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Tanezumab for chronic low back pain: a randomized, double-blind, placebo- and active-controlled, phase 3 study of efficacy and safety.

ABSTRACT: This randomized, double-blind, Phase 3 study (56-week treatment; 24-week follow-up) assessed tanezumab in patients with chronic low back pain (CLBP) and history of inadequate response to standard-of-care analgesics (NCT02528253). Patients received placebo, subcutaneous tanezumab (5mg or 10mg every 8 weeks), or oral tramadol prolonged-release (100-300mg/day). Primary endpoint was change in Low Back Pain Intensity (LBPI) at week 16 for tanezumab versus placebo. Key secondary endpoints were proportion of patients with ?50% decrease in LBPI at week 16, change in Roland Morris Disability Questionnaire (RMDQ) at week 16, and change in LBPI at week 2 for tanezumab versus placebo. Adverse events and joint safety were assessed through weeks 56 and 80, respectively. Tanezumab 10mg met the primary endpoint by significantly improving LBPI at week 16 versus placebo; least squares (LS) mean (95% CI) difference = -0.40 (-0.76, -0.04; P=0.0281). Tanezumab 10mg significantly improved all key secondary endpoints. Tanezumab 5mg did not meet the primary endpoint (LS mean [95% CI] treatment difference versus placebo = -0.30 [-0.66, 0.07; P=0.1117]), preventing formal testing of key secondary endpoints for this dose. The proportion of patients with ?50% improvement in LBPI at week 16 was 37.4% in the placebo group, 43.3% in the tanezumab 5mg group (Odds ratio [95% CI] vs placebo = 1.28 [0.97, 1.70; P=0.0846]) and 46.3% in the tanezumab 10mg group (Odds ratio [95% CI] vs placebo = 1.45 [1.09, 1.91; P=0.0101]). Prespecified joint safety events were more frequent with tanezumab 10mg (2.6%) than tanezumab 5mg (1.0%), tramadol (0.2%), or placebo (0%). Seven patients, all in the tanezumab 10mg group (1.4%), underwent total joint replacement. In conclusion, tanezumab 10mg significantly improved pain and function versus placebo in patients with difficult-to-treat CLBP. Tanezumab was associated with a low rate of joint safety events, some requiring joint replacement. Sponsored by Pfizer Inc. and Eli Lilly & Company.

SUBMITTER: Markman JD

PROVIDER: S-EPMC7431140 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Tanezumab for chronic low back pain: a randomized, double-blind, placebo- and active-controlled, phase 3 study of efficacy and safety.

Markman John D JD Bolash Robert B RB McAlindon Timothy E TE Kivitz Alan J AJ Pombo-Suarez Manuel M Ohtori Seiji S Roemer Frank W FW Li David J DJ Viktrup Lars L Bramson Candace C West Christine R CR Verburg Kenneth M KM

Pain 20200901 9

<h4>Abstract</h4>This randomized, double-blind, phase 3 study (56-week treatment; 24-week follow-up) assessed tanezumab in patients with chronic low back pain and history of inadequate response to standard-of-care analgesics (NCT02528253). Patients received placebo, subcutaneous tanezumab (5 or 10 mg every 8 weeks), or oral tramadol prolonged-release (100-300 mg/day). Primary endpoint was change in low back pain intensity (LBPI) at week 16 for tanezumab vs placebo. Key secondary endpoints were p ...[more]

PMID: 32453139

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Project description:BackgroundAntagonism of chemoattractant receptor-homologous molecule on T-helper type-2 cells (CRTH2), a G-protein coupled receptor for prostaglandin D2, could be beneficial for treating allergic disorders. We present findings on the efficacy and safety/tolerability of a CRTH2 antagonist (setipiprant) in participants with seasonal allergic rhinitis (AR) in a real-life setting over 2 weeks.MethodsA Phase 2 trial and a Phase 3 trial were conducted at seven centers in Texas, USA during the Mountain Cedar pollen season. Both were prospective, randomized, double-blind, placebo- and active-referenced (cetirizine) studies. The Phase 2 trial assessed setipiprant 100-1000 mg b.i.d. and 1000 mg o.d. versus placebo in adult and elderly participants. The Phase 3 trial assessed setipiprant 1000 mg b.i.d. in adolescent, adult, and elderly participants. Efficacy was assessed using daytime nasal symptom scores (DNSS), night-time nasal symptom scores (NNSS) and daytime eye symptom scores (DESS).Results579 participants were randomized in the Phase 2 trial (mean age 41.6-43.4 years); 630 were randomized in the Phase 3 trial (mean age 37.5-40.7 years). A statistically significant, dose-related improvement in mean change from baseline DNSS was observed over 2 weeks with setipiprant 1000 mg b.i.d. versus placebo in the Phase 2 trial (-0.15 [95% CI -0.29, -0.01]; p = 0.030). Setipiprant 1000 mg b.i.d. had no significant effect on this endpoint in the Phase 3 trial (-0.02 [95% CI -0.12, 0.07]; p = 0.652). Total and individual NNSS and DESS symptom scores were significantly improved with setipiprant 1000 mg b.i.d. versus placebo in the Phase 2 but not the Phase 3 trial. Setipiprant showed a favorable safety/tolerability profile.ConclusionsThe Phase 2 trial was the first large clinical study to assess a CRTH2 antagonist in seasonal AR in a real-life setting. Setipiprant dose-related efficacy in the Phase 2 trial was not confirmed during Phase 3. Setipiprant was well tolerated in both studies. Trial registration NCT01241214 and NCT01484119.

