVIATION 12.1 | 43.3 years STANDARD_DEVIATION 11.1 | 43.8 years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 25 Participants | 27 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 15 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 7 Participants | 7 Participants | 14 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 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 | 30 Participants | 30 Participants | 60 Participants |
| Region of Enrollment Argentina | 7 Participants | 8 Participants | 15 Participants |
| Region of Enrollment Mexico | 8 Participants | 7 Participants | 15 Participants |
| Region of Enrollment Poland | 6 Participants | 7 Participants | 13 Participants |
| Region of Enrollment Taiwan | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment United States | 18 Participants | 19 Participants | 37 Participants |
| Sex: Female, Male Female | 38 Participants | 42 Participants | 80 Participants |
| Sex: Female, Male Male | 4 Participants | 1 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 43 |
| other Total, other adverse events | 28 / 42 | 27 / 43 |
| serious Total, serious adverse events | 5 / 42 | 1 / 43 |
Outcome results
Primary
Percentage of Participants With Arthritis and/or Rash at Baseline Who Achieve Remission of Arthritis and/or Rash
Remission of arthritis and/or rash is defined by the following: if only arthritis is present at baseline, then the primary endpoint is met if arthritis is absent at Week 24; if only rash is present at baseline, then the primary endpoint is met if rash is absent at Week 24; if both arthritis and rash are present at baseline, then the primary endpoint is met if either arthritis, or rash, or both arthritis and rash are absent at Week 24.
Time frame: Week 24
Population: All participants who received at least 1 dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 450 mg - LY3361237 | Percentage of Participants With Arthritis and/or Rash at Baseline Who Achieve Remission of Arthritis and/or Rash | 11.9 Percentage of participants |
| Placebo | Percentage of Participants With Arthritis and/or Rash at Baseline Who Achieve Remission of Arthritis and/or Rash | 20.9 Percentage of participants |
Secondary
Percentage of Participants Who Achieve Systemic Lupus Erythematosus Disease Activity Index-4 (SLEDAI-4) Response
Percentage of participants who achieved SLEDAI-4 response was assessed. A SLEDAI-4 response is defined as a ≥ 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score from baseline. The SLEDAI-2K score range is from a minimum of 0 to a maximum of 105 (higher scores represent higher disease activity).
Time frame: Week 24
Population: All participants who received at least 1 dose of the study drug and had evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 450 mg - LY3361237 | Percentage of Participants Who Achieve Systemic Lupus Erythematosus Disease Activity Index-4 (SLEDAI-4) Response | 9.5 Percentage of participants |
| Placebo | Percentage of Participants Who Achieve Systemic Lupus Erythematosus Disease Activity Index-4 (SLEDAI-4) Response | 16.3 Percentage of participants |
Secondary
Percentage of Participants Who Achieve Systemic Lupus Erythematosus Responder Index-4 (SRI-4 Response)
Percentage of participants who achieved SRI-4 response was assessed. SRI-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[10 mm\] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity.
Time frame: Week 24
Population: All participants who received at least 1 dose of study drug and have evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 450 mg - LY3361237 | Percentage of Participants Who Achieve Systemic Lupus Erythematosus Responder Index-4 (SRI-4 Response) | 9.5 Percentage of participants |
| Placebo | Percentage of Participants Who Achieve Systemic Lupus Erythematosus Responder Index-4 (SRI-4 Response) | 16.3 Percentage of participants |
Secondary
Pharmacokinetics (PK): Steady-state Trough Serum Concentration of LY3361237 at Week 24
PK: Steady-state trough serum concentration of LY3361237 at Week 24 was assessed.
Time frame: Week 24
Population: All participants who received at least one dose of LY3361237 and had evaluable PK data for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 450 mg - LY3361237 | Pharmacokinetics (PK): Steady-state Trough Serum Concentration of LY3361237 at Week 24 | 144 micrograms per milliliter (μg/mL) | Standard Deviation 73.8 |