Efficacy and safety of stapokibart (CM310) in uncontrolled seasonal allergic rhinitis (MERAK): an investigator-initiated, placebo-controlled, randomised, double-blind, phase 2 trial.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhang Y
PROVIDER: S-EPMC10864214 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
Publications
Efficacy and safety of stapokibart (CM310) in uncontrolled seasonal allergic rhinitis (MERAK): an investigator-initiated, placebo-controlled, randomised, double-blind, phase 2 trial.
Zhang Yuan Y Yan Bing B Zhu Zehua Z Wang Xueyan X Song Xicheng X Zhu Dongdong D Ma Tingting T Zhang Yu Y Meng Cuida C Wang Guangke G Wang Chengshuo C Zhang Luo L
EClinicalMedicine 20240206
<h4>Background</h4>There is no trial to assess the benefits of periodically using biologics during the pollen season in patients with uncontrolled seasonal allergic rhinitis (SAR), who have moderate-to-severe symptoms even after standard-of-care. This trial aimed to evaluate the efficacy and safety of the add-on administration of stapokibart, a humanised monoclonal antibody that targets interleukin-4 receptor alpha, in patients with uncontrolled SAR.<h4>Methods</h4>In this investigator-initiated ...[more]
Similar Datasets
Project description:BackgroundSeasonal Allergic Rhinitis is characterised by inflammation of the nasal mucosa upon exposure to common aeroallergens, affecting up to 20-25 % of the population. For those patients whose symptoms are not controlled by standard medical treatment, allergen specific immunotherapy is a therapeutic alternative. Although several studies have shown changes in immunologic responses as well as long term tolerance following treatment with a sublingual allergy immunotherapy tablet, a detailed time course of the early mechanistic changes of local and systemic T and B cell responses and the effects on B cell repertoire in the nasal mucosa have not been fully examined.Methods/designThis is a randomized, double-blind, single-centre, placebo controlled, two arm time course study based in the United Kingdom comparing sublingual allergy immunotherapy tablet (GRAZAX(®), ALK-Abello Horsholm, Denmark) plus standard treatment with placebo plus standard treatment. Up to 50 moderate to severe grass pollen allergic participants will be enrolled to ensure randomisation of at least 44. Further, we shall enrol 20 non-atopic volunteers. Screening will be completed before eligible atopic participants are randomised to one of the two treatment arms in a 1 to 1 ratio. The primary endpoint will be the total nasal symptom score assessed over 60 min following grass pollen nasal allergen challenge after 12 months of treatment. Clinical assessments and/or mechanistic analyses on blood, nasal fluid, brushing and biopsies will be performed at baseline at 1, 2, 3, 4 (coinciding with the peak pollen season), 6 and 12 months of treatment. After 12 months of treatment, unblinding will take place. Those atopic participants receiving active treatment will continue therapy for another 12 months followed by a post treatment phase of 12 months. Assessments and collection of biologic samples from these participants will take place again at 24 and at 36 months from the start of treatment. The 20 healthy, non-atopic controls will undergo screening and one visit only coinciding with the 12 month visit for the atopic participants.DiscussionThe trial will end in April 2017. The trial is registered with ClinicalTrials.gov and the trial identifying number is NCT02005627.Trial registrationPrimary Registry: ClinicalTrials.gov, Trial Identifying number: NCT02005627, Secondary identifying numbers: EudraCT number: