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Systemic Lupus ErythematosusPhase 1NCT04647708

Study of M5049 in CLE and SLE Participants

A Phase 1 study testing M5049 in people with Systemic Lupus Erythematosus and Cutaneous Lupus Erythematosus, run by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany at 12 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study is to evaluate the safety, tolerability and pharmacokinetics (PK) of orally administered M5049 in participants with systemic lupus erythematosus (SLE) or cutaneous lupus erythematosus (CLE). Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
M5049
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
25 participants
Where
12 sitesin 6 countries
Study dates
16 Dec 2020to 19 Dec 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Active systemic lupus erythematosus (SLE) with a Cutaneous lupus erythematosus disease area and activity index (CLASI-A) greater than or equal to [>= ] 6 and/or at least one active SLE clinical manifestation according to Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
  • Active cutaneous lupus erythematosus (CLE) (subacute cutaneous lupus erythematosus and/or discoid lupus erythematosus) with a CLASI-A >= 6
  • Other protocol defined inclusion criteria could apply

Who cannot join

  • Autoimmune or rheumatic disease other than SLE or CLE
  • Dermatological diseases other than cutaneous manifestations of SLE or CLE
  • Uncontrolled medical conditions including significant cardiovascular events, active lupus nephritis, and active neurological disorder
  • Ongoing or active clinically significant viral, bacterial or fungal infection
  • History of uncontrolled seizures or other neurological disorder
  • History of or positive for human immunodeficiency virus, hepatitis C virus, or hepatitis B virus
  • History of malignancy
  • Other protocol defined exclusion criteria could apply

Trial locations and contacts

12 sites in 6 countries.

12 sites in 6 countries

Bulgaria4 sites

  • Medical center Medconsult Pleven OOD

    Pleven

  • Medical Center-1-Sevlievo EOOD

    Sevlievo

  • Military Medical Academy - MHAT - Sofia

    Sofia

  • UMHAT "Sv. Ivan Rilski", EAD

    Sofia

Other trials in Bulgaria

Spain3 sites

  • Hospital Universitario Nuestra Señora de Valme

    Seville

  • Hospital Universitario Virgen del Rocio

    Seville

  • Hospital Universitario Rio Hortega - Servicio de Medicina Interna

    Valladolid

Other trials in Spain

Germany2 sites

  • SocraTec R&D GmbH

    Erfurt

  • Fraunhofer ITMP (Fraunhofer Institute for Translational Medicine and Pharmacology)

    Frankfurt

Other trials in Germany

Moldova1 site

  • ARENSIA Exploratory Medicine Phase I Unit, Clinical Republican Hospital

    Chisinau

Other trials in Moldova

North Macedonia1 site

  • PHI University Clinic of Rheumatology Skopje

    Skopje

Other trials in North Macedonia

Ukraine1 site

  • Medical Center of Limited Liability Company "Harmoniya krasy", Department of clinical trials

    Kyiv

Other trials in Ukraine

About this study

Official title: A Phase Ib, Randomized, Double-blind, Placebo Controlled Study to Evaluate the Safety and Pharmacokinetics of Multiple Ascending Doses of M5049 Administered Orally in SLE and CLE Participants Treated With Standard of Care

This study is to evaluate the safety, tolerability and pharmacokinetics (PK) of orally administered M5049 in participants with systemic lupus erythematosus (SLE) or cutaneous lupus erythematosus (CLE).

Being tested
M5049, Placebo
Keywords
Lupus Erythematosus, Systemic, Lupus Erythematosus, Cutaneous, Autoimmune Diseases
Medical subject headings
Lupus Erythematosus, Systemic, Lupus Erythematosus, Cutaneous, Autoimmune Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • M5049Drug

    Participants will receive low oral dose of M5049, twice daily in Part A.

  • M5049Drug

    Participants will receive ascending oral dose of M5049, twice daily in Part A.

  • M5049Drug

    Participants will receive high oral dose of M5049, twice daily in Part B.

  • PlaceboDrug

    Participants will receive placebo matched to M5049.

Study groups in NCT04647708
Study groupRoleWhat they receive
Part A (Cohort 1): M5049 Dose AExperimentalNot described
Receives: Drug: M5049
Part A (Cohort 2): M5049 Dose BExperimentalNot described
Receives: Drug: M5049
Part A (Cohort 3): M5049 Dose CExperimentalNot described
Receives: Drug: M5049
Part A (Cohort 4): M5049 Dose DExperimentalNot described
Receives: Drug: M5049
Part A: PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo
Part B (Cohort 5): M5049 Dose EExperimentalNot described
Receives: Drug: M5049
Part B: PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A: Cohort 1 and 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Event of Special Interest (AESI), TEAEs Leading to Permanent Treatment Discontinuation and Treatment-Related TEAEs

    Measured: Up to Day 102

  2. Part A: Cohort 3 and 4; Part B: Cohort 5: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Event of Special Interest (AESI), TEAEs Leading to Permanent Treatment Discontinuation and Treatment-Related TEAEs

    Measured: Up to Day 186

  3. Part A: Cohort 1 and 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Based on Severity

    Measured: Up to Day 102

  4. Part A: Cohort 3 and 4; Part B: Cohort 5: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Based on Severity

    Measured: Up to Day 186

  5. Part A: Cohort 1 and 2: Number of Participants with Clinically Significant Changes from Baseline in Laboratory Parameters, Vital Signs, Electroencephalogram (EEG) and Electrocardiogram (ECG) Findings

