Efficacy And Safety Of MK-6194 In Adult Participants With Systemic Lupus Erythematosus (MK-6194-006)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of MK-6194 in adult participants with Systemic Lupus Erythematosus. The primary hypothesis is that at least 1 of the MK-6194 arms is superior to placebo in the primary endpoint of percentage of participants with systemic lupus erythematosus responder index (SRI-4) response at Week 28.

Official Title
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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

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Biological: MK-6194
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 + antinuclear antibody (+ANA) (titer ≥1:80) or positive anti-double-strand deoxyribonucleic acid (dsDNA) antibody or positive anti-Sm antibody, or positive anti-SSA/Ro antibody. Has the presence of at least one of the following manifestations of SLE: Active lupus rash with 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: Has a concurrent clinically significant disease or clinically relevant laboratory abnormalities, or a history of any illness or medical condition that, in the opinion of the investigator, 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 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 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 clinically significant infection, or any infection requiring hospitalization or treatment with anti-infectives. Has evidence of active tuberculosis (TB), latent TB, or inadequately treated TB. Has confirmed or suspected 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 NSAID (excluding low-dose aspirin [<350 mg/day]) or is taking daily oral nonsteroidal anti-inflammatory drug (NSAID) at greater than the maximum recommended dosage. Is currently on any chronic systemic (oral or IV) anti-infective therapy for chronic infection (such as pneumocystis, cytomegalovirus, herpes zoster, or atypical mycobacteria).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Base Study: Dose 1<br>Participants receive subcutaneous (SC) MK-6194 dose regimen 1. | Biological: MK-6194<br>* SC Injection<br>|
| Experimental: Base Study: Dose 2<br>Participants receive SC MK-6194 dose regimen 2. | Biological: MK-6194<br>* SC Injection<br>|
| Placebo Comparator: Base Study: Placebo<br>Participants receive an SC placebo regimen. | Biological: Placebo<br>* SC Injection<br>|
| Experimental: Extension: Dose 1<br>Participants receive SC MK-6194 dose regimen 1. Participants from the arms Base Study: Dose 1 or Base Study: Placebo may be enrolled in this arm after completing participation in their original arm. | Biological: MK-6194<br>* SC Injection<br>Biological: Placebo<br>* SC Injection<br>|
| Experimental: Extension: Dose 2<br>Participants receive SC MK-6194 regimen 2. Participants from the arms Base Study: Dose 2 or Base Study: Placebo may be enrolled in this arm after completing participation in their original arm. | Biological: MK-6194<br>* SC Injection<br>Biological: Placebo<br>* SC Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Systemic Lupus Erythematosus Responder Index (SRI-4) Response at Week 28 | The SRI is a composite index used to assess clinical improvement in participants with Systemic Lupus Erythematosus (SLE). The SRI-4 response evaluates global improvement, any significant worsening in unaffected organ systems, and improvements in disease activity, without compromise to the patient's overall condition. SRI-4 response is binary and is either achieved or not achieved by the participant, thus there is no associated score. | Week 28 | 
| Percentage of Participants Experiencing Adverse Events (AEs) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. | Up to approximately 28 weeks | 
| Percentage of Participants Discontinuing Study Treatment Due to an AE | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. | Up to approximately 28 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment Response (BICLA) at Week 28 | The BICLA response is a composite global measure of SLE disease activity. It distinguishes between partial and complete improvement in all body systems. BICLA response is binary and is either achieved or not achieved by the participant, thus there is no associated score. | Week 28 | 
| Percentage of Participants Achieving SRI-4 Response at Week 52 | The SRI is a composite index used to assess clinical improvement in patients with Systemic Lupus Erythematosus (SLE). The SRI-4 response evaluates global improvement, any significant worsening in unaffected organ systems, and improvements in disease activity, without compromise to the patient's overall condition. SRI-4 response is binary and is either achieved or not achieved by the participant, thus there is no associated score. | Week 52 | 
| Percentage of Participants Achieving BICLA at Week 52 | The BICLA response is a composite global measure of SLE disease activity. It distinguishes between partial and complete improvement in all body systems. BICLA response is binary and is either achieved or not achieved by the participant, thus there is no associated score. | Week 52 | 
| Percentage of Participants with a Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-50 Response at Week 28 | The CLASI-A score is used to evaluate lupus skin manifestations. CLASI-A scores of 0 to 9, 10 to 20, and 21 to 70 represent disease severity of mild, moderate, and severe, respectively. CLASI-50 is 50% of improvement from baseline in the CLASI-A score. | Week 28 | 
| Percentage of Participants with a CLASI-50 Response at Week 52 | The CLASI-A score is used to evaluate lupus skin manifestations. CLASI-A scores of 0 to 9, 10 to 20, and 21 to 70 represent disease severity of mild, moderate, and severe, respectively. CLASI-50 is 50% of improvement from baseline in the CLASI-A score. | Week 52 | 
| Change From Baseline of 28 Joint Count at Week 28 | The joint count score is an evaluation of 28 joints in which joints are assessed for presence or absence of swelling and presence or absence of tenderness. The number of affected joints may range from 0 to 28; with higher values corresponding to higher disease activity and lower values to better. | Baseline and Week 28 | 
| Change From Baseline of 28 Joint Count at Week 52 | The joint count score is an evaluation of 28 joints in which joints are assessed for presence or absence of swelling and presence or absence of tenderness. The number of affected joints may range from 0 to 28; with higher values corresponding to higher disease activity and lower values to better. | Baseline and Week 52 | 
| Change From Baseline of Corticosteroid Dose at Week 28 | Participants are assessed for corticosteroid dose change. | Baseline and Week 28 | 
| Change From Baseline of Corticosteroid Dose at Week 52 | Participants are assessed for corticosteroid dose change. | Baseline and Week 52 | 
| Cumulative Oral Corticosteroid Use Between Week 0 to Week 28 | Participants are assessed for total corticosteroid use. | Up to approximately 28 weeks | 
| Cumulative Oral Corticosteroid Use Between Week 0 to Week 52 | Participants are assessed for total corticosteroid use. | Up to approximately 52 weeks | 
| Percentage of Participants Who Achieve Low Level of Disease Activity (LLDAS) at Week 28 | LLDAS is a low disease activity state associated with significant protection against flares and organ damage accrual. It includes both the measurement of disease activity and maintenance of immunosuppressive medications. LLDAS response is binary and is either achieved or not achieved by the participant, thus there is no associated score. | Week 28 | 
| Percentage of Participants Who Achieve LLDAS at Week 52 | LLDAS is a low disease activity state associated with significant protection against flares and organ damage accrual. It includes both the measurement of disease activity and maintenance of immunosuppressive medications. LLDAS response is binary and is either achieved or not achieved by the participant, thus there is no associated score. | Week 52 |