Systemic Lupus Erythematosus
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of MK-6194 in adult participants with systemic lupus erythematosus.
Interventions
BIOLOGICALMK-6194
SC Injection
BIOLOGICALPlacebo
SC Injection
Sponsors
Merck Sharp & Dohme LLC
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
The main inclusion criteria include but are not limited to the following: * Has a diagnosis of systemic lupus erythematosus (SLE) ≥6 months prior to Screening. * Is taking at least 1 background therapy (1 immunosuppressant or dapsone and/or 1 antimalarial and/or oral corticosteroids) for SLE. * Has positive antinuclear antibody (+ANA; titer ≥1:80) or positive anti-double-strand deoxyribonucleic acid (dsDNA) antibody or positive anti-Smith (anti-Sm) antibody, or positive anti-Sjögren's Syndrome A (SSA)/Ro antibody. * Has the presence of at least 1 of the following manifestations of SLE: active lupus rash with Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) erythema and scale/hypertrophy combined score \>2, or \>2 tender and swollen joints in wrists, metacarpophalangeals (MCPs), or proximal interphalangeals (PIPs). * Has a hybrid Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) total score of ≥6 and clinical hybrid SLEDAI score of ≥4.
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving Systemic Lupus Erythematosus Responder Index (SRI-4) Response at Week 28 | Week 28 | The SRI was a composite index used to assess clinical improvement in participants with SLE. The SRI-4 response evaluated global improvement, any significant worsening in unaffected organ systems, and improvements in disease activity, without compromise to the participant's overall condition. SRI-4 response was binary and either achieved or not achieved by the participant, thus there was no associated score. Due to insufficient sample size, no statistical analysis was performed. Descriptive statistics in the form of counts calculated as percentages was reported. |
| Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 16 months | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. AEs were reported based on study treatment received by the participant at time of event. The number of participants who experienced one or more AEs was reported. |
| Number of Participants Who Discontinued Study Treatment Due to an AE | Up to approximately 16 months | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. AEs were reported based on study treatment received by the participant at time of event. The number of participants who discontinued study treatment due to an AE was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response at Week 28 | Week 28 | The BICLA response was a composite global measure of SLE disease activity. It distinguished between partial and complete improvement in all body systems. BICLA response was binary and either achieved or not achieved by the participant, thus there was no associated score. Due to insufficient sample size, no statistical analysis was performed. Descriptive statistics in the form of counts calculated as percentages was reported. |
| Number of Participants Achieving SRI-4 Response at Week 52 | Week 52 | The SRI was a composite index used to assess clinical improvement in participants with SLE. The SRI-4 response evaluated global improvement, any significant worsening in unaffected organ systems, and improvements in disease activity, without compromise to the participant's overall condition. SRI-4 response was binary and either achieved or not achieved by the participant, thus there was no associated score. Due to insufficient sample size, no statistical analysis was performed. Descriptive statistics in the form of counts calculated as percentages was reported. |
| Number of Participants Achieving BICLA Response at Week 52 | Week 52 | The BICLA response was a composite global measure of SLE disease activity. It distinguished between partial and complete improvement in all body systems. BICLA response was binary and either achieved or not achieved by the participant, thus there was no associated score. Due to insufficient sample size, no statistical analysis was performed. Descriptive statistics in the form of counts calculated as percentages was reported. |
| Number of Participants With a Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-50 Response at Week 28 | Week 28 | The CLASI-A score was used to evaluate lupus skin manifestations, with higher scores indicating increased disease severity and lower scores indicating less disease severity. CLASI-A scores of 0 to 9, 10 to 20, and 21 to 70 represented disease severity of mild, moderate, and severe, respectively. CLASI-50 was 50% improvement from baseline in the CLASI-A score. Due to insufficient sample size, no statistical analysis was performed. Descriptive statistics in the form of counts calculated as percentages was reported. |