Project description:OBJECTIVE:To prospectively assess the efficacy, general safety, and joint safety of fasinumab, an anti-nerve growth factor monoclonal antibody, in osteoarthritis (OA) hip and/or knee pain. METHODS:Patients with moderate-to-severe OA pain (knee or hip) and history of inadequate response or intolerance to analgesics were randomized to receive fasinumab (at 1 mg, 3 mg, 6 mg, or 9 mg) or placebo every 4 weeks over 16 weeks and were followed up to week 36. Efficacy end points were the change from baseline to week 16 in the pain and physical function subscale scores of the Western Ontario and McMaster Universities OA Index (WOMAC), and patient global assessment (PGA) of OA. Joints were monitored at scheduled assessments (by plain film radiography and magnetic resonance imaging) during treatment and follow-up, and if prompted, at the time of active joint symptoms. RESULTS:Of the 421 patients randomized, 342 completed the 36-week study. All doses of fasinumab yielded statistically significant and clinically important reductions in pain compared to placebo (least squares mean difference in WOMAC pain subscale scores at week 16 ranging -0.78 to -1.40), without any clear dose dependence. Physical function and PGA scores improved in parallel. Treatment-emergent adverse event rates were 17% with fasinumab and 10% with placebo, and 4% and 1% of patients, respectively, discontinued treatment. Arthropathies (25 in total, 7% of fasinumab-treated patients and 1% of placebo-treated patients) occurred in a dose-dependent manner, with 2 occurring in patients receiving the lowest dose of fasinumab and 10 in patients receiving the highest dose. Most of the arthropathies (16 of 25) were discovered with scheduled radiographs and not based on symptoms. Destructive arthropathy (in 1 of 337 treated patients) occurred in 1 patient who was receiving 6 mg fasimumab. CONCLUSION:Fasinumab provided improvements in OA pain and function, even in those benefitting little from previous analgesics. The observed benefit-to-risk relationship favors further clinical development to explore the lowest doses of fasinumab in patients with knee or hip OA.

Project description:A 14-week, randomized, double-blind, multicenter, placebo-controlled study of Japanese patients with chronic low back pain (CLBP) who were randomized to either duloxetine 60?mg once daily or placebo.This study aimed to assess the efficacy and safety of duloxetine monotherapy in Japanese patients with CLBP.In Japan, duloxetine is approved for the treatment of depression, diabetic neuropathic pain, and pain associated with fibromyalgia; however, no clinical study of duloxetine has been conducted for CLBP.The primary efficacy measure was the change in the Brief Pain Inventory (BPI) average pain score from baseline to Week 14. Secondary efficacy measures included BPI pain (worst pain, least pain, pain right now), Patient's Global Impression of Improvement, Clinical Global Impressions of Severity, and Roland-Morris Disability Questionnaire, among other measures, and safety and tolerability.In total, 458 patients were randomized to receive either duloxetine (n?=?232) or placebo (n?=?226). The BPI average pain score improved significantly in the duloxetine group compared with that in the placebo group at Week 14 [-2.43?±?0.11 vs. -1.96?±?0.11, respectively; between-group difference (95% confidence interval),?-?0.46 [-0.77 to-0.16]; P?=?0.0026]. The duloxetine group showed significant improvement in many secondary measures compared with the placebo group, including BPI pain (least pain, pain right now) (between-group difference: -1.69?±?0.10, P?=?0.0009; -2.42?±?0.12, P P?=?0.0230, respectively), Patient's Global Impression of Improvement (2.46?±?0.07, P?=?0.0026), Clinical Global Impressions of Severity (-1.46?±?0.06, P?=?0.0019), and Roland-Morris Disability Questionnaire (-3.86?±?0.22, P?=?0.0439). Adverse events occurring at a significantly higher incidence in the duloxetine group were somnolence, constipation, nausea, dizziness, and dry mouth, most of which were mild or moderate in severity and were resolved or improved.Duloxetine 60?mg was effective and well tolerated in Japanese CLBP patients.2.

