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

• ClinicalTrials.gov Identifier: NCT06161116
• Recruitment Status: Recruiting
• First Posted: December 7, 2023
• Last Update Posted: May 10, 2024
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: November 29, 2023
• First Posted Date: December 7, 2023
• Last Update Posted Date: May 10, 2024
• Actual Study Start Date: December 27, 2023
• Estimated Primary Completion Date: January 22, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 14, 2023)

• Percentage of Participants Achieving Systemic Lupus Erythematosus Responder Index (SRI-4) Response at Week 28 [ Time Frame: 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.
• Percentage of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to approximately 28 weeks ]
  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.
• Percentage of Participants Discontinuing Study Treatment Due to an AE [ Time Frame: Up to approximately 28 weeks ]
  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.

Original Primary Outcome Measures (submitted: November 29, 2023)

• Percentage of Participants Achieving Systemic Lupus Erythematosus Responder Index (SRI-4) Response at Week 28 [ Time Frame: 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.
• Percentage of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to approximately 28 weeks ]
  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.
• Percentage of Participants Discontinuing Study Treatment Due to an AE [ Time Frame: Up to approximately 28 weeks ]
  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.

Current Secondary Outcome Measures (submitted: December 14, 2023)

• Percentage of Participants Achieving British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment Response (BICLA) at Week 28 [ Time Frame: 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.
• Percentage of Participants Achieving SRI-4 Response at Week 52 [ Time Frame: 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.
• Percentage of Participants Achieving BICLA at Week 52 [ Time Frame: 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.
• Percentage of Participants with a Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-50 Response at Week 28 [ Time Frame: 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.
• Percentage of Participants with a CLASI-50 Response at Week 52 [ Time Frame: 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.
• Change From Baseline of 28 Joint Count at Week 28 [ Time Frame: Baseline and 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.
• Change From Baseline of 28 Joint Count at Week 52 [ Time Frame: Baseline and 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.
• Change From Baseline of Corticosteroid Dose at Week 28 [ Time Frame: Baseline and Week 28 ]
  Participants are assessed for corticosteroid dose change.
• Change From Baseline of Corticosteroid Dose at Week 52 [ Time Frame: Baseline and Week 52 ]
  Participants are assessed for corticosteroid dose change.
• Cumulative Oral Corticosteroid Use Between Week 0 to Week 28 [ Time Frame: Up to approximately 28 weeks ]
  Participants are assessed for total corticosteroid use.
• Cumulative Oral Corticosteroid Use Between Week 0 to Week 52 [ Time Frame: Up to approximately 52 weeks ]
  Participants are assessed for total corticosteroid use.
• Percentage of Participants Who Achieve Low Level of Disease Activity (LLDAS) at Week 28 [ Time Frame: 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.
• Percentage of Participants Who Achieve LLDAS at Week 52 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: November 29, 2023)

• Percentage of Participants Achieving British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment Response (BICLA) at Week 28 [ Time Frame: 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.
• Percentage of Participants Achieving SRI-4 Response at Week 52 [ Time Frame: 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.
• Percentage of Participants Achieving BICLA at Week 52 [ Time Frame: 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.
• Percentage of Participants with a Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-50 Response at Week 28 [ Time Frame: 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.
• Percentage of Participants with a CLASI-50 Response at Week 52 [ Time Frame: 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.
• Change From Baseline of 28 Joint Count at Week 28 [ Time Frame: Baseline and 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.
• Change From Baseline of 28 Joint Count at Week 52 [ Time Frame: Baseline and 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.
• Change From Baseline of Corticosteroid Dose at Week 28 [ Time Frame: Baseline and Week 28 ]
  Participants are assessed for corticosteroid dose change.
• Change From Baseline of Corticosteroid Dose at Week 52 [ Time Frame: Baseline and Week 52 ]
  Participants are assessed for corticosteroid dose change.
• Cumulative Oral Corticosteroid Use Between Week 0 to Week 28 [ Time Frame: Up to approximately 28 weeks ]
  Participants are assessed for total corticosteroid use.
• Cumulative Oral Corticosteroid Use Between Week 0 to Week 52 [ Time Frame: Up to approximately 52 weeks ]
  Participants are assessed for total corticosteroid use.
• Percentage of Participants Who Achieve Low Level of Disease Activity (LLDAS) at Week 28 [ Time Frame: 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.
• Percentage of Participants Who Achieve LLDAS at Week 52 [ Time Frame: 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy And Safety Of MK-6194 In Adult Participants With Systemic Lupus Erythematosus (MK-6194-006)
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Systemic Lupus Erythematosus

Intervention

• Biological: MK-6194
  SC Injection
• Biological: Placebo
  SC Injection

Study Arms

• Experimental: Base Study: Dose 1
  Participants receive subcutaneous (SC) MK-6194 dose regimen 1.
  Intervention: Biological: MK-6194
• Experimental: Base Study: Dose 2
  Participants receive SC MK-6194 dose regimen 2.
  Intervention: Biological: MK-6194
• Placebo Comparator: Base Study: Placebo
  Participants receive an SC placebo regimen.
  Intervention: Biological: Placebo
• Experimental: Extension: Dose 1
  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.
  Interventions:

  • Biological: MK-6194
  • Biological: Placebo
• Experimental: Extension: Dose 2
  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.
  Interventions:

  • Biological: MK-6194
  • Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 29, 2023): 270
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 9, 2027
• Estimated Primary Completion Date: January 22, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 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 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 active infection (such as pneumocystis, cytomegalovirus, herpes zoster, or atypical mycobacteria).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Toll Free Number; 1-888-577-8839; Trialsites@merck.com

• Listed Location Countries: Canada, Chile, France, Guatemala, Italy, Japan, Poland, Spain, United States

Administrative Information

• NCT Number: NCT06161116
• Other Study ID Numbers: 6194-006; MK-6194-006 ( Other Identifier: Merck ); 2023-505520-61 ( Registry Identifier: EU CT ); U1111-1291-8716 ( Other Identifier: UTN ); jRCT2041230137 ( Registry Identifier: jRCT )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: May 2024