Systemic Lupus Erythematosus
Conditions
Brief summary
This study evaluates the impact of 13 bi-weekly intravenous infusions of RSLV-132 on the cutaneous manifestations in subjects with systemic lupus erythematosus.
Interventions
DRUGRSLV-132
RNase-Fc fusion protein
DRUGPlacebo
Saline placebo
Sponsors
Resolve Therapeutics
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 70 Years
Healthy volunteers
No
Inclusion criteria
* CLASI score greater than or equal to 10 at Baseline * Positive for one or more RNA autoantibodies
Exclusion criteria
1. severe, active central nervous system (CNS) involvement at Screening; 2. severe renal involvement at Screening (urine protein/creatinine ratio of \>200 mg/mmol, or an estimated creatinine clearance of \<30 mL/min); 3. use of cyclophosphamide within 3 months of the Baseline visit; 4. use of rituximab within 6 months of the Baseline visit; 5. use of belimumab within 3 months of the Baseline visit; 6. use of background medications within 1 month of Baseline in excess of: i. mycophenolate mofetil \> 3 g/day; ii. azathioprine \> 200 mg/day; iii. methotrexate \> 25 mg/day; iv. hydroxychloroquine \> 400 mg/day; v. prednisone (or equivalent) \> 15 mg/day; 7. use of an intravenous steroid pulse within 2 months of Baseline; 8. use of an intramuscular steroid injection within 1 month of Baseline; 9. change in SLE medications within 1 month of Baseline; 10. the presence of a clinically significant infection in the judgement of the Investigator within seven days prior to the receipt of the first dose of study drug; 11. positive viral load test for hepatitis B, C, or HIV at Screening; 12. participation in another clinical trial with receipt of an investigational product within 3 months or 5 half- lives, of last administration (whichever is longer) from Baseline; 13. positive pregnancy test at Screening or at Baseline; 14. female subjects currently breast feeding at Baseline; 15. inability or unwillingness to comply with protocol-specified procedures which, in the opinion of the Investigator, would make the subject unsuitable for study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Improvement Compared to Placebo. | Baseline and Days 29, 57, 85, 99, 113, 127, 141, 155, 169 | Mean change from baseline (from baseline to Day 85; or baseline to Day 169) in CLASI activity scores (Last Observation Carried Forward \[LOCF\] post censoring values). The CLASI is a single-page tool that separately quantifies disease activity and damage. For the activity score, points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. The total score represents the sum of the individual scores and ranges from 0 to 70. Higher scores are awarded for more severe manifestations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving a 50% Improvement in CLASI Activity Score | Baseline and Days 29, 57, 85, 99, 113, 127, 141, 155, 169 | Percentage of participants achieving a 50% improvement in CLASI activity score at Day 85 and Day 169 (LOCF post censoring due to use of exclusionary medications) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RSLV-132 10 mg/kg RSLV-132
RSLV-132: RNase-Fc fusion protein | 42 |
| Placebo Saline placebo
Placebo: Saline placebo | 22 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 4 |
| Overall Study | Exclusion criteria met | 2 | 0 |
| Overall Study | Lost to Follow-up | 4 | 1 |
| Overall Study | Physician Decision | 3 | 1 |
| Overall Study | Subject schedule | 0 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | RSLV-132 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 45.3 years STANDARD_DEVIATION 12.8 | 45.2 years STANDARD_DEVIATION 11.6 | 45.3 years STANDARD_DEVIATION 12.3 |
| CLASI Activity Total Score | 24.1 Score on a scale STANDARD_DEVIATION 9.9 | 22.4 Score on a scale STANDARD_DEVIATION 7.9 | 23.5 Score on a scale STANDARD_DEVIATION 9.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 4 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 18 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Oral corticosteroid dose 0 | 20 Participants | 7 Participants | 27 Participants |
| Oral corticosteroid dose >0 and less than or equal to 7.5 mg/kg | 6 Participants | 5 Participants | 11 Participants |
| Oral corticosteroid dose >7.5 | 16 Participants | 10 Participants | 26 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 11 Participants | 27 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 | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 22 Participants | 11 Participants | 33 Participants |
| Region of Enrollment United States | 32 participants | 22 participants | 54 participants |
| Sex: Female, Male Female | 39 Participants | 22 Participants | 61 Participants |
| Sex: Female, Male Male | 3 Participants | 0 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 22 |
| other Total, other adverse events | 36 / 42 | 20 / 22 |
| serious Total, serious adverse events | 3 / 42 | 5 / 22 |
Outcome results
Primary
Mean Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Improvement Compared to Placebo.
Mean change from baseline (from baseline to Day 85; or baseline to Day 169) in CLASI activity scores (Last Observation Carried Forward \[LOCF\] post censoring values). The CLASI is a single-page tool that separately quantifies disease activity and damage. For the activity score, points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. The total score represents the sum of the individual scores and ranges from 0 to 70. Higher scores are awarded for more severe manifestations.