Project description:Epratuzumab, a monoclonal antibody that targets CD22, modulates B cell signaling without substantial reductions in the number of B cells. The aim of this study was to report the results of 2 phase III multicenter randomized, double-blind, placebo-controlled trials, the EMBODY 1 and EMBODY 2 trials, assessing the efficacy and safety of epratuzumab in patients with moderately to severely active systemic lupus erythematosus (SLE).Patients met ?4 of the American College of Rheumatology revised classification criteria for SLE, were positive for antinuclear antibodies and/or anti-double-stranded DNA antibodies, had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of ?6 (increased disease activity), had British Isles Lupus Assessment Group 2004 index (BILAG-2004) scores of grade A (severe disease activity) in ?1 body system or grade B (moderate disease activity) in ?2 body systems (in the mucocutaneous, musculoskeletal, or cardiorespiratory domains), and were receiving standard therapy, including mandatory treatment with corticosteroids (5-60 mg/day). BILAG-2004 grade A scores in the renal and central nervous system domains were excluded. Patients were randomized 1:1:1 to receive either placebo, epratuzumab 600 mg every week, or epratuzumab 1,200 mg every other week, with infusions delivered for the first 4 weeks of each 12-week dosing cycle, for 4 cycles. Patients across all 3 treatment groups also continued with their standard therapy. The primary end point was the response rate at week 48 according to the BILAG-based Combined Lupus Assessment (BICLA) definition, requiring improvement in the BILAG-2004 score, no worsening in the BILAG-2004 score, SLEDAI-2K score, or physician's global assessment of disease activity, and no disallowed changes in concomitant medications. Patients who discontinued the study medication were classified as nonresponders.In the EMBODY 1 and EMBODY 2 trials of epratuzumab, 793 patients and 791 patients, respectively, were randomized, 786 (99.1%) and 788 (99.6%), respectively, received study medication, and 528 (66.6%) and 533 (67.4%), respectively, completed the study. There was no statistically significant difference in the primary end point between the groups, with the week 48 BICLA response rates being similar between the epratuzumab groups and the placebo group (response rates ranging from 33.5% to 39.8%). No new safety signals were identified.In patients with moderate or severely active SLE, treatment with epratuzumab?+?standard therapy did not result in improvements in response rates over that observed in the placebo?+?standard therapy group.

Project description:BackgroundNeck pain (NP) is a common musculoskeletal disorder in primary care that frequently causes discomfort. Non-steroidal anti-inflammatory drugs (NSAIDs) may be used to reduce neck pain and associated inflammation and facilitate earlier recovery. Topical diclofenac diethylamine (DDEA) 1.16% gel is clinically proven to be effective and well tolerated in acute and chronic musculoskeletal conditions, but until now no clinical data existed for its use in acute NP. The aim of this study was to assess the efficacy and safety of DDEA 1.16% gel compared with placebo gel in acute NP.MethodsIn a randomized, double-blind, placebo-controlled study, patients with acute NP (n = 72) were treated with DDEA 1.16% gel (2 g, 4x/day, for 5 days) or placebo. Efficacy assessments included pain-on-movement (POM), pain-at-rest (PAR), functional neck disability index (NDI) and response to treatment (decrease in POM by 50% after 48 h). Adverse events (AEs) were recorded throughout the study.ResultsThe primary outcome, POM at 48 h, was statistically significantly lower with DDEA gel (19.5 mm) vs. placebo (56.9 mm) (p < 0.0001), representing a clinically relevant decrease from baseline (75% vs. 23%, respectively). All POM scores were significantly lower with DDEA gel vs. placebo from 1 h, as were PAR and NDI scores from first assessment (24 h) onwards (all p < 0.0001). Response to treatment was significantly higher with DDEA gel (94.4%) vs. placebo (8.3%) (p < 0.0001). There were no AEs with DDEA gel.ConclusionsDDEA 1.16% gel, which is available over-the-counter, was effective and well tolerated in the treatment of acute neck pain. The tools used to assess efficacy suggest that it quickly reduced neck pain and improved neck function. However, questions remain regarding the comparability and validity of such tools. Further studies will help ascertain whether DDEA 1.16% gel offers an alternative treatment option in this common, often debilitating condition.Trial registrationClinicalTrials.gov identifier: NCT01335724.

Dataset Information

Tanezumab for chronic low back pain: a randomized, double-blind, placebo- and active-controlled, phase 3 study of efficacy and safety.

Publications

Tanezumab for chronic low back pain: a randomized, double-blind, placebo- and active-controlled, phase 3 study of efficacy and safety.

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