Dataset Information

Efficacy and safety of mepolizumab in hypereosinophilic syndrome: A phase III, randomized, placebo-controlled trial.

ABSTRACT:

Background

Anti-IL-5 therapy is a potential treatment for patients with hypereosinophilic syndrome (HES), although its clinical efficacy is unclear.

Objective

We sought to investigate the clinical efficacy and safety of mepolizumab versus placebo in patients with HES.

Methods

This randomized, multicenter, double-blind, placebo-controlled, phase III trial was conducted across 39 centers in 13 countries. Eligible patients had FIP1L1-PDGFRA-negative HES, experienced 2 or more flares (worsening of HES-related symptoms or blood eosinophil count requiring therapeutic escalation) in the previous 12 months, and had a screening blood eosinophil count greater than or equal to 1000 cells/μL. Patients were randomized (1:1) to subcutaneous mepolizumab (300 mg) or placebo every 4 weeks for 32 weeks, plus existing HES therapy. The primary outcome was the proportion of patients with 1 or more flares (worsening of HES-related symptoms necessitating therapy escalation or ≥2 courses of blinded rescue oral corticosteroids) during the study; in addition, patients who withdrew early from the study were counted as having a flare. Safety end points were also assessed.

Results

The proportion of patients experiencing 1 or more flares/withdrawing from the study was 50% lower with mepolizumab versus placebo (15 of 54 [28%] vs 30 of 54 [56%]; P = .002). Logistic regression analysis was consistent with the primary analysis (odds ratio, 0.28; 95% CI, 0.12-0.64; P = .003). Similar proportions of patients in the mepolizumab and placebo groups experienced on-treatment adverse events (48 of 54 [89%] vs 47 of 54 [87%]).

Conclusions

Compared with placebo, mepolizumab significantly reduced the occurrence of flares in patients with HES, with no new safety signals identified.

SUBMITTER: Roufosse F

PROVIDER: S-EPMC9579892 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy and safety of mepolizumab in hypereosinophilic syndrome: A phase III, randomized, placebo-controlled trial.

Roufosse Florence F Kahn Jean-Emmanuel JE Rothenberg Marc E ME Wardlaw Andrew J AJ Klion Amy D AD Kirby Suyong Yun SY Gilson Martyn J MJ Bentley Jane H JH Bradford Eric S ES Yancey Steven W SW Steinfeld Jonathan J Gleich Gerald J GJ

The Journal of allergy and clinical immunology 20200918 6

<h4>Background</h4>Anti-IL-5 therapy is a potential treatment for patients with hypereosinophilic syndrome (HES), although its clinical efficacy is unclear.<h4>Objective</h4>We sought to investigate the clinical efficacy and safety of mepolizumab versus placebo in patients with HES.<h4>Methods</h4>This randomized, multicenter, double-blind, placebo-controlled, phase III trial was conducted across 39 centers in 13 countries. Eligible patients had FIP1L1-PDGFRA-negative HES, experienced 2 or more ...[more]

PMID: 32956756

Similar Datasets

Project description:ObjectiveTo 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.MethodsPatients 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.ResultsOf 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.ConclusionFasinumab 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:IntroductionDermatomyositis (DM) is an inflammatory myopathy characterized by distinct skin manifestations and muscle weakness. Intravenous immunoglobulin (IVIg) has been used off-label as adjuvant therapy in DM, but is not indicated for DM, due to lack of proven efficacy in a large randomized controlled trial. The objective of the ProDERM (Progress in DERMatomyositis) study was to evaluate the efficacy, safety and long-term tolerability of IVIg (Octagam 10%) in patients with DM in a randomized, placebo-controlled, double-blind, Phase III study.MethodsAdult patients with active DM who were continuing standard therapy at a stable dose were eligible for this study. Patients were randomized 1:1 to receive either 2 g/kg of IVIg or placebo, administered every 4 weeks until week 16 (First Period). Patients were switched to the alternate treatment if they showed clinical deterioration in the First Period. After response assessment at week 16, all patients on placebo and those without deterioration on IVIg entered the open-label Extension Period, receiving 2 g/kg IVIg every 4 weeks for 24 weeks.ResultsThe primary efficacy endpoint was the proportion of responders in the IVIg vs placebo arm at week 16, where response was defined per 2016 ACR/EULAR Myositis Response Criteria of at least minimal improvement [Total Improvement Score (TIS) ≥20] and without deterioration at 2 consecutive visits up to week 16. TIS consists of composite response criteria, combining weighted improvement in 6 core set measures (CSMs), Global Disease Activity (Physician and Patient), manual muscle testing-8 (MMT-8), Health Assessment Questionnaire, extra-muscular disease activity, and muscle enzymes. Secondary endpoints included the mean change in individual CSMs, time to improvement in TIS, time to confirmed deterioration in the First Period, and the overall proportion of patients with deteriorations. Adverse events, including infusion reactions and thromboembolic events, were recorded.ConclusionsThe ProDERM study was the first to assess the long-term efficacy and safety of IVIg (Octagam 10%) in a placebo-controlled, blinded, randomized trial in DM. The study aimed to inform on the use of IVIg in the treatment of DM, and results are expected in Q3 2020.Clinicaltrialsgov identifierNCT02728752.

Project description:Study objectivesTo evaluate the efficacy and safety of Dimdazenil, a novel partial positive allosteric modulator for GABAA receptor in adults with insomnia disorder.MethodsThis was a 2-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III study of Dimdazenil. The primary efficacy outcome was total sleep time (TST) analyzed by polysomnography (PSG) on day 13/14. Latency to persistent sleep (LPS), sleep efficiency (SE), and wake after sleep onset (WASO) were analyzed in the same way by polysomnography (PSG). The other secondary outcomes including the average subjective sleep latency (sSL), subjective TST (sTST), subjective SE (sSE), subjective WASO (sWASO), and subjective number of awakenings (sNAW) were analyzed from sleep diary data, and the insomnia severity index (ISI) was also assessed. Treatment-emergent adverse events (TEAEs) were monitored throughout the study.ResultsA total of 546 participants with insomnia (age ≥18 years) were randomized (2:1), received treatment with an oral dose of Dimdazenil (2.5 mg) or placebo, and analyzed. Compared to baseline and placebo, Dimdazenil demonstrated significant improvements in PSG measures, increased TST (71.09, 31.68 minutes, respectively; both p < 0.001), increased SE (13.26%, 5.55%, respectively; both < 0.001), reduced WASO (49.67, 20.16 minutes, respectively; both p < 0.001), and reduced LPS (21.65 minutes, p < 0.001; 6.46 minutes, p = 0.023). Compared to placebo, Dimdazenil also improved key self-reported measures of sTST (18.33 minutes, p < 0.001), sWASO (14.60 minutes, p < 0.001), sSL (4.23 minutes, p < 0.001), sSE (2.97%, p < 0.001), and sNAW (0.29, p < 0.001). Participants treated with Dimdazenil reported a significant improvement in ISI. Dimdazenil was well tolerated. The majority of TEAEs were mild or moderate. There were no clinically relevant treatment-related serious AEs and no deaths.ConclusionsDimdazenil of 2.5 mg provided significant benefit on sleep maintenance and sleep onset in individuals with insomnia disorder versus placebo, with a favorable safety profile and was well tolerated.Clinical trial informationA multicenter, randomized, double-blind phase III clinical study evaluating the efficacy and safety of EVT201 capsules compared to placebo in patients with insomnia disorders (http://www.chinadrugtrials.org), with the number of CTR20201068.

Dataset Information

Efficacy and safety of mepolizumab in hypereosinophilic syndrome: A phase III, randomized, placebo-controlled trial.

Background

Objective

Methods

Results

Conclusions

Publications

Efficacy and safety of mepolizumab in hypereosinophilic syndrome: A phase III, randomized, placebo-controlled trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets