Lupus Erythematosus, SystemicPhase 1NCT02537028
MSC2364447C Phase 1b in Systemic Lupus Erythematosus
A Phase 1 study testing MSC2364447C in people with Lupus Erythematosus, Systemic, run by EMD Serono Research & Development Institute, Inc. at 13 sites in 2 countries.
Trial summary
The primary purpose of this Phase 1b double-blind, randomized, placebo-controlled trial is to evaluate the safety, tolerability, pharmacokinetic (PK), and biological effect of MSC2364447C administered for 4 weeks in systemic lupus erythematosus subjects (SLE). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Lupus Erythematosus, Systemic
- What is being tested?
- MSC2364447C
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 13 sitesin 2 countries
- Study dates
- 30 Nov 2015to 4 Oct 2016
- 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
- Male or female of 18 to 65 years of age
- Diagnosis of systemic lupus erythematosus (SLE) (at least 4 of the 11 American College of Rheumatology [ACR] classification criteria for SLE) of at least 6 months duration at the Screening visit
- Positive test results for anti-nuclear antibody (ANA) (human epithelial cell-2 ANA greater than or equal to [>=] 1:80) and/or anti-dsDNA antibody (>= 30 international units per milliliter [IU/mL]) at the Screening visit
- At least 1 SLE disease manifestation (assessed by Systemic Lupus Erythematosus Disease Activity Index-2000 [SLEDAI-2K]) other than positive antidsDNA and no central nervous system (CNS) SLE (psychosis, organic brain syndrome, cranial nerve disorder, lupus headache, or new-onset cerebrovascular accident)
- History of vaccinations as follows or vaccination against these pathogens during Screening:
- Vaccination against Streptococcus pneumoniae with pneumococcal polysaccharide vaccine 23 or pneumococcal 13-valent conjugate vaccine as per local guidelines, and
- Vaccination against influenza virus (as per local seasonal recommendations). Subjects receiving 1 or more of these vaccinations during screening must have at least 2 weeks between the vaccination(s) and the date of randomization at Day 1.
- Other protocol defined inclusion criteria could apply
Who cannot join
- Active clinically significant CNS SLE
- Initiation or change in dose of anti-malarial treatment after the screening visit
- Within 2 weeks prior to Screening or during Screening: use of oral corticosteroids greater than (>) 40 mg daily prednisone equivalent, use of any injectable corticosteroids, or change in dose of corticosteroids
- Within 2 weeks prior to Screening, initiation or change in dose of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, or nonsteroidal anti-inflammatory drugs (NSAIDs).
- Within 2 months prior to Screening or during Screening: initiation of or change in dose of methotrexate, mycophenolate (mofetil or sodium), or azathioprine
- Within 2 months prior to Screening or during Screening, use of cyclosporine, tacrolimus, leflunomide, abatacept, anti-tumor necrosis factor alpha agents, intravenous immunoglobulin, plasmapheresis, or other disease-modifying, immunosuppressive, or immunomodulatory therapies not otherwise specified in protocol
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- Within 6 months prior to Screening or during Screening: use of cyclophosphamide or chlorambucil
- Within 12 months prior to screening or during screening: use of rituximab, belimumab, or any other B cell-depleting or modulating therapies
- Within 1 month prior to Screening or during Screening, vaccination with live or live-attenuated virus vaccine.
- Active clinically significant viral, bacterial or fungal infection, or any serious episode of infection requiring hospitalization within the last 6 months - Estimated glomerular filtration rate by the Modification of Diet in Renal Disease equation of less than (<) 60 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2), or recent decline in kidney function, or proteinuria >= 3 gram per day (g/day) (spot urine protein/creatinine ratio >= 3 mg/mg)
- Other protocol defined exclusion criteria could apply
Trial locations and contacts
13 sites in 2 countries.
13 sites in 2 countries
United States10 sites
Research site
Anniston, Alabama, 36207
Research site
Austin, Texas, 78745
Research site
Clearwater, Florida, 33765
Research site
DeBary, Florida, 32713
Research site
El Cajon, California, 92020-4124
Research site
Grand Blanc, Michigan, 48439
Research site
Lakewood, California, 90712
Research site
Los Angeles, California, 90048
Research site
Orlando, Florida, 32806
Research site
St Louis, Missouri, 63117
Bulgaria3 sites
Research site
Sofia, 1336
Research site
Sofia, 1431
Research site
Sofia, 1612
About this study
Official title: A Phase Ib Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Biological Effect of MSC2364447C in Systemic Lupus Erythematosus
The primary purpose of this Phase 1b double-blind, randomized, placebo-controlled trial is to evaluate the safety, tolerability, pharmacokinetic (PK), and biological effect of MSC2364447C administered for 4 weeks in systemic lupus erythematosus subjects (SLE).
- Conditions
- Lupus Erythematosus, Systemic
- Being tested
- MSC2364447C, Placebo
- Keywords
- MSC2364447C, Phase 1, BTK inhibitor, Systemic Lupus Erythematosus, M2951, Lupus
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MSC2364447CDrug
Also called M2951, Evobrutinib
Subjects will be administered with MSC2364447C 25 milligrams orally once daily for 4 weeks.
MSC2364447CDrug
Also called M2951, Evobrutinib
Subjects will be administered with MSC2364447C 75 milligrams orally once daily for 4 weeks.
PlaceboDrug
Subjects will be administered with placebo matching to MSC2364447C orally once daily for 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| MSC2364447C 25 mg | Experimental | Not described Receives: Drug: MSC2364447C |
| MSC2364447C 75 mg | Experimental | Not described Receives: Drug: MSC2364447C |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects with treatment emergent adverse events (TEAEs)
TEAEs will be defined as the adverse events (AEs) that occur between first dose of study drug administration up to 4 weeks after the last dose of study drug administration that were absent before treatment or that worsened relative to pretreatment state.
Measured: From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
Number of subjects with TEAEs according to severity
The severity of TEAEs will be graded using National cancer institute-Common Terminology Criteria for Adverse Events version 4.03 (NCI-CTCAE v 4.03) definitions of Grade 1 through Grade 5 following his/her best medical judgment. The severity of the AEs will be classified as follows: Grade 1 or mild, Grade 2 or moderate, Grade 3 or severe, Grade 4 or life-threatening and Grade 5 or death.
Measured: From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
Number of subjects with clinically significant laboratory abnormalities
Clinical laboratory parameters being monitored for safety will be summarized using descriptive statistics, by postdose shifts relative to Baseline for relevant parameters using relevant cut-offs. Clinical significance will be determined by investigator.
Measured: screening up to Day 56
Number of subjects with clinically significant abnormal vital signs: blood pressure, pulse rate, respiratory rate
Observed values and changes from Baseline in vital signs will be summarized for each treatment group using descriptive statistics. Clinically noteworthy changes in vital signs will be listed and summarized as appropriate. A semi-automated blood pressure and pulse rate recording device with an appropriate cuff size will be utilized. Blood pressure and pulse rate will be measured after 10 minutes' rest in the semi-supine position with the subject's arm unconstrained by clothing or other material. The blood pressure should be assessed on the same arm for each subject throughout the trial. Clinical significance will be determined by investigator.
Measured: screening up to Day 56
Number of subjects with clinically significant abnormal electrocardiograms (ECGs)
Observed values and changes from Baseline in ECG will be summarized for each treatment group using descriptive statistics. Clinically noteworthy changes in ECG will be listed and summarized as appropriate. Clinical significance will be determined by investigator.
Measured: screening up to Day 28
Secondary outcomes (8)
Area under the plasma concentration-time curve from time zero to 6 hours after administration (AUC0-6)
Measured: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Maximum observed plasma concentration (Cmax)
Measured: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Time to reach maximum plasma concentration (tmax)
Measured: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Concentration observed immediately before next dosing (Cpre) (Day 28)
Measured: Predose (within 30 minutes prior to dosing) on Day 28
Dose-normalized AUC0-6h (AUC0-6h/dose)
Measured: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Dose-normalized Cmax (Cmax/dose)
Measured: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Accumulation ratio for AUC0-6 (Racc(AUC0-6))
Accumulation ratio for AUC will be calculated as AUC0-6, Day28 divided by AUC0-6, Day1
Measured: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Accumulation ratio for Cmax (Racc(Cmax))
Accumulation ratio for Cmax, calculated as Cmax, Day28 divided by Cmax, Day1
Measured: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2015 (estimated)
- Study start30 Nov 2015
- Primary completion4 Oct 2016
- Study completion4 Oct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lupus Erythematosus, SystemicStudies of the same condition, open and under way.
- More trials run by EMD Serono Research & Development Institute, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, EMD Serono Research & Development Institute, Inc., a business of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02537028
- Sponsor's protocol ID
- EMR200527-002
- Other IDs
- 2015-001891-23, 2015
- Status last verified
- Oct 2017
- First submitted
- 28 Aug 2015
- Last updated
- 9 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Biological Effect of MSC2364447C in Systemic Lupus Erythematosus
- ClinicalTrials.gov ID
- NCT02537028
- Acronym / sponsor ID
- EMR200527-002
- Conditions
- Lupus Erythematosus, Systemic
- Keywords
- MSC2364447C, Phase 1, BTK inhibitor, Systemic Lupus Erythematosus, M2951, Lupus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- EMD Serono Research & Development Institute, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Study start
- 30 Nov 2015 (actual)
- Primary completion
- 4 Oct 2016 (actual)
- Study completion
- 4 Oct 2016 (actual)
- First posted
- 1 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this Phase 1b double-blind, randomized, placebo-controlled trial is to evaluate the safety, tolerability, pharmacokinetic (PK), and biological effect of MSC2364447C administered for 4 weeks in systemic lupus erythematosus subjects (SLE).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MSC2364447C 25 mg | Experimental | Drug: MSC2364447C |
| MSC2364447C 75 mg | Experimental | Drug: MSC2364447C |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female of 18 to 65 years of age
- Diagnosis of systemic lupus erythematosus (SLE) (at least 4 of the 11 American College of Rheumatology [ACR] classification criteria for SLE) of at least 6 months duration at the Screening visit
- Positive test results for anti-nuclear antibody (ANA) (human epithelial cell-2 ANA greater than or equal to [>=] 1:80) and/or anti-dsDNA antibody (>= 30 international units per milliliter [IU/mL]) at the Screening visit
- At least 1 SLE disease manifestation (assessed by Systemic Lupus Erythematosus Disease Activity Index-2000 [SLEDAI-2K]) other than positive antidsDNA and no central nervous system (CNS) SLE (psychosis, organic brain syndrome, cranial nerve disorder, lupus headache, or new-onset cerebrovascular accident)
- History of vaccinations as follows or vaccination against these pathogens during Screening:
Key exclusion criteria (11 listed)
- Active clinically significant CNS SLE
- Initiation or change in dose of anti-malarial treatment after the screening visit
- Within 2 weeks prior to Screening or during Screening: use of oral corticosteroids greater than (>) 40 mg daily prednisone equivalent, use of any injectable corticosteroids, or change in dose of corticosteroids
- Within 2 weeks prior to Screening, initiation or change in dose of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, or nonsteroidal anti-inflammatory drugs (NSAIDs).
- Within 2 months prior to Screening or during Screening: initiation of or change in dose of methotrexate, mycophenolate (mofetil or sodium), or azathioprine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MSC2364447CAlso: M2951, EvobrutinibSubjects will be administered with MSC2364447C 25 milligrams orally once daily for 4 weeks. | Drug | MSC2364447C 25 mg |
| MSC2364447CAlso: M2951, EvobrutinibSubjects will be administered with MSC2364447C 75 milligrams orally once daily for 4 weeks. | Drug | MSC2364447C 75 mg |
| PlaceboSubjects will be administered with placebo matching to MSC2364447C orally once daily for 4 weeks. | Drug | Placebo |
Primary outcome
Number of subjects with treatment emergent adverse events (TEAEs)
Time frame: From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
TEAEs will be defined as the adverse events (AEs) that occur between first dose of study drug administration up to 4 weeks after the last dose of study drug administration that were absent before treatment or that worsened relative to pretreatment state.
Number of subjects with TEAEs according to severity
Time frame: From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
The severity of TEAEs will be graded using National cancer institute-Common Terminology Criteria for Adverse Events version 4.03 (NCI-CTCAE v 4.03) definitions of Grade 1 through Grade 5 following his/her best medical judgment. The severity of the AEs will be classified as follows: Grade 1 or mild, Grade 2 or moderate, Grade 3 or severe, Grade 4 or life-threatening and Grade 5 or death.
Number of subjects with clinically significant laboratory abnormalities
Time frame: screening up to Day 56
Clinical laboratory parameters being monitored for safety will be summarized using descriptive statistics, by postdose shifts relative to Baseline for relevant parameters using relevant cut-offs. Clinical significance will be determined by investigator.
Number of subjects with clinically significant abnormal vital signs: blood pressure, pulse rate, respiratory rate
Time frame: screening up to Day 56
Observed values and changes from Baseline in vital signs will be summarized for each treatment group using descriptive statistics. Clinically noteworthy changes in vital signs will be listed and summarized as appropriate. A semi-automated blood pressure and pulse rate recording device with an appropriate cuff size will be utilized. Blood pressure and pulse rate will be measured after 10 minutes' rest in the semi-supine position with the subject's arm unconstrained by clothing or other material. The blood pressure should be assessed on the same arm for each subject throughout the trial. Clinical significance will be determined by investigator.
Number of subjects with clinically significant abnormal electrocardiograms (ECGs)
Time frame: screening up to Day 28
Observed values and changes from Baseline in ECG will be summarized for each treatment group using descriptive statistics. Clinically noteworthy changes in ECG will be listed and summarized as appropriate. Clinical significance will be determined by investigator.
8 secondary outcomes
Area under the plasma concentration-time curve from time zero to 6 hours after administration (AUC0-6)
Time frame: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Maximum observed plasma concentration (Cmax)
Time frame: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Time to reach maximum plasma concentration (tmax)
Time frame: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Concentration observed immediately before next dosing (Cpre) (Day 28)
Time frame: Predose (within 30 minutes prior to dosing) on Day 28
Dose-normalized AUC0-6h (AUC0-6h/dose)
Time frame: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Dose-normalized Cmax (Cmax/dose)
Time frame: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Accumulation ratio for AUC0-6 (Racc(AUC0-6))
Time frame: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Accumulation ratio for Cmax (Racc(Cmax))
Time frame: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
EMD Serono Research & Development Institute, Inc., a business of Merck KGaA, Darmstadt, Germany
13 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MSC2364447C in people with Lupus Erythematosus, Systemic, run by EMD Serono Research & Development Institute, Inc. at 13 sites in 2 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 8 inclusion and 11 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 9 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Bulgaria. 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?
Number of subjects with treatment emergent adverse events (TEAEs) (time frame: From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Oct 2017.