Clinical trial NCT01973491: ATX-MS-1467 in Multiple Sclerosis
Official title: An Open-label, One-arm, Proof of Concept Trial to Evaluate the Safety of ATX-MS-1467 (MSC2358825A) and Its Effect on Immune Tolerance in Subjects With Relapsing Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Sclerosis
Keywords: ATX-MS-1467 (MSC2358825A)
Relapsing Multiple Sclerosis
Magnetic resonance imaging (MRI)
M2736
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2013-10-31
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multi-center, open-label, single arm, baseline-controlled Phase 2a trial to evaluate the clinical and biological effects of ATX-MS-1467 in subjects with relapsing multiple sclerosis (MS) and to assess the maintenance of any such effects.


Eligibility criteria: Inclusion Criteria:

* Male or female out-patients aged 18 to 65 years of age inclusive at the time of informed consent
* Willing and able to provide written informed consent and to comply with the requirements of the protocol assessments/procedures
* Relapsing MS (relapsing-remitting multiple sclerosis \[RRMS\], secondary progressive multiple sclerosis \[SPMS\], as defined by the revised McDonald criteria \[2010\]) (11)
* Clinical evidence of recent MS activity and radiological activity on gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) defined as defined in the protocol
* Expanded disability status scale (EDSS) score 0-5.5
* Human leukocyte antigen-beta chain (HLA-DRB)1\*15 positive
* Neurological stability in the 30 days prior to Visit 5 (Study Day 1)
* Prior vaccination against tuberculosis (TB)
* If female, unless post-menopausal (for at least 2 years) or surgically sterilized, must be willing to use two highly effective methods of contraception throughout the entire duration of the trial and for 90 days following the last dose of ATX-MS-1467
* If male, must be willing to use two highly effective methods of contraception throughout the entire duration of the trial and for 90 days following the last dose of ATX-MS-1467

Exclusion Criteria:

* Primary progressive MS
* Inability to comply with MRI scanning, including contra-indications to MRI such as known allergy to gadolinium contrast dyes, claustrophobia, presence of a pacemaker, cochlear implants, ferromagnetic devices or clips, intracranial vascular clips, insulin pumps, nerve stimulators
* Previous treatment with beta-interferon, plasma exchange, intravenous gamma globulin within the 8 weeks prior to study Day 1 (Visit 5), steroids (administered via the oral and/or parenteral routes) or adrenocorticotropic hormone within the 30 days prior to the Visit 2 MRI scan, glatiramer acetate, cytotoxic agents
* Prior exposure to dimethyl fumurate (BG-12) or dirucotide, any disease-related T cell vaccine or peptide-tolerizing agent for the treatment of MS, including ATX-MS-1467
* Use of any investigational drug or experimental procedure for MS (including cytokine or anticytokine therapy) within the 30 days prior to screening (Visit 1)
* Inadequate liver function as defined in the protocol.
* Lymphocyte count less than (\<)500 per micro liter (/mcL) or neutrophil count \< 1500 mcL at screening or at any of the pre-treatment visits (Visits 2-4)
* Major medical illness as defined in the protocol
* Known history of active or chronic infectious disease or any disease which compromises immune function
* Any renal condition that would preclude the administration of gadolinium
* History of malignancy, including both solid tumor and hematological malignancies, but excluding basal cell and in situ squamous cell carcinomas of the skin that have been excised and resolved, in situ cervical cancer or prostatic cancer with normal prostatic specific antigen
* Clinical evidence of severe uncontrolled depression, active suicidal ideation or suicide attempt
* Any other significant medical or psychiatric conditions that, in the opinion of the Investigator, would preclude participation in the trial or impair the ability to give informed consent
* Major surgery in the 4 weeks prior to screening (Visit 1)
* Known hypersensitivity to the trial medication or diluents
* Participation in another clinical trial within the 30 days prior to screening (Visit 1)
* Pregnancy, lactation or a positive pregnancy test during screening (urine dipstick) or at Visit 4 (serum beta-human chorionic gonadotrophin \[beta-hCG\]), or intention to become pregnant or to breast-feed during the course of the trial
* Legal incapacity or limited legal capacity

Primary outcomes:
measure: Change From Baseline in the Average Number of Time Constant 1 (T1) Contrast-enhanced Lesions (CELs) Over On-treatment Scans
timeFrame: Baseline (Weeks -8, -4 and 0), Treatment Period (Weeks 12, 16 and 20)
Secondary outcomes:
measure: Total Number of Time Constant 1 (T1) Contrast-enhanced Lesions (CELs)
timeFrame: Weeks 12, 16, 20, 24, 28 and 36
measure: Change From Baseline in Total Number of Time Constant 1 (T1) Contrast-enhanced Lesions (CELs) at Weeks 12, 16, 20, 24, 28 and 36
timeFrame: Baseline (Weeks -8, -4 and 0), Weeks 12, 16, 20, 24, 28 and 36
measure: Change From Baseline in Total Volume of Time Constant 1 (T1) Contrast-enhanced Lesions (CELs) at Weeks 12, 16, 20, 24, 28 and 36
timeFrame: Baseline (Weeks -8, -4, 0), Week 12, 16, 20, 24, 28 and 36
measure: Total Number of New or Newly Enlarging Time Constant 2 (T2) Lesions
timeFrame: Weeks 12, 16, 20, 24, 28 and 36
measure: Change From Week 0 in Total Number of Time Constant 1 (T1) Contrast-enhanced Lesions (CELs) at Weeks 12, 16, 20, 24, 28 and 36
timeFrame: Week 0, 12, 16, 20, 24, 28 and 36
measure: Change From Week 0 in Total Volume of Time Constant 1 (T1) Contrast-enhanced Lesions (CELs) at Weeks 12, 16, 20, 24, 28 and 36
timeFrame: Weeks 0, 12, 16, 20, 24, 28 and 36
measure: Mean Annualized Relapse Rate
timeFrame: Week 20
measure: Time to First Relapse
timeFrame: Baseline up to Week 36
measure: Change From Baseline in Total Expanded Disability Status Scale (EDSS) Score at Week 20
timeFrame: Baseline (Week 0) and Week 20
measure: Change From Baseline in Total Multiple Sclerosis Functional Composite (MSFC) Score at Week 20
timeFrame: Baseline (Week 0) and Week 20
measure: Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation
timeFrame: Baseline up to Week 25
measure: Number of Subjects Experiencing Injection Site Reactions (ISRs)
timeFrame: Baseline up to Week 22
Other outcomes:
Locations:
city: Darmstadt
country: Germany
facility: Please contact the Merck KGaA Communication Center
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: