Author Topic: (Abst.) Safety and efficacy of oral ozanimod in RRMS: phase 2, RADIANCE study  (Read 73 times)

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Offline agate

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From Lancet Neurology, February 18, 2016:

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Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo-controlled, phase 2 trial

Dr Jeffrey A Cohen, MD, Douglas L Arnold, MD, Giancarlo Comi, MD, Amit Bar-Or, MD, Sheila Gujrathi, MD, Jeffrey P Hartung, PhD, Matt Cravets, MA, Allan Olson, MD, Paul A Frohna, MD, Krzysztof W Selmaj, MD for the RADIANCE Study Group


Modulation of sphingosine 1-phosphate (S1P) receptors in a non-selective manner decreases disease activity in patients with multiple sclerosis but has potential safety concerns. We assessed the safety and efficacy of the oral selective S1P receptor modulator ozanimod in patients with relapsing multiple sclerosis.

Methods

RADIANCE is a combined phase 2/3 trial. Patients with relapsing multiple sclerosis were recruited from 55 academic and private multiple sclerosis clinics in 13 countries across Europe and the USA. Eligible participants were aged 1855 years, had an Expanded Disability Status Scale (EDSS) score of 050, and had either one or more relapses in the previous 12 months, or one or more relapses in the past 24 months and one or more gadolinium-enhancing lesions on MRI in the previous 12 months before screening.

Participants were assigned by a computer-generated randomisation sequence in a 1:1:1 ratio to ozanimod (05 mg or 1 mg) or matching placebo once daily for 24 weeks by an independent, unmasked, statistical team. Trial participants, study site personnel, MRI assessors, steering committee members, and the study statistician were masked to treatment assignment.

To attenuate first-dose cardiac effects, ozanimod was up-titrated from 025 mg to 05 mg or 1 mg over 8 days. The primary endpoint was the cumulative number of total gadolinium-enhancing MRI lesions measured by an independent MRI analysis centre at weeks 1224 after treatment initiation. Analysis was by intention to treat.

Here, we report results from the 24-week phase 2 trial. This trial is registered with ClinicalTrials.gov, number NCT01628393. The 2-year phase 3 trial is ongoing.

Findings

The first patient was randomised on Oct 18, 2012, and the final visit of the last randomised patient was on May 11, 2014. The intention-to-treat and safety population consisted of 258 participants, 88 were assigned placebo, 87 ozanimod 05 mg, and 83 ozanimod 1 mg; 252 (98%) patients completed the assigned treatment.

The mean cumulative number of gadolinium-enhancing lesions at weeks 1224 was 111 (SD 299) with placebo compared with 15 (37) with ozanimod 05 mg (odds ratio 016, 95% CI 008030; p<00001) and 15 (34) with ozanimod 1 mg (odds ratio 011, 95% CI 006021; p<00001).

Three serious adverse events unrelated to treatment were reported in patients assigned ozanimod 05 mg: optic neuritis, somatoform autonomic dysfunction, and cervical squamous metaplasia (HPV-related). No serious infectious or cardiac adverse events were reported, and no cases of macular oedema arose.

The most common adverse events in the ozanimod 05 mg and 1 mg groups compared with placebo were nasopharyngitis (11 and five vs 12), headache (five and three vs eight), and urinary-tract infections (six and two vs two).

The maximum reduction in mean heart rate by Holter monitoring during the first 6 h in ozanimod-treated participants was less than 2 beats per min (bpm) compared with baseline, with no patient having a minimum hourly heart rate less than 45 bpm. Electrocardiograms and 24-h Holter monitoring showed no increased incidence of atrioventricular block or sinus pause with ozanimod.

Interpretation

Ozanimod significantly reduced MRI lesion activity in participants with relapsing multiple sclerosis, with a favourable safety profile over a period of 24 weeks. These findings warrant phase 3 trials, which are ongoing.

_______________________

Funding
Receptos, Inc.

The abstract can be seen here.
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SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.

Offline agate

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An article about ozanimod from the MSAA Research News, April 28, 2016:

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Trial Results Presented for Oral Ozanimod


[In] February, the 72-week Phase II results were presented from the RADIANCE trial, which studied the effectiveness of ozanimod treatment in individuals with relapsing-remitting MS (RRMS). Previously known as RPC1063, this investigational medication is now under development by Celgene Corporation.

Ozanimod is a selective S1P 1 and 5 receptor modulator. It was given as a once-daily pill in the Phase II RADIANCE trial and was compared at two different doses (0.5 mg and 1 mg) with placebo. A total of 258 RRMS patients were studied in this double-blind trial, which ran for 24 weeks and was then followed by a 48-week blinded-extension period. After the initial 24 weeks, individuals taking the placebo were randomized to either dose of the medication.

At the conclusion of the 72-week study, patients in groups taking either dose of ozanimod showed a significant decrease in the mean number of gadolinium-enhanced (GdE) lesions. A significant number of participants were also free of GdE lesions, and relapse rates were reduced as well.

The most common side effects reported were minor infections, back pain, and headache. Elevated liver enzymes were seen in 3 to 4 percent of the participants. No serious cardiac events were reported.

Ozanimod is now being studied in two Phase III trials, SUNBEAM and a two-year portion of RADIANCE.

MS Speaks--online for 13 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.