| Number of Participants With a CLASI-50 Response at Week 52 | Week 52 | The CLASI-A score was used to evaluate lupus skin manifestations, with higher scores indicating increased disease severity and lower scores indicating less disease severity. CLASI-A scores of 0 to 9, 10 to 20, and 21 to 70 represented disease severity of mild, moderate, and severe, respectively. CLASI-50 was 50% improvement from baseline in the CLASI-A score. Due to insufficient sample size, no statistical analysis was performed. Descriptive statistics in the form of counts calculated as percentages was reported. |
| Change From Baseline in Swollen Joint Count at Week 28 | Baseline and Week 28 | The joint count score was an evaluation of 28 joints in which joints were assessed for presence or absence of swelling. The number of affected joints could have ranged from 0 to 28; with higher values corresponding to higher disease activity and lower values to less disease activity. Due to insufficient sample size, no statistical analysis was performed. Descriptive statistics in the form of means and standard deviations was reported. |
| Change From Baseline in Swollen Joint Count at Week 52 | Baseline and Week 52 | The joint count score was an evaluation of 28 joints in which joints were assessed for presence or absence of swelling. The number of affected joints could have ranged from 0 to 28; with higher values corresponding to higher disease activity and lower values to less disease activity. Due to insufficient sample size, no statistical analysis was performed. Descriptive statistics in the form of means and standard deviations was reported. |
| Change From Baseline in Tender Joint Count at Week 28 | Baseline and Week 28 | The joint count score was an evaluation of 28 joints in which joints were assessed for presence or absence of tenderness. The number of affected joints could have ranged from 0 to 28; with higher values corresponding to higher disease activity and lower values to less disease activity. Due to insufficient sample size, no statistical analysis was performed. Descriptive statistics in the form of means and standard deviations was reported. |
| Change From Baseline in Tender Joint Count at Week 52 | Baseline and Week 52 | The joint count score was an evaluation of 28 joints in which joints were assessed for presence or absence of tenderness. The number of affected joints could have ranged from 0 to 28; with higher values corresponding to higher disease activity and lower values to less disease activity. Due to insufficient sample size, no statistical analysis was performed. Descriptive statistics in the form of means and standard deviations was reported. |
| Change From Baseline in Swollen and Tender Joint Count at Week 28 | Baseline and Week 28 | The joint count score was an evaluation of 28 joints in which joints were assessed for presence or absence of swelling and presence or absence of tenderness. The number of affected joints could have ranged from 0 to 28; with higher values corresponding to higher disease activity and lower values to less disease activity. Due to insufficient sample size, no statistical analysis was performed. Descriptive statistics in the form of means and standard deviations was reported. |
| Change From Baseline in Swollen and Tender Joint Count at Week 52 | Baseline and Week 52 | The joint count score was an evaluation of 28 joints in which joints were assessed for presence or absence of swelling and presence or absence of tenderness. The number of affected joints could have ranged from 0 to 28; with higher values corresponding to higher disease activity and lower values to less disease activity. Due to insufficient sample size, no statistical analysis was performed. Descriptive statistics in the form of means and standard deviations was reported. |
| Change From Baseline in Oral Corticosteroid Dose at Week 28 | Baseline and Week 28 | Participants were assessed for corticosteroid dose change. Oral corticosteroid dose was based on prednisone or prednisone-equivalent dose. The oral corticosteroid dose at Week 28 was determined by the visit window of Week 28 (±7 days). Missing Week 28 dose was imputed with 0 if the participant completed Week 28 efficacy assessments. Oral corticosteroid doses as the weighted average of all doses taken at Week 28, weighted by the number of days each oral corticosteroid dose was administered was reported. Due to insufficient sample size, no statistical analysis was performed. Descriptive statistics in the form of means and standard deviations were reported. |
| Change From Baseline in Oral Corticosteroid Dose at Week 52 | Baseline and Week 52 | Participants were assessed for corticosteroid dose change. Oral corticosteroid dose was based on prednisone or prednisone-equivalent dose. The oral corticosteroid dose at Week 52 was determined by the visit window of Week 52 (±7 days). Missing Week 52 dose was imputed with 0 if the participant completed Week 52 efficacy assessments. Oral corticosteroid doses as the weighted average of all doses taken at Week 52, weighted by the number of days each oral corticosteroid dose was administered was reported. Due to insufficient sample size, no statistical analysis was performed. Descriptive statistics in the form of means and standard deviations were reported. |