    Measured: Up to Day 102

  6. Part A: Cohort 3 and 4; Part B: Cohort 5: Number of Participants with Clinically Significant Changes from Baseline in Laboratory Parameters, Vital Signs, Electroencephalogram (EEG) and Electrocardiogram (ECG) Findings

    Measured: Up to Day 186

  7. Part A: Cohort 1 and 2: Number of Participants with Confirmed Signs and Symptoms of Prodromal Seizure

    Measured: Up to Day 102

  8. Part A: Cohort 3 and 4; Part B: Cohort 5: Number of Participants with Confirmed Signs and Symptoms of Prodromal Seizure

    Measured: Up to Day 186

  9. Part A: Cohort 1 and 2: Number of Participants with Suicidal Behavior and Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)

    Measured: Up to Day 102

Secondary outcomes (18)

  1. Part A and Part B: Maximum Observed Plasma Concentration (Cmax) of M5049

    Measured: Pre-dose up to Day 85 for Cohort 1 and 2 of Part A, up to Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B

  2. Part A and Part B: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M5049

    Measured: Day 1 and Day 29

  3. Part A and Part B: Time to Reach Maximum Plasma Concentration (tmax) of M5049

    Measured: Pre-dose up to Day 85 for Cohort 1 and 2 of Part A, up to Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B

  4. Part A and Part B: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of M5049

    Measured: Pre-dose up to Day 85 for Cohort 1 and 2 of Part A, up to Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B

  5. Part A and Part B: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of M5049

    Measured: Day 1 and Day 29

  6. Part A and Part B: Accumulation Ratio for Maximum Observed Plasma Concentration (Racc Cmax) of M5049

    Measured: Pre-dose up to Day 85 for Cohort 1 and 2 of Part A, up to Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B

  7. Part A and Part B: Elimination Rate Constant (Lambda z) of M5049

    Measured: Day 1 and Day 29

  8. Part A and Part B: Apparent Terminal Half-life (t1/2) of M5049

    Measured: Day 1 and Day 29

  9. Part A and Part B: Area Under the Plasma Concentration-Time Curve From Time Zero to 12 Hours Post-Dose (AUC0-12h) of M5049

    Measured: Day 29

  10. Part A and Part B: Dose Normalized Area Under Plasma Concentration-Time Curve from Time Zero to 12 Hours Post-Dose (AUC0-12h/Dose) of M5049

    Measured: Day 29

  11. Part A and Part B: Total Body Clearance (CL/f) of M5049

    Measured: Day 1

  12. Part A and Part B: Apparent Volume of Distribution (Vz/f) of M5049

    Measured: Day 1

  13. Part A and Part B: Area Under Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of M5049

    Measured: Day 1

  14. Part A and Part B: Dose Normalized Area Under Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of M5049

    Measured: Day 1

  15. Part A and Part B: Change from Baseline in Cutaneous Lupus Erythematosus Disease Area and Activity Index (CLASI-A)

    Measured: Baseline (Day 1) through Day 85 for Cohort 1 and 2 of Part A, Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B

  16. Part A and Part B: Change from Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)

    Measured: Baseline (Day 1) through Day 85 for Cohort 1 and 2 of Part A, Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B

  17. Part A and Part B: Change from Baseline in 28-Joint Count

    Measured: Baseline (Day 1) through Day 85 for Cohort 1 and 2 of Part A, Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B

  18. Part A and Part B: Change from Baseline in Physician Global Assessment (PGA) Score

    Measured: Baseline (Day 1) through Day 85 for Cohort 1 and 2 of Part A, Day 169 for Cohort 3, 4 of Part A and Cohort 5 of Part B

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Dec 2020
  2. Study start16 Dec 2020
  3. Primary completion19 Dec 2023
  4. Study completion19 Dec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04647708
Sponsor's protocol ID
MS200569_0004
Other IDs
2020-003118-11
Status last verified
Feb 2024
First submitted
23 Nov 2020
Last updated
21 Feb 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://bit.ly/IPD21

Publications

  • Witte T, Fernandez-Ruiz R, Abramova N, Weinelt D, Moreau F, Klopp-Schulze L, Shaw J, Denis D, Wenzel J. Enpatoran, a first-in-class, selective, orally administered toll-like receptor 7/8 inhibitor, in systemic and cutaneous lupus erythematosus: results from a randomised, placebo-controlled phase Ib study. Lupus Sci Med. 2025 Oct 23;12(2):e001705. doi: 10.1136/lupus-2025-001705.

    PubMed 41136221

  • Klopp-Schulze L, Shaw JV, Dong JQ, Khandelwal A, Vazquez-Mateo C, Goteti K. Applying Modeling and Simulations for Rational Dose Selection of Novel Toll-Like Receptor 7/8 Inhibitor Enpatoran for Indications of High Medical Need. Clin Pharmacol Ther. 2022 Aug;112(2):297-306. doi: 10.1002/cpt.2606. Epub 2022 May 21.

    PubMed 35390178

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing M5049 in people with Systemic Lupus Erythematosus and Cutaneous Lupus Erythematosus, run by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany at 12 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Bulgaria, Spain, Germany, Moldova, North Macedonia and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Cohort 1 and 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Event of Special Interest (AESI), TEAEs Leading to Permanent Treatment Discontinuation and Treatment-Related TEAEs (time frame: Up to Day 102). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04647708, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2024.

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