A Phase 2a, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of MK-6194 in Adult Participants With Systemic Lupus Erythematosus
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 149
- 试验地点
- 127
- 主要终点
- Number of Participants Achieving Systemic Lupus Erythematosus Responder Index (SRI-4) Response at Week 28
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of MK-6194 in adult participants with systemic lupus erythematosus.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Has a concurrent clinically significant disease or clinically relevant laboratory abnormalities, or a history of any illness or medical condition that might confound the results of the study or poses an additional risk to the participant by their participation in the study.
- •Has symptomatic heart failure (New York Heart Association Class III or IV) or myocardial infarction or unstable angina pectoris within 6 months prior to Screening.
- •Has a severe chronic pulmonary disease requiring oxygen therapy.
- •Has a transplanted organ which requires continued immunosuppression.
- •Has a known systemic hypersensitivity to interleukin-2 (IL-2), or modified IL-2 including MK-6194, or its inactive ingredients.
- •Has a known history of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly.
- •Has drug-induced cutaneous lupus erythematosus (CLE) and/or drug-induced SLE in the setting of continued treatment with a causative agent.
- •Has active or unstable neuropsychiatric lupus including but not limited to the following: seizure, new or worsening impaired level of consciousness, psychosis, delirium or confused state, aseptic meningitis, cranial neuropathy, cerebrovascular accident, ascending or transverse myelitis, chorea, cerebellar ataxia, mononeuritis multiplex, or demyelinating syndromes.
- •Has a diagnosis of antiphospholipid syndrome (APS) with history of vascular thrombosis, catastrophic APS, or pregnancy morbidity within 6 months prior to Screening.
- •Has a history of any malignancy, except for successfully treated non-melanoma skin cancer or localized carcinoma in situ of the cervix.
- •Has an active or clinically significant infection requiring hospitalization or treatment with anti-infectives.
- •Has evidence of active tuberculosis (TB), latent TB, or inadequately treated TB.
- •Has confirmed or suspected coronavirus disease of 2019 (COVID-19) infection.
- •Has had major surgery within 3 months prior to Screening or has a major surgery planned during the study.
- •Is taking more than 1 immunosuppressant.
- •Is taking more than 1 oral nonsteroidal anti-inflammatory drug (NSAID), excluding low-dose aspirin (<350 mg/day), or is taking daily oral NSAID at greater than the maximum recommended dosage.
- •Is currently on any chronic systemic (oral or intravenous [IV]) anti-infective therapy for chronic active infection (such as pneumocystis, cytomegalovirus, herpes zoster, or atypical mycobacteria).
研究组 & 干预措施
Placebo
Participants receive SC placebo q2w.
干预措施: Placebo (Biological)
MK-6194 3 mg Q4W
Participants receive SC MK-6194 3 mg every 4 weeks (q4w).
干预措施: MK-6194 (Biological)
MK-6194 3 mg Q2W (Main Study) / MK-6194 3 mg Q2W (Extension Period)
After completing 52 weeks of treatment with SC MK-6194 administered 3 mg q2w in the main study, participants continue to receive SC MK-6194 3 mg q2w in the extension period.
干预措施: MK-6194 (Biological)
MK-6194 3 mg Q2W
Participants receive subcutaneous (SC) MK-6194 3 mg every 2 weeks (q2w).
干预措施: MK-6194 (Biological)
Placebo (Main Study)/ MK-6194 3 mg Q2W (Extension Period)
After completing 52 weeks of treatment with SC placebo administered q2w in the main study, participants are re-randomized to receive SC MK-6194 3 mg q2w in the extension period.
干预措施: MK-6194 (Biological)
Placebo (Main Study)/ MK-6194 3 mg Q2W (Extension Period)
After completing 52 weeks of treatment with SC placebo administered q2w in the main study, participants are re-randomized to receive SC MK-6194 3 mg q2w in the extension period.
干预措施: Placebo (Biological)
Placebo (Main Study)/ MK-6194 3 mg Q4W (Extension Period)
After completing 52 weeks of treatment with SC placebo administered q2w in the main study, participants are re-randomized to receive SC MK-6194 3 mg q4w in the extension period.
干预措施: Placebo (Biological)
Placebo (Main Study)/ MK-6194 3 mg Q4W (Extension Period)
After completing 52 weeks of treatment with SC placebo administered q2w in the main study, participants are re-randomized to receive SC MK-6194 3 mg q4w in the extension period.
干预措施: MK-6194 (Biological)
MK-6194 3 mg Q4W (Main Study) / MK-6194 3 mg Q4W (Extension Period)
After completing 52 weeks of treatment with SC MK-6194 administered 3 mg q4w in the main study, participants continue to receive SC MK-6194 3 mg q4w in the extension period.
干预措施: MK-6194 (Biological)
结局指标
主要结局
Number of Participants Achieving Systemic Lupus Erythematosus Responder Index (SRI-4) Response at Week 28
时间窗: 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)
时间窗: 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
时间窗: 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.
次要结局
- Number of Participants Achieving British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response at Week 28(Week 28)
- Number of Participants Achieving SRI-4 Response at Week 52(Week 52)
- Number of Participants Achieving BICLA Response at Week 52(Week 52)
- Number of Participants With a Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-50 Response at Week 28(Week 28)
- Number of Participants With a CLASI-50 Response at Week 52(Week 52)
- Change From Baseline in Swollen Joint Count at Week 28(Baseline and Week 28)
- Change From Baseline in Swollen Joint Count at Week 52(Baseline and Week 52)
- Change From Baseline in Tender Joint Count at Week 28(Baseline and Week 28)
- Change From Baseline in Tender Joint Count at Week 52(Baseline and Week 52)
- Change From Baseline in Swollen and Tender Joint Count at Week 28(Baseline and Week 28)
- Change From Baseline in Swollen and Tender Joint Count at Week 52(Baseline and Week 52)
- Change From Baseline in Oral Corticosteroid Dose at Week 28(Baseline and Week 28)
- Change From Baseline in Oral Corticosteroid Dose at Week 52(Baseline and Week 52)
- Cumulative Oral Corticosteroid Use Between Week 0 and Week 28(Up to approximately 28 weeks)
- Cumulative Oral Corticosteroid Use Between Week 0 and Week 52(Up to approximately 52 weeks)
- Number of Participants Who Achieved Low Level of Disease Activity (LLDAS) at Week 28(Week 28)
- Number of Participants Who Achieved LLDAS at Week 52(Week 52)