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ATX-MS-1467 in Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT01973491
Recruitment Status : Completed
First Posted : October 31, 2013
Results First Posted : April 13, 2017
Last Update Posted : July 2, 2017
Sponsor:
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Tracking Information
First Submitted Date  ICMJE October 23, 2013
First Posted Date  ICMJE October 31, 2013
Results First Submitted Date  ICMJE March 1, 2017
Results First Posted Date  ICMJE April 13, 2017
Last Update Posted Date July 2, 2017
Actual Study Start Date  ICMJE February 28, 2014
Actual Primary Completion Date April 30, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 1, 2017)
Change From Baseline in the Average Number of Time Constant 1 (T1) Contrast-enhanced Lesions (CELs) Over On-treatment Scans [ Time Frame: Baseline (Weeks -8, -4 and 0), Treatment Period (Weeks 12, 16 and 20) ]
T1 CELs were measured using Magnetic Resonance Imaging (MRI) scans. Baseline value was calculated as the average number of T1 CELs during the 3 visits in the Baseline Control Period (Weeks -8, -4 and 0) and On-treatment value was calculated as the average number of T1 CELs during the 3 visits in the treatment period (Weeks 12, 16 and 20). The change from baseline in average number of T1 CELs was reported.
Original Primary Outcome Measures  ICMJE
 (submitted: October 25, 2013)
Change in the average number of time constant 1 (T1) contrast-enhanced lesions (CEL) at three on-treatment scans (Weeks 12, 16 and 20) compared to the average number of T1 CEL at three Baseline scans (Weeks -8, -4 and 0) [ Time Frame: Weeks -8, -4, 0, 12, 16 and 20 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 1, 2017)
  • Total Number of Time Constant 1 (T1) Contrast-enhanced Lesions (CELs) [ Time Frame: Weeks 12, 16, 20, 24, 28 and 36 ]
    The number of T1 CELs were measured using MRI scans.
  • Change From Baseline in Total Number of Time Constant 1 (T1) Contrast-enhanced Lesions (CELs) at Weeks 12, 16, 20, 24, 28 and 36 [ Time Frame: Baseline (Weeks -8, -4 and 0), Weeks 12, 16, 20, 24, 28 and 36 ]
    T1 CELs were measured using MRI scans. Baseline was calculated as the average number of T1 CELs during the 3 visits in the Baseline Control Period (Weeks -8, -4 and 0).
  • Change From Baseline in Total Volume of Time Constant 1 (T1) Contrast-enhanced Lesions (CELs) at Weeks 12, 16, 20, 24, 28 and 36 [ Time Frame: Baseline (Weeks -8, -4, 0), Week 12, 16, 20, 24, 28 and 36 ]
    T1 CELs were measured using MRI scans. Baseline was calculated as the average number of T1 CELs during the 3 visits in the Baseline Control Period (Weeks -8, -4 and 0).
  • Total Number of New or Newly Enlarging Time Constant 2 (T2) Lesions [ Time Frame: Weeks 12, 16, 20, 24, 28 and 36 ]
    T2 lesions were measured using MRI scans.
  • 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 [ Time Frame: Week 0, 12, 16, 20, 24, 28 and 36 ]
    T1 CELs were measured using MRI scans.
  • 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 [ Time Frame: Weeks 0, 12, 16, 20, 24, 28 and 36 ]
    T1 CELs were measured using MRI scans.
  • Mean Annualized Relapse Rate [ Time Frame: Week 20 ]
    Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. These new or worsening symptoms should be noted by the subject and must be accompanied by at least one of the following: An increase of greater than or equal to (>=) 1 grade in >=2 functional scales of the Expanded Disability Status Scale (EDSS) or an increase of >=2 grades in 1 functional scale of the EDSS or an increase of >= 0.5 or an increase of >=1.0 in EDSS if the previous EDSS was 0. Annualized Relapse Rate was calculated as = 365.25 x (Number of relapses during Treatment Period) per (Number of days on treatment during Treatment Period).
  • Time to First Relapse [ Time Frame: Baseline up to Week 36 ]
    Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. These new or worsening symptoms should be noted by the subject and must be accompanied by at least one of the following: An increase of greater than or equal to (>=) 1 grade in >=2 functional scales of the Expanded Disability Status Scale (EDSS) or an increase of >=2 grades in 1 functional scale of the EDSS or an increase of >= 0.5 or an increase of >=1.0 in EDSS if the previous EDSS was 0. Time to first relapse was defined as the time in days from the date of first dose of study treatment to the date of first multiple sclerosis relapse.
  • Change From Baseline in Total Expanded Disability Status Scale (EDSS) Score at Week 20 [ Time Frame: Baseline (Week 0) and Week 20 ]
    EDSS is an ordinal scale in half-point increments that qualifies disability in subjects with Multiple Sclerosis. It consists of 8 ordinal rating scales assessing seven functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as any other neurological findings due to Multiple Sclerosis. Total EDSS score ranges from 0 (normal neurological examination) to 10 (death due to MS). Baseline was defined as the last measurement taken prior to the first dose of study drug (Week 0).
  • Change From Baseline in Total Multiple Sclerosis Functional Composite (MSFC) Score at Week 20 [ Time Frame: Baseline (Week 0) and Week 20 ]
    The MSFC is a multidimensional clinical outcome measure which consists of three sub-tests; Timed 25-Foot Walk, 9-Hole Peg Test and Paced Auditory Serial Addition Test-3(PASAT-3). The Timed 25-Foot Walk is a quantitative measure of lower extremity function. The 9-Hole Peg Test is a quantitative measure of upper extremity (arm and hand) function. The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Standardized results (Z-scores) of these sub-tests and the overall MSFC Z-score as an average of these three Z-scores was calculated. Higher Z-scores reflect better neurological function and a positive change from baseline indicates improvement. An increase in score indicates an improvement (range -3 to +3). Baseline was defined as the last measurement taken prior to the first dose of study drug (Week 0).
  • Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation [ Time Frame: Baseline up to Week 25 ]
    An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the study drug. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent adverse events are defined as any adverse event with a start date on or after the date of first dose and within 28 days after the date of last dose in the current study. TEAEs include both Serious TEAEs and non-serious TEAEs.
  • Number of Subjects Experiencing Injection Site Reactions (ISRs) [ Time Frame: Baseline up to Week 22 ]
    Treatment-emergent ISRs were defined as any ISR with a start date on or after the date of first dose and within 7 days after the date of last dose in the current study. Injection site reactions were identified as erythema, induration, pruritus, nodules and/or cysts, ecchymosis, pain and local edema.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2013)
  • Number of T1 CEL [ Time Frame: Weeks 12, 16, 20, 24, 28 and 36 ]
  • Change from Baseline (average of 3 Baseline scans, Weeks -8, -4 and 0) in total number of T1 CEL at Weeks 12, 16, 20, 24, 28 and 36 [ Time Frame: Weeks -8, -4, 0, 12, 16, 20, 24, 28 and 36 ]
  • Change from Baseline (average of 3 Baseline scans, Weeks -8, -4 and 0) in total volume of T1 CEL at Weeks 12, 16, 20, 24, 28 and 36 [ Time Frame: Weeks -8, -4, 0, 12, 16, 20, 24, 28 and 36 ]
  • Number of new or newly enlarging time constant 2 (T2) lesions [ Time Frame: Weeks 12, 16, 20, 24, 28 and 36 ]
  • Change from Baseline (Week 0) in total number of T1 CEL at Weeks 12, 16, 20, 24, 28 and 36 [ Time Frame: Week 0, 12, 16, 20, 24, 28 and 36 ]
  • Change from Baseline (Week 0) in total volume of T1 CEL at Weeks 12, 16, 20, 24, 28 and 36 [ Time Frame: Weeks 0, 12, 16, 20, 24, 28 and 36 ]
  • Mean Annualized Relapse Rate [ Time Frame: Week 20 ]
  • Time to First Relapse [ Time Frame: Baseline up to Week 36 ]
  • Change from Baseline (Week 0) in total expanded disability status scale (EDSS) score at Week 20 [ Time Frame: Week 0 and Week 20 ]
  • Change from Baseline (Week 0) in total multiple sclerosis functional composite (MSFC) score at Week 20 [ Time Frame: Week 0 and Week 20 ]
  • Change from Baseline (Week 0) in myelin basic protein (MBP)-induced peripheral blood mononuclear cells (PBMC) proliferation at Week 20 [ Time Frame: Week 0 and Week 20 ]
  • Change from Week 20 in MBP-PBMC proliferation at Week 36 [ Time Frame: Week 20 and Week 36 ]
  • Number of subjects with treatment-emergent adverse events (TEAEs) [ Time Frame: Baseline up to Week 36 ]
  • Number of Subjects Experiencing Injection Site Reactions (ISRs) [ Time Frame: Baseline up to Week 24 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ATX-MS-1467 in Multiple Sclerosis
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis
Intervention  ICMJE Drug: ATX-MS-1467
Subjects will receive ATX-MS-1467 50 microgram (mcg), 200 mcg and 800 mcg on Day 1, Day 15 and Day 29 respectively during the titration period followed by biweekly dose of ATX-MS-1467 800 mcg for 16 weeks during the treatment period.
Other Names:
  • M2736
  • IL-10 Inducer
Study Arms  ICMJE Experimental: ATX-MS-1467
Intervention: Drug: ATX-MS-1467
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 1, 2017)
37
Original Estimated Enrollment  ICMJE
 (submitted: October 25, 2013)
20
Actual Study Completion Date  ICMJE April 30, 2016
Actual Primary Completion Date April 30, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01973491
Other Study ID Numbers  ICMJE 200166-001
2013-002916-28 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Merck KGaA, Darmstadt, Germany
Study Sponsor  ICMJE Merck KGaA, Darmstadt, Germany
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Responsible Merck KGaA, Darmstadt, Germany
PRS Account Merck KGaA, Darmstadt, Germany
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP