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#Post#: 1112--------------------------------------------------
(Abst.) Safety and efficacy of oral ozanimod in RRMS: phase 2, R
ADIANCE study
By: agate Date: February 18, 2016, 7:26 pm
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From Lancet Neurology, February 18, 2016:
[quote]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 18–55 years, had an
Expanded Disability Status Scale (EDSS) score of 0–5·0, 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 (0·5 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 0·25 mg to 0·5 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 12–24 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 0·5 mg, and
83 ozanimod 1 mg; 252 (98%) patients completed the assigned
treatment.
The mean cumulative number of gadolinium-enhancing lesions at
weeks 12–24 was 11·1 (SD 29·9) with placebo compared with 1·5
(3·7) with ozanimod 0·5 mg (odds ratio 0·16, 95% CI 0·08–0·30;
p<0·0001) and 1·5 (3·4) with ozanimod 1 mg (odds ratio 0·11, 95%
CI 0·06–0·21; p<0·0001).
Three serious adverse events unrelated to treatment were
reported in patients assigned ozanimod 0·5 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 0·5 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.[/quote]
The abstract can be seen here
(HTM) http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(16)00018-1/fulltext?utm_source=USnewsletter51&utm_medium=email&utm_campaign=USnewsletter.
#Post#: 1195--------------------------------------------------
Trial results presented for oral ozanimod (RPC1063)(MSAA researc
h news)
By: agate Date: April 28, 2016, 12:45 pm
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An article about ozanimod from the MSAA Research News, April 28,
2016:
[quote]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.
[/quote]
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