A clinical study of MK-6194 for the treatment of Systemic Lupus Erythematosus (SLE) (MK-6194-006)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

11 Mar 2024 → 30 Jul 2025

Decision date (initial)

2024-02-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-505520-61-00

WHO UTN

U1111-1291-8716

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety, Pharmacodynamic, Pharmacogenetic, Therapy, Pharmacogenomic

1. To evaluate the efficacy of MK-6194 compared to placebo as assessed by the proportion of participants with SRI-4 response at Week 28.
2. To evaluate the safety and tolerability of MK-6194.

Secondary objectives 8

1. To evaluate the efficacy of MK-6194 compared to placebo as assessed by the proportion of participants with BICLA response at Week 28.
2. To evaluate the efficacy of MK-6194 compared to placebo as assessed by the proportion of participants with SRI-4 response at Week 52.
3. To evaluate the efficacy of MK-6194 compared to placebo as assessed by the proportion of participants with BICLA response at Week 52.
4. To evaluate the efficacy of MK-6194 compared to placebo as assessed by the proportion of participants with a CLASI activity score ≥8 at baseline achieving a CLASI-50 response at Weeks 28 and 52, respectively.
5. To evaluate the efficacy of MK-6194 compared to placebo as assessed by the change from baseline on 28 joint count in participants with ≥3 swollen joints at baseline, participants with ≥3 tender joints at baseline, and ≥3 tender and swollen joints at baseline at Weeks 28 and 2, respectively.
6. To evaluate the efficacy of MK-6194 compared to placebo as assessed by the change from baseline in corticosteroid dose at Weeks 28 and 52, respectively.
7. To evaluate the efficacy of MK-6194 compared to placebo as assessed by cumulative oral corticosteroid use at Weeks 28 and 52, respectively.
8. To evaluate the efficacy of MK-6194 compared to placebo as assessed by the proportion of participants who achieve LLDAS at Week 28 and Week 52, respectively.

Conditions and MedDRA coding

Systemic Lupus Erythematosus

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Has a diagnosis of systemic lupus erythematosus (SLE) ≥6 months prior to Screening.
2. Is taking at least 1 background therapy (1 immunosuppressant or dapsone and/or 1 antimalarial and/or oral corticosteroids) for SLE.
3. 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
4. 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).
5. Has a hybrid Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) total score of ≥6 and clinical hybrid SLEDAI score of ≥4.

Exclusion criteria 17

1. 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.
2. 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.
3. Has a severe chronic pulmonary disease requiring oxygen therapy.
4. Has a transplanted organ which requires continued immunosuppression.
5. Has a known systemic hypersensitivity to IL-2, or modified IL-2 including MK-6194, or its inactive ingredients.
6. Has a known history of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly.
7. Has drug-induced cutaneous lupus erythematosus (CLE) and/or drug-induced SLE in the setting of continued treatment with a causative agent.
8. 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.
9. Has a diagnosis of Antiphospholipid Syndrome with history of vascular thrombosis, catastrophic APS, or pregnancy morbidity within 6 months prior to Screening.
10. Has a history of any malignancy, except for successfully treated non-melanoma skin cancer or localized carcinoma in situ of the cervix.
11. Has an active or clinically significant infection, requiring hospitalization or treatment with anti-infectives.
12. Has evidence of active tuberculosis (TB), latent TB, or inadequately treated TB.
13. Has confirmed or suspected COVID-19 infection.
14. Has had major surgery within 3 months prior to Screening or has a major surgery planned during the study.
15. Is taking more than 1 immunosuppressant.
16. 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.
17. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Percentage of Participants Achieving Systemic Lupus Erythematosus Responder Index (SRI-4) Response at Week 28
2. Percentage of Participants Experiencing Adverse Events (AEs)
3. Percentage of Participants Discontinuing Study Treatment Due to an AE

Secondary endpoints 13

1. Percentage of Participants Achieving British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment Response (BICLA) at Week 28
2. Percentage of Participants Achieving SRI-4 Response at Week 52
3. Percentage of Participants Achieving BICLA at Week 52
4. Percentage of Participants with a Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-50 Response at Week 28
5. Percentage of Participants with a CLASI-50 Response at Week 52
6. Change From Baseline of 28 Joint Count at Week 28
7. Change From Baseline of 28 Joint Count at Week 52
8. Change From Baseline of Corticosteroid Dose at Week 28
9. Change From Baseline of Corticosteroid Dose at Week 52
10. Cumulative Oral Corticosteroid Use Between Week 0 to Week 28
11. Cumulative Oral Corticosteroid Use Between Week 0 to Week 52
12. Percentage of Participants Who Achieve Low Level of Disease Activity (LLDAS) at Week 28
13. Percentage of Participants Who Achieve LLDAS at Week 52

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Nancy Kim

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Nancy Kim

Third parties 5

Locations

4 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 57 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications