Safety and Tolerability Results of the Phase 2 Portion of the RADIANCE Trial: A Randomized, Double-blind, Placebo-controlled Trial of Oral RPC1063 in Relapsing Multiple Sclerosis (P7.199)
Bibliographic record
Abstract
Objective: Characterize the safety and tolerability of RPC1063 in patients with relapsing multiple sclerosis (RMS). Background: RPC1063 is an oral sphingosine 1-phosphate (S1P) 1,5 receptor modulator in Phase 3 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 once daily PBO (n=88), low dose (LD, 0.5 mg, n=87), or high dose (HD, 1.0 mg, n=83) RPC1063. Safety was assessed using vital signs, clinical labs, ECG, 24-hour Holter, PFT, OCT, and adverse events (AEs). A 7-day dose titration was used to mitigate potential first dose heart rate (HR) effects. Results:98[percnt] of patients completed the trial, with 97[percnt] entering the blinded extension. AE profiles were comparable between groups. The most common AEs in combined RPC1063 vs PBO were nasopharyngitis (9.4 vs 13.6[percnt]), headache (4.7 vs 9.1[percnt]), and UTI (4.7 vs 2.3[percnt]). The majority of AEs were considered mild or moderate in severity and unrelated to RPC1063. Three unrelated serious AEs occurred, all in the LD group. During the first 6 hours post first dose of RPC1063, maximum reductions in mean hourly HR were <2 bpm from baseline and no patient had a minimum hourly HR <45 bpm. No clinically-significant bradycardia or conduction abnormalities (AV block, QT prolongation) were observed, and HR and blood pressure were similar between groups across the 24 weeks. Transient, isolated alanine aminotransferase 蠅3x ULN occurred in 3 patients (LD 2[2.3[percnt]]), HD 1[1.2[percnt]]), which decreased with continued treatment. There were no notable differences among treatment groups in PFTs or OCT measures, and no notable malignancies or serious infections observed. Conclusions: The tolerability and safety results suggest a favorable risk-benefit profile of RPC1063 in the treatment of RMS and support the ongoing Phase 3 portion of the RADIANCE trial of RPC1063 vs. interferon β-1a (NCT02047734).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".