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A Study to Assess the Effect of a Single Infusion of VAY736 on Disease Activity in Patients With Relapsing-remitting Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT02038049
Recruitment Status : Terminated (The study recruitment was terminated based on strategic considerations after 8 patients were enrolled.)
First Posted : January 16, 2014
Results First Posted : October 30, 2019
Last Update Posted : October 30, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE January 14, 2014
First Posted Date  ICMJE January 16, 2014
Results First Submitted Date  ICMJE August 13, 2019
Results First Posted Date  ICMJE October 30, 2019
Last Update Posted Date October 30, 2019
Actual Study Start Date  ICMJE December 20, 2013
Actual Primary Completion Date May 5, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 25, 2019)
Number of New T1-weighted Gadolinium (Gd)-Enhancing Lesions at Weeks 8, 12 and 16 [ Time Frame: Week 8, Week 12, Week 16 ]
The effect of VAY736, compared to placebo on the cumulative number of new gadolinium [Gd]-enhancing lesions on T1-weighted brain MRI scans in relapsing-remitting multiple sclerosis (RRMS) patient population at weeks 8, 12 and 16. Only descriptive statistics performed.
Original Primary Outcome Measures  ICMJE
 (submitted: January 14, 2014)
Cumulative number of new Gd-enhancing lesions [ Time Frame: 8, 12, 16 weeks ]
The primary objective is to evaluate the effect of VAY736 on the cumulative number of new Gd-enhancing brain lesions in RRMS patient population at weeks 8, 12 and 16. It will be analyzed by means of a negative binomial regression model (with factor "treatment") adjusting for baseline lesion count and number of MRI scans.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2019)
  • Number of All T1-weighted Gadolinium (Gd)-Enhancing Lesions at Weeks 4, 8, 12 and 16 [ Time Frame: Week 4, Week 8, Week 12, Week 16 ]
    Magnetic resonance imaging (MRI) scanning of the brain was performed at screening/baseline, week 4, week 8, week 12 and week 16 to assess all T1-weighted Gadolinium (Gd) enhancing lesions. Each MRI scan was reviewed by a local neuro-radiologist. Only descriptive statistics performed.
  • Number of New T1-weighted Gadolinium (Gd)-Enhancing Lesions at Weeks 4, 8, 12 and 16 [ Time Frame: Week 4, Week 8, Week 12, Week 16 ]
    Magnetic resonance imaging (MRI) scanning of the brain was performed at screening/baseline, week 4, week 8, week 12 and week 16 to assess all new T1-weighted Gadolinium (Gd) enhancing lesions. Each MRI scan was reviewed by a local neuro-radiologist. Only descriptive statistics performed.
  • Number of New or Enlarging T2-weighted Gadolinium (Gd)-Enhancing Lesions at Weeks 4, 8, 12 and 16 [ Time Frame: Week 4, Week 8, Week 12, Week 16 ]
    Magnetic resonance imaging (MRI) scanning of the brain was performed at screening/baseline, week 4, week 8, week 12 and week 16 to assess T2 hyperintense lesions (new or enlarging T2-weighted lesions). Each MRI scan was reviewed by a local neuro-radiologist. Only descriptive statistics performed.
  • T2 Burden of Disease (Total Volume of T2-weighted Lesions) at Weeks 4, 8, 12 and 16. [ Time Frame: Week 4, Week 8, Week 12, Week 16 ]
    Magnetic resonance imaging (MRI) scanning of the brain was performed at screening/baseline, week 4, week 8, week 12 and week 16 to assess T2 burden of disease. Each MRI scan was reviewed by a local neuro-radiologist. Only descriptive statistics performed.
  • Number of Subjects Without Any New MRI Disease Activity at Weeks 4, 8, 12 and 16. [ Time Frame: Week 4, Week 8, Week 12, Week 16 ]
    Magnetic resonance imaging (MRI) scanning of the brain was performed at screening/baseline, week 4, week 8, week 12 and week 16 to assess patients without any new MRI disease activity (no new Gd-enhancing lesions nor new or enlarging T2 lesions). Each MRI scan was reviewed by a local neuro-radiologist. Only descriptive statistics performed.
  • Proportion of Relapse-free Patients Over the 16 Weeks of the Treatment Period. [ Time Frame: Week 0 (Day 1), Week 4, Week 8, Week 12, Week 16 ]
    A relapse is defined as the appearance of a new neurological abnormality, or worsening of previously stable, or improving pre-existing neurological abnormality, separated by at least 30 days from the onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5 C) or infection. A relapse was considered confirmed when confirmed by an Extended disability status scale (EDSS)-certified physician who was not involved in the treatment of the patient, was blinded to treatment allocation, and had no access to patient medical records. It was recommended that this occurs within 5 days of the onset of symptoms. A relapse was confirmed when it was accompanied by an increase of at least half a point (0.5) on the EDSS or an increase of 1 point on two different Functional Systems (FS) of the EDSS or 2 points on one of the FS (excluding Bowel/Bladder or Cerebral FS). Only descriptive statistics performed.
  • Number of Participants With On-Treatment Adverse Events, Serious Adverse Event, and Death [ Time Frame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS) depending on B cell recovery (ranging from week 48 to 216) ]
    Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) to demonstrate that VAY736 is safe for the treatment of patients with relapsing-remitting multiple sclerosis through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive statistics performed.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 14, 2014)
  • Number of new and cumulative number of new T1-weighted Gd-enhancing lesions at weeks 4, 8, 12 and 16 [ Time Frame: 4, 8, 12, 16 weeks ]
    It will be compared separately at each week between treatment groups using a negative binomial regression model adjusting for baseline lesion count and number of MRI scans.
  • Number of all T1-weighted Gd-enhancing lesions at weeks 4, 8, 12 and 16 [ Time Frame: 4, 8, 12, 16 weeks ]
    It will be compared separately at each week between treatment groups using a negative binomial regression model adjusting for baseline lesion count and number of MRI scans
  • Cumulative number of new or enlarging T2-weighted Gd-enhancing lesions at weeks 4, 8, 12 and 16 [ Time Frame: 4, 8, 12, 16 weeks ]
    It will be compared between treatment groups using a negative binomial regression model adjusting for baseline lesion count and number of MRI scans.
  • T2 Burden of Disease (Total Volume of T2-weighted Lesions) at Weeks 4, 8, 12 and 16. [ Time Frame: 4, 8, 12, 16 weeks ]
    Change from baseline will be analyzed by ANCOVA separately at each week
  • Proportion of subjects without any new MRI disease activity at weeks 4, 8, 12 and 16. [ Time Frame: 4, 8, 12, 16 weeks ]
    At each week, the proportion between treatment groups will be compared using a logistic regression model adjusting for baseline lesion count.
  • The number of confirmed relapses at week 16. [ Time Frame: 16 Weeks ]
    It will be compared using a negative binomial regression adjusting for baseline number of relapses in previous 2 years and log (time on study in years) as the offset variable.
  • Proportion of relapse-free patients over the 16 weeks of the treatment period. [ Time Frame: 16 weeks ]
    It will be compared between treatment groups using a logistic regression model adjusting for baseline number of relapses in previous 2 years.
  • Number of patients with adverse events [ Time Frame: Estimated mean 24 weeks ]
    Summarized statistics on adverse events will be reported under categories such as total adverse events, serious adverse events and death
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess the Effect of a Single Infusion of VAY736 on Disease Activity in Patients With Relapsing-remitting Multiple Sclerosis
Official Title  ICMJE A Randomized, Partially Blind, Placebo-controlled, Proof-of-concept Study to Assess the Effect of a Single Infusion of VAY736 on Disease Activity as Measured by Brain MRI Scans in Patients With Relapsing-remitting Multiple Sclerosis
Brief Summary This was a randomized, partially blinded, placebo-controlled, non-confirmatory study to assess the effects of a single infusion of VAY736 on disease activity as measured by brain MRI scans in patients with relapsing-remitting multiple sclerosis (RRMS).
Detailed Description The study was planned to be conducted in approximately 96 patients. However, after enrolling 8 patients, the recruitment was terminated based on strategic considerations.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Relapse Remitting Multiple Sclerosis
Intervention  ICMJE
  • Drug: VAY736
    Single intravenous infusion of VAY736 (10 mg/kg)
    Other Name: Lanalumab
  • Drug: Placebo
    Placebo to VAY736
Study Arms  ICMJE
  • Experimental: VAY736
    Intravenous infusion of VAY736
    Intervention: Drug: VAY736
  • Placebo Comparator: Placebo to VAY736
    Matching placebo (infusion bag) administered intravenously. Placebo randomized patients were offered optional VAY736 administration after week 16
    Intervention: Drug: Placebo
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 Terminated
Actual Enrollment  ICMJE
 (submitted: February 22, 2017)
8
Original Estimated Enrollment  ICMJE
 (submitted: January 14, 2014)
96
Actual Study Completion Date  ICMJE September 13, 2018
Actual Primary Completion Date May 5, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key inclusion criteria:

