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Efficacy Results of the Phase 2 Portion of the RADIANCE Trial: A Randomized, Double-blind, Placebo-controlled Trial of Oral RPC1063 in Adults with Relapsing Multiple Sclerosis (P7.198)

2015· article· en· W2345311615 on OpenAlexaff
Gıancarlo Comı, Jeffrey A. Cohen, Douglas L. Arnold, Amit Bar‐Or, Sheila Gujrathi, Jeffrey Hartung, Allan Olson, Matthew Cravets, Paul Frohna, Krzysztof Selmaj

Bibliographic record

VenueNeurology · 2015
Typearticle
Languageen
FieldMedicine
TopicCytokine Signaling Pathways and Interactions
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
Fundersnot available
KeywordsPlaceboDouble blindMedicineRandomized controlled trialMultiple sclerosisRadianceClinical trialSurgeryInternal medicinePsychiatryAlternative medicinePathologyGeography

Abstract

fetched live from OpenAlex

Objective: Demonstrate efficacy of low (LD, 0.5 mg) and high (HD, 1.0 mg) dose RPC1063 vs placebo (PBO) in relapsing multiple sclerosis (RMS). Background: RPC1063 is an oral sphingosine 1-phosphate (S1P) 1,5 receptor modulator in clinical development for RMS. Methods: RADIANCE is an ongoing international Phase 2/3 trial. In the 24-week, Phase 2 portion, 258 patients were randomized (1:1:1) to PBO (n=88), LD (n=87) or HD (n=83). The primary endpoint was cumulative number of total gadolinium-enhancing (GdE) MRI lesions from Wks 12-24. Key secondary endpoints included number of GdE lesions at Wk 24, cumulative number of new/enlarging T2 lesions from Wks 12-24, and annualized relapse rate (ARR). Results: 98[percnt] of patients completed the trial. Cumulative total Wk 12-24 GdE lesions decreased 86[percnt] in both RPC1063 arms vs PBO (mean±SD: PBO 11.1±29.9, LD 1.5±3.7, HD 1.5±3.4, p<0.0001). Numbers of GdE lesions at Wk 24 significantly decreased 91 and 94[percnt] vs PBO (PBO 3.2±9.8, LD 0.3±0.9, HD 0.2±0.6, both p<0.0001) and cumulative Wks 12-24 new/enlarging T2 lesions decreased 84 and 91[percnt] (PBO 9.0±20.9, LD 1.4±3.2, HD 0.8±1.9, both p<0.0001). Proportion of GdE lesion-free patients increased from baseline to Wk 24 with RPC1063 and decreased with PBO (PBO 70.5[percnt]-59.1[percnt], LD 60.9[percnt]-86.2[percnt], HD 62.7[percnt]-88.0[percnt], both doses p<0.0001 vs PBO at Wk 24). Time to first relapse increased with increasing dose with a significant increase in HD vs PBO (p=0.0397), while ARR reduction showed a favorable trend (LD: 31[percnt], p=0.27; HD: 53[percnt], p=0.053). Proportion of subjects with No Evidence of Disease Activity was significantly higher in both RPC1063 groups (LD 56.3[percnt], HD 55.4[percnt], PBO 26.1[percnt], both p<0.001). RPC1063 treatment was well tolerated with a good safety profile. Conclusions: Both doses of RPC1063 demonstrated significant efficacy on MRI measures, with the high dose also reducing clinical disease activity, supporting the ongoing Phase 3 portion (NCT02047734).

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.004
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.010
Threshold uncertainty score0.458

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.004
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.077
GPT teacher head0.314
Teacher spread0.238 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations5
Published2015
Admission routes1
Has abstractyes

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