| Cumulative Oral Corticosteroid Use Between Week 0 and Week 28 | Up to approximately 28 weeks | Participants were assessed for cumulative oral corticosteroid dose. Oral corticosteroid dose was based on prednisone or prednisone-equivalent dose. The cumulative oral corticosteroid dose at Week 28, calculated from Week 0 (Day 1) to Week 28 was reported. Due to insufficient sample size, no statistical analysis was performed. Descriptive statistics in the form of means and standard deviations were reported. |
| Cumulative Oral Corticosteroid Use Between Week 0 and Week 52 | Up to approximately 52 weeks | Participants were assessed for cumulative oral corticosteroid dose. Oral corticosteroid dose was based on prednisone or prednisone-equivalent dose. The cumulative oral corticosteroid dose at Week 52, calculated from Week 0 (Day 1) to Week 52 was reported. Due to insufficient sample size, no statistical analysis was performed. Descriptive statistics in the form of means and standard deviations were reported. |
| Number of Participants Who Achieved Low Level of Disease Activity (LLDAS) at Week 28 | Week 28 | LLDAS was a low disease activity state associated with significant protection against flares and organ damage accrual. It included both the measurement of disease activity and maintenance of immunosuppressive medications. LLDAS response was defined as hybrid SLEDAI ≤4 (with no activity in major organ systems), no new features of SLE activity compared with previous assessment, physician's global assessment (PGA) ≤1.0, current prednisone (or equivalent) dose ≤7.5 mg daily, and well-tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents, excluding investigational drugs. LLDAS response was binary and was either achieved or not achieved by the participant, thus there was no associated score. Due to insufficient sample size, no statistical analysis was performed. Descriptive statistics in the form of counts calculated as percentages was reported. |
| Number of Participants Who Achieved LLDAS at Week 52 | Week 52 | LLDAS was a low disease activity state associated with significant protection against flares and organ damage accrual. It included both the measurement of disease activity and maintenance of immunosuppressive medications. LLDAS response was defined as hybrid SLEDAI ≤4 (with no activity in major organ systems), no new features of SLE activity compared with previous assessment, physician's global assessment (PGA) ≤1.0, current prednisone (or equivalent) dose ≤7.5 mg daily, and well-tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents, excluding investigational drugs. LLDAS response was binary and was either achieved or not achieved by the participant, thus there was no associated score. Due to insufficient sample size, no statistical analysis was performed. Descriptive statistics in the form of counts calculated as percentages was reported. |
Countries
Argentina, Brazil, Canada, Chile, China, Colombia, France, Guatemala, Italy, Japan, Malaysia, Mexico, Philippines, Poland, Spain, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Pre-assignment details
During the main study, participants received MK-6194 (3 mg every 2 weeks \[q2w\] or every 4 weeks \[q4w\]) or placebo, administered subcutaneously (SC). Those who completed the main study entered the extension period. Participants who received MK-6194 continued their regimen, and participants who received placebo were re-randomized to MK-6194 3 mg q2w or MK-6194 3 mg q4w.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 40.8 Years STANDARD_DEVIATION 13.2 |
| Age, Customized Adults (Between 18 and 64 Years) | 145 Participants |
| Age, Customized From 65 to 84 Years | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Geographic Region Latin America/Eastern Europe | 26 Participants |
| Geographic Region Rest of the World | 25 Participants |
| Oral Corticosteroid Dose (Prednisone or Equivalent) at Randomization <10 mg/day | 26 Participants |
| Oral Corticosteroid Dose (Prednisone or Equivalent) at Randomization ≥10 mg/day | 69 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 12 Participants |
| Race (NIH/OMB) Asian | 13 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Sex: Female, Male Female | 139 Participants |
| Sex: Female, Male Male | 1 Participants |
| Total Hybrid Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Score at Screening <10 | 27 Participants |
| Total Hybrid Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Score at Screening ≥10 | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 49 | 1 / 51 | 0 / 2 | 0 / 4 | 0 / 2 | 0 / 4 |
| other Total, other adverse events | 29 / 49 | 25 / 49 | 22 / 51 | 1 / 2 | 1 / 4 | 0 / 2 | 1 / 4 |
| serious Total, serious adverse events | 5 / 49 | 5 / 49 | 4 / 51 | 0 / 2 | 0 / 4 | 0 / 2 | 1 / 4 |
Outcome results
None listed