  • Male and female patients aged 18 to 55 years.
  • Diagnosis of MS as defined by the 2010 revised McDonald criteria (Polman et al 2011).
  • A relapsing-remitting course of disease with:

    • at least 1 documented relapse during the previous 12 months (but not within 30 days prior to randomization ), or
    • a positive Gd-enhancing lesion on brain MRI scan at screening.
  • An Expanded Disability Status Scale (EDSS) score of 0-5.0 inclusive at screening.
  • No evidence of a relapse within 30 days prior to randomization.

Key exclusion criteria:

  • A manifestation of another type of MS other than RRMS.
  • Findings on screening or baseline brain MRI inconsistent with the diagnosis of MS.
  • History of chronic disease of the immune system other than MS, or a known immunodeficiency syndrome.
  • Score "yes" on item 4 or item 5 of the Suicidal Ideation section of the C-SSRS, if this ideation occurred in the past 6 months, or "yes" on any item of the Suicidal Behavior section, except for the "Non-Suicidal Self-Injurious Behavior" (item also included in the Suicidal Behavior section), if this behavior occurred in the past 2 years.
  • Women of child-bearing potential and Pregnant or nursing (lactating) women.
  • Screening CBC (complete blood count) laboratory values as follows:
  • Hemoglobin levels below 10.0 g/dL
  • Total leukocyte count less than 3,000 cells/µL
  • Neutropenia, defined as absolute neutrophil counts less than 1500 cells/mm3
  • Platelets less than 100,000/µL
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Czechia,   Ukraine,   United States
Removed Location Countries Czech Republic,   Germany,   Poland,   Russian Federation
 
Administrative Information
NCT Number  ICMJE NCT02038049
Other Study ID Numbers  ICMJE CVAY736X2202
2013-002324-16 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date October 2019

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