Clinical trial NCT02537028: MSC2364447C Phase 1b in Systemic Lupus Erythematosus
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lupus Erythematosus, Systemic
Keywords: MSC2364447C
Phase 1
BTK inhibitor
Systemic Lupus Erythematosus
M2951
Lupus
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2015-09-01
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: Inclusion Criteria:

* 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:

  1. Vaccination against Streptococcus pneumoniae with pneumococcal polysaccharide vaccine 23 or pneumococcal 13-valent conjugate vaccine as per local guidelines, and
  2. 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

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Number of subjects with treatment emergent adverse events (TEAEs)
timeFrame: From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
measure: Number of subjects with TEAEs according to severity
timeFrame: From the first dose of study drug administration up to 4 weeks after the last dose of study drug administration
measure: Number of subjects with clinically significant laboratory abnormalities
timeFrame: screening up to Day 56
measure: Number of subjects with clinically significant abnormal vital signs: blood pressure, pulse rate, respiratory rate
timeFrame: screening up to Day 56
measure: Number of subjects with clinically significant abnormal electrocardiograms (ECGs)
timeFrame: screening up to Day 28
Secondary outcomes:
measure: Area under the plasma concentration-time curve from time zero to 6 hours after administration (AUC0-6)
timeFrame: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
measure: Time to reach maximum plasma concentration (tmax)
timeFrame: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
measure: Concentration observed immediately before next dosing (Cpre) (Day 28)
timeFrame: Predose (within 30 minutes prior to dosing) on Day 28
measure: Dose-normalized AUC0-6h (AUC0-6h/dose)
timeFrame: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
measure: Dose-normalized Cmax (Cmax/dose)
timeFrame: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
measure: Accumulation ratio for AUC0-6 (Racc(AUC0-6))
timeFrame: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
measure: Accumulation ratio for Cmax (Racc(Cmax))
timeFrame: Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Research site
state: Alabama
city: El Cajon
country: United States
facility: Research site
state: California
city: Lakewood
country: United States
facility: Research site
state: California
city: Los Angeles
country: United States
facility: Research site
state: California
city: Clearwater
country: United States
facility: Research site
state: Florida
city: DeBary
country: United States
facility: Research site
state: Florida
city: Orlando
country: United States
facility: Research site
state: Florida
city: Grand Blanc
country: United States
facility: Research site
state: Michigan
city: Saint Louis
country: United States
facility: Research site
state: Missouri
city: Austin
country: United States
facility: Research site
state: Texas
city: Sofia
country: Bulgaria
facility: Research site
city: Sofia
country: Bulgaria
facility: Research site
city: Sofia
country: Bulgaria
facility: Research site
Study officials:
affiliation: EMD Serono Research & Development Institute, Inc., a business of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: