Safety and efficacy of fulranumab in osteoarthritis of the hip and knee: results from four early terminated phase III randomized studies
Bibliographic record
Abstract
Objective: To evaluate the safety and efficacy of fulranumab as adjunct or monotherapy in patients with knee or hip pain related to moderate-to-severe osteoarthritis.Methods: Osteoarthritic patients (aged ≥18 years) from four phase 3 randomized, double-blind (DB), placebo-controlled studies were randomized to receive placebo, fulranumab 1 mg every 4 weeks (Q4wk), or 3 mg Q4wk in 16-week DB phase, followed by a 52-week post-treatment follow-up phase. Safety assessments included treatment-emergent adverse events (TEAEs), and neurological, sympathetic, and joint-related events of interest. Efficacy assessments included pain and physical function sub-scales of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores.Results: Of 245 patients from the ITT set (median age = 64 years; 62% women), 84 (34%) completed the DB phase; the majority of discontinuations (57%) were due to early study termination. In the DB phase, the incidence of TEAEs in fulranumab 3 mg (57.8%) and 1 mg (56.8%) was similar to placebo (56.8%). Two events adjudicated as joint-related events of interest include rapidly progressive osteoarthritis and fracture of unknown etiology. There were no new neurological TEAEs. Fulranumab showed evidence of efficacy in improving pain and physical function based on WOMAC sub-scale scores. Due to premature study termination, the number of patients enrolled were too small to make any definitive efficacy claims.Conclusions: Treatment with fulranumab was generally tolerated with no new safety signals. Within the limited sample analyzed, fulranumab showed evidence of improvement of pain and function in patients with moderate-to-severe osteoarthritis who had failed prior therapy and were candidates for joint replacement surgery.Clinical trial registration numbers: NCT02336685; NCT02336698; NCT02289716; NCT02301234KEY POINTSFulranumab as adjuvant or monotherapy was well tolerated with no new safety signalsFulranumab demonstrated evidence suggestive of efficacy in osteoarthritic pain of hip and kneeFulranumab demonstrated evidence suggestive of improvement of pain and physical function in osteoarthritis
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
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 teacher head, 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".