MSC2364447C Phase 1b in Systemic Lupus Erythematosus

NCT02537028 | Completed Phase 1 DMC

• 2 other identifiers: EMR200527-0022015-001891-23
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 13

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).

Conditions

Lupus Erythematosus, Systemic

Keywords

MSC2364447C; Phase 1; BTK inhibitor; Systemic Lupus Erythematosus; M2951; Lupus

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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.

  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.

  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)

  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)

  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)

  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)

  Predose (within 30 minutes prior to dosing) on Day 28

• Dose-normalized AUC0-6h (AUC0-6h/dose)

  Predose, 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 hours post-dose on Day 1 and Day 28

Study Arms (3)

MSC2364447C 25 mg

EXPERIMENTAL

Drug: MSC2364447C

MSC2364447C 75 mg

EXPERIMENTAL

Drug: MSC2364447C

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

MSC2364447C DRUG

Subjects will be administered with MSC2364447C 25 milligrams orally once daily for 4 weeks.

Also known as: M2951, Evobrutinib

MSC2364447C 25 mg

Placebo DRUG

Subjects will be administered with placebo matching to MSC2364447C orally once daily for 4 weeks.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (13)

Research site

Anniston, Alabama, 36207, United States

Location

Research site

El Cajon, California, 92020-4124, United States

Location

Research site

Lakewood, California, 90712, United States

Location

Research site

Los Angeles, California, 90048, United States

Location

Research site

Clearwater, Florida, 33765, United States

Location

Research site

DeBary, Florida, 32713, United States

Location

Research site

Orlando, Florida, 32806, United States

Location

Research site

Grand Blanc, Michigan, 48439, United States

Location

Research site

St Louis, Missouri, 63117, United States

Location

Research site

Austin, Texas, 78745, United States

Location

Research site

Sofia, 1336, Bulgaria

Location

Research site

Sofia, 1431, Bulgaria

Location

Research site

Sofia, 1612, Bulgaria

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

evobrutinib

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Medical Responsible

  EMD Serono Research & Development Institute, Inc., a business of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2015
• First Posted: September 1, 2015
• Study Start: November 30, 2015
• Primary Completion: October 4, 2016
• Study Completion: October 4, 2016
• Last Updated: October 9, 2017

Record last verified: 2017-10

Locations

BU (3); US (10)