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

Relapse Remitting Multiple Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02038049
• Other study ID #: CVAY736X2202
• Secondary ID: 2013-002324-16
• Status: Terminated
• Phase: Phase 2
• Start date: December 20, 2013
• Est. completion date: September 13, 2018

Study information

• Verified date: October 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: September 13, 2018
• Est. primary completion date: May 5, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapse Remitting Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• VAY736
Single intravenous infusion of VAY736 (10 mg/kg)
• Placebo
Placebo to VAY736

Locations

Country	Name	City	State
Czechia	Novartis Investigative Site	Hradec Kralove
Ukraine	Novartis Investigative Site	Kharkiv
Ukraine	Novartis Investigative Site	Lviv
United States	Novartis Investigative Site	Long Beach	California
United States	Novartis Investigative Site	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Czechia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Week 8, Week 12, Week 16
Secondary	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.	Week 4, Week 8, Week 12, Week 16
Secondary	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.	Week 4, Week 8, Week 12, Week 16
Secondary	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.	Week 4, Week 8, Week 12, Week 16
Secondary	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.	Week 4, Week 8, Week 12, Week 16
Secondary	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.	Week 4, Week 8, Week 12, Week 16
Secondary	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.	Week 0 (Day 1), Week 4, Week 8, Week 12, Week 16
Secondary	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.	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)

External Links

•   A Plain Language Trial Summary is available on novartisclinicaltrials.com