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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Primary Purpose

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

VAY736

Placebo

About this trial

This is an interventional treatment trial for Relapse Remitting Multiple Sclerosis focused on measuring Multiple Sclerosis, Relapsing-Remitting Multiple Sclerosis, Magnetic Resonance Imaging, VAY736, Lanalumab, monoclonal antibody, gadolinium [Gd]-enhancing lesions, B-Cell

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

VAY736

Placebo to VAY736

Arm Description

Intravenous infusion of VAY736

Matching placebo (infusion bag) administered intravenously. Placebo randomized patients were offered optional VAY736 administration after week 16

Outcomes

Primary Outcome Measures

Number of New T1-weighted Gadolinium (Gd)-Enhancing Lesions at Weeks 8, 12 and 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.

Secondary Outcome Measures

Number of All T1-weighted Gadolinium (Gd)-Enhancing Lesions at Weeks 4, 8, 12 and 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

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

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.

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.

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.

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

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.

Full Information

NCT ID

NCT02038049

First Posted

January 14, 2014

Last Updated

December 9, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02038049

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Terminated

Why Stopped

The study recruitment was terminated based on strategic considerations after 8 patients were enrolled.

Study Start Date

December 20, 2013 (Actual)

Primary Completion Date

May 5, 2015 (Actual)

Study Completion Date

September 13, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Relapse Remitting Multiple Sclerosis

Keywords

Multiple Sclerosis, Relapsing-Remitting Multiple Sclerosis, Magnetic Resonance Imaging, VAY736, Lanalumab, monoclonal antibody, gadolinium [Gd]-enhancing lesions, B-Cell

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

VAY736

Arm Type

Experimental

Arm Description

Intravenous infusion of VAY736

Arm Title

Placebo to VAY736

Arm Type

Placebo Comparator

Arm Description

Matching placebo (infusion bag) administered intravenously. Placebo randomized patients were offered optional VAY736 administration after week 16

Intervention Type

Drug

Intervention Name(s)

VAY736

Other Intervention Name(s)

Lanalumab

Intervention Description

Single intravenous infusion of VAY736 (10 mg/kg)

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo to VAY736

Primary Outcome Measure Information:

Title

Number of New T1-weighted Gadolinium (Gd)-Enhancing Lesions at Weeks 8, 12 and 16

Description

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.

Time Frame

Week 8, Week 12, Week 16

Secondary Outcome Measure Information:

Title

Number of All T1-weighted Gadolinium (Gd)-Enhancing Lesions at Weeks 4, 8, 12 and 16

Description

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.

Time Frame