NCT02241785: ESCALATE

Natalizumab as an Efficacy Switch in Participants With Relapsing Multiple Sclerosis After Failure on Other Therapies

Terminated Phase 4 Results posted Last updated 5 June 2017

What this trial tests

Phase 4 trial testing natalizumab in Relapsing Multiple Sclerosis in 47 participants. Terminated before completion.

Timeline

30 September 2014

Primary endpoint
2 May 2016

2 May 2016

Quick facts

Lead sponsor	Biogen
Phase	Phase 4
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	47
Start date	30 September 2014
Primary completion	2 May 2016
Estimated completion	2 May 2016
Sites	11 locations across United States

Drugs / interventions tested

• natalizumab (NATALIZUMAB) — full drug profile →

Conditions studied

• Relapsing Multiple Sclerosis — all drugs for Relapsing Multiple Sclerosis →

Sponsor

Biogen — full company profile →

Who can join

Adults 18 to 60, any sex, with Relapsing Multiple Sclerosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in T1 Unenhancing Lesion Volume and T2 Lesion Volume From Baseline (Day -1) to Reset Baseline (Week 8) Secondary · Baseline (Day -1) to Reset Baseline (Week 8)

As measured by magnetic resonance imaging.

Change in T1 Unenhancing Lesion Volume

Group	Value	95% CI
Natalizumab	0.11	± 0.65

Change in T2 Lesion Volume

Group	Value	95% CI
Natalizumab	0.01	± 1.76

Pre- and Post-Natalizumab Infusion Annualized Relapse Rate (ARR) Comparison at Month 12 Secondary · From 12 months prior to natalizumab infusion and 12 months post-natalizumab infusion

An MS relapse was defined as the onset of new or recurrent neurological symptoms lasting at least 24 hours, accompanied by new objective abnormalities on a neurological examination, and not explained solely by non-MS processes such as fever, infection, severe stress, or drug toxicity. 95% confidence interval is based on a Poisson regression model.

12 months pre-natalizumab infusion

Group	Value	95% CI
Natalizumab	1.553	1.306 – 1.847

12 months post-natalizumab infusion

Group	Value	95% CI
Natalizumab	0.159	0.076 – 0.331

Change in MSIS-29 Physical Impact Scores From Baseline (Day -1) to Reset Baseline (Week 8) Secondary · Baseline (Day -1) to Reset Baseline (Week 8)

The MSIS-29 is a brief self-administered MS-specific instrument measuring physical (20 items) and mental/psychological (9 items) impact of MS. The physical score is generated by summing individual items and then transforming to a scale with a range of 0 to 100, where high scores indicate worse health.

Group	Value	95% CI
Natalizumab	-2.53	± 12.42

Adverse events — posted to ClinicalTrials.gov

Time frame: From Screening through end of study. Duration of study treatment was up to 13 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Natalizumab

Serious: 2/47 (4%)

Deaths: —

Serious adverse events (2 terms)

Reaction	System	Natalizumab
Syncope	Nervous system disorders	—
Non-cardiac chest pain	General disorders	—

Most-reported serious reactions: Syncope, Non-cardiac chest pain.

Data from ClinicalTrials.gov NCT02241785 adverse events section.

Sponsor's own description

The primary objective of the study is to determine the efficacy of natalizumab (Tysabri, BG00002) in participants with relapsing forms of multiple sclerosis (MS) who have failed Gilenya or BRACET (Betaseron, Rebif, Avonex, Copaxone, Extavia, Tecfidera) as measured by the proportion of participants with no evidence of disease activity (NEDA) at Year 1. The secondary objectives in this study population are: change in total T1 hypointense and total T2 hyperintense lesion volume; proportion of participants with NEDA at Year 2; evaluation of the impact of natalizumab on annualized relapse rate (ARR); and change in Multiple Sclerosis Impact Scale-29 (MSIS-29) physical impact score.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Induction of Cardiac Pathology: Endogenous versus Exogenous Nrf2 Upregulation.
   Mathis BJ, Kato H, Hiramatsu Y. · · 2022 · cited 5× · PMID 36497112 · DOI 10.3390/cells11233855