Safety and efficacy of opicinumab in patients with relapsing multiple sclerosis (SYNERGY): a randomised, placebo-controlled, phase 2 trial.

Safety and efficacy of opicinumab in patients with relapsing multiple sclerosis (SYNERGY): a randomised, placebo-controlled, phase 2 trial.

Publication date: Jul 05, 2019

Opicinumab is a human monoclonal antibody against LINGO-1, an inhibitor of oligodendrocyte differentiation and axonal regeneration. Previous findings suggested that opicinumab treatment might enhance remyelination in patients with CNS demyelinating diseases. We aimed to assess the safety and efficacy of opicinumab in patients with relapsing multiple sclerosis.

We did a randomised, double-blind, placebo-controlled, dose-ranging, phase 2 study (SYNERGY) at 72 sites in 12 countries. Participants (aged 18-58 years) with relapsing multiple sclerosis (relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis with relapses) were randomised in a 1:2:2:2:2 ratio by an interactive voice and web response system to opicinumab 3 mg/kg, 10 mg/kg, 30 mg/kg, or 100 mg/kg, or placebo. An identical volume of study drug was administered intravenously once every 4 weeks. All participants self-administered intramuscular interferon beta-1a as background anti-inflammatory treatment once a week. The primary endpoint was the percentage of participants achieving confirmed disability improvement over 72 weeks, which was a multicomponent endpoint measured by the Expanded Disability Status Scale, the Timed 25-Foot Walk, the Nine-Hole Peg Test, and the 3 s Paced Auditory Serial Addition Test. The primary endpoint was analysed under intention-to-treat principles. This study is registered at ClinicalTrials.gov, number NCT01864148.

Between Aug 13, 2013, and July 31, 2014, 419 patients were enrolled and randomly assigned either placebo (n=93) or opicinumab 3 mg/kg (n=45), 10 mg/kg (n=95), 30 mg/kg (n=94; one patient did not receive the assigned treatment), or 100 mg/kg (n=92). The last patient visit was on March 29, 2016. Confirmed disability improvement over 72 weeks was seen in 45 (49%) of 91 patients assigned to placebo, 21 (47%) of 45 assigned to opicinumab 3 mg/kg, 59 (63%) of 94 assigned to opicinumab 10 mg/kg, 59 (65%) of 91 assigned to opicinumab 30 mg/kg, and 36 (40%) of 91 assigned to opicinumab 100 mg/kg. A linear dose-response in the probability of confirmed disability improvement was not seen (linear trend test p=0.89). Adverse events occurred in 79 (85%) patients assigned placebo and in 275 (85%) assigned any dose of opicinumab. The most common adverse events of any grade in patients assigned any dose of opicinumab included influenza-like illness (140 [43%] with any dose of opicinumab vs 37 [40%] with placebo), multiple sclerosis relapses (117 [36%] vs 30 [32%]), and headache (51 [16%] vs 23 [25%]). Serious adverse events reported as related to treatment were urinary tract infection in one (1%) participant in the the placebo group, suicidal ideation and intentional overdose in one (1%) participant in the 30 mg/kg opicinumab group, bipolar disorder in one (1%) participant in the 100 mg/kg opicinumab group, and hypersensitivity in four (4%) participants in the 100 mg/kg opicinumab group. One patient in the opicinumab 30 mg/kg group died during the study due to a traffic accident, which was not considered related to study treatment.

Our findings did not show a significant dose-linear improvement in disability compared with placebo in patients with relapsing multiple sclerosis. Further studies are needed to investigate whether some subpopulations identified in the study might benefit from opicinumab treatment at an optimum dose.

Biogen.

Cadavid, D., Mellion, M., Hupperts, R., Edwards, K.R., Calabresi, P.A., Drulovi’c, J., Giovannoni, G., Hartung, H.P., Arnold, D.L., Fisher, E., Rudick, R., Mi, S., Chai, Y., Li, J., Zhang, Y., Cheng, W., Xu, L., Zhu, B., Green, S.M., , Chang, Deykin, A., Sheikh, S.I., and investigators, SYNERGY study. Safety and efficacy of opicinumab in patients with relapsing multiple sclerosis (SYNERGY): a randomised, placebo-controlled, phase 2 trial. 18543. 2019 Lancet Neurol.

Concepts Keywords
Axonal Regeneration Illness
Biogen Influenza
Bipolar Disorder Diseases
Demyelinating Diseases Placebo multiple sclerosis
Disability Headache
Dose Response Clinical research
Double Blind Health
Headache Medicine
Hole Deception
Hypersensitivity Placebo
Influenza Articles
Inhibitor
Interferon Beta 1a
Intramuscular
Intravenously
Lancet
Monoclonal Antibody
Multiple Sclerosis
Oligodendrocyte
Overdose
Placebo
Primary Endpoint
Probability
Progressive
Suicidal Ideation
Test
Urinary Tract Infection

Semantics

Type Source Name
disease DOID hypersensitivity
disease MESH hypersensitivity
disease DOID bipolar disorder
disease MESH bipolar disorder
disease MESH suicidal ideation
disease DOID urinary tract infection
disease MESH urinary tract infection
disease DOID influenza
disease MESH influenza
gene UNIPROT CEP55
drug DRUGBANK Polyethylene glycol
gene UNIPROT TMEM121
drug DRUGBANK Interferon beta-1a
disease MESH relapses
disease DOID secondary progressive multiple sclerosis
disease MESH secondary progressive multiple sclerosis
disease DOID relapsing-remitting multiple sclerosis
disease MESH relapsing-remitting multiple sclerosis
disease MESH demyelinating diseases
disease DOID multiple sclerosis
disease MESH multiple sclerosis

Similar

Original Article

Leave a Comment

Your email address will not be published. Required fields are marked *