Time frame: Baseline and Days 29, 57, 85, 99, 113, 127, 141, 155, 169
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RSLV-132 | Mean Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Improvement Compared to Placebo. | Day 85 | -6.2 Scores on a scale | Standard Deviation 6.7 |
| RSLV-132 | Mean Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Improvement Compared to Placebo. | Day 169 | -6.2 Scores on a scale | Standard Deviation 8.5 |
| Placebo | Mean Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Improvement Compared to Placebo. | Day 85 | -6.5 Scores on a scale | Standard Deviation 6.2 |
| Placebo | Mean Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Improvement Compared to Placebo. | Day 169 | -5.7 Scores on a scale | Standard Deviation 7 |
Comparison: Change from baseline at Day 85 RSLV-132 versus placebop-value: 0.84595% CI: [-3.42, 4.15]t-test, 2 sided
Comparison: Change from baseline at Day 169 RSLV-132 versus placebop-value: 0.81895% CI: [-4.66, 3.7]t-test, 2 sided
Secondary
Percentage of Participants Achieving a 50% Improvement in CLASI Activity Score
Percentage of participants achieving a 50% improvement in CLASI activity score at Day 85 and Day 169 (LOCF post censoring due to use of exclusionary medications)
Time frame: Baseline and Days 29, 57, 85, 99, 113, 127, 141, 155, 169
Population: On Day 169, a post hoc exploratory subgroup analysis was performed on participants with severe CLASI and severe SLE Disease Activity Index (SLEDAI-2K) scores at baseline. The SLEDAI-2K is a clinical index for the assessment of lupus disease activity in the previous 30 days. It consists of 24 weighted clinical and laboratory variables of nine organ systems. Scores of the descriptors range from 1 to 8, the total possible score is 105. A higher score indicates more severe disease.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RSLV-132 | Percentage of Participants Achieving a 50% Improvement in CLASI Activity Score | Day 85 | 11 Participants |
| RSLV-132 | Percentage of Participants Achieving a 50% Improvement in CLASI Activity Score | Day 169 All Participants | 14 Participants |
| RSLV-132 | Percentage of Participants Achieving a 50% Improvement in CLASI Activity Score | Day 169 Participants with Severe CLASI >/=21 | 7 Participants |
| RSLV-132 | Percentage of Participants Achieving a 50% Improvement in CLASI Activity Score | Day 169 Participants with Severe SLEDAI >/=9 | 4 Participants |
| Placebo | Percentage of Participants Achieving a 50% Improvement in CLASI Activity Score | Day 169 Participants with Severe SLEDAI >/=9 | 1 Participants |
| Placebo | Percentage of Participants Achieving a 50% Improvement in CLASI Activity Score | Day 85 | 2 Participants |
| Placebo | Percentage of Participants Achieving a 50% Improvement in CLASI Activity Score | Day 169 Participants with Severe CLASI >/=21 | 3 Participants |
| Placebo | Percentage of Participants Achieving a 50% Improvement in CLASI Activity Score | Day 169 All Participants | 5 Participants |
Post Hoc
Percentage of Participants With a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response
Percentage of participants with a BICLA response on Day 169. This is a composite responder index incorporating the BILAG-2004, SLEDAI-2K and PGA responses. The BILAG-2004 index, an organ-based transitional activity instrument, provides disease activity scorings across nine organ systems (constitutional, mucocutaneous, neuropsychiatry, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal and hematological) on an ordinal scale (A to E) based on the physician's intention-to-treat premise. Grade A represents the most active and Grade E the least active disease. The PGA is measured on a 0 to 100 mm scale with score 0 to be No Disease Activity and score 100 to be the most Severe Disease Activity.
Time frame: Baseline and Day 169
Population: A subgroup analysis was also performed on participants with severe CLASI and severe SLEDAI scores
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RSLV-132 | Percentage of Participants With a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response | Day 169 All Participants | 10 Participants |
| RSLV-132 | Percentage of Participants With a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response | Day 169 Participants with Severe CLASI >/=21 | 5 Participants |
| RSLV-132 | Percentage of Participants With a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response | Day 169 Participants with Severe SLEDAI >/=9 | 4 Participants |
| Placebo | Percentage of Participants With a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response | Day 169 All Participants | 4 Participants |
| Placebo | Percentage of Participants With a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response | Day 169 Participants with Severe CLASI >/=21 | 1 Participants |
| Placebo | Percentage of Participants With a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response | Day 169 Participants with Severe SLEDAI >/=9 | 1 Participants |
Post Hoc
Percentage of Participants With SRI-4 Response
Percentage of participants with an Systemic Lupus Erythematous Responder Index (SRI) 4 response on Day 169. This is a composite responder index incorporating the British Isles Lupus Assessment Group (BILAG) 2004, SLEDAI-2K and Physician Global Assessment (PGA) responses. The BILAG-2004 index, an organ-based transitional activity instrument, provides disease activity scorings across nine organ systems (constitutional, mucocutaneous, neuropsychiatry, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal and hematological) on an ordinal scale (A to E) based on the physician's intention-to-treat premise. Grade A represents the most active and Grade E the least active disease. The Physician's Global Assessment is measured on a 0 to 100 mm scale with score 0 to be No Disease Activity and score 100 to be the most Severe Disease Activity.
Time frame: Baseline and Day 169
Population: A subgroup analysis was also performed on participants with severe CLASI and severe SLEDAI scores
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RSLV-132 | Percentage of Participants With SRI-4 Response | Day 169 All participants | 11 Participants |
| RSLV-132 | Percentage of Participants With SRI-4 Response | Day 169 Participants with Severe CLASI >/=21 | 7 Participants |
| RSLV-132 | Percentage of Participants With SRI-4 Response | Day 169 Participants with Severe SLEDAI >/=9 | 8 Participants |
| Placebo | Percentage of Participants With SRI-4 Response | Day 169 All participants | 7 Participants |
| Placebo | Percentage of Participants With SRI-4 Response | Day 169 Participants with Severe CLASI >/=21 | 1 Participants |
| Placebo | Percentage of Participants With SRI-4 Response | Day 169 Participants with Severe SLEDAI >/=9 | 4 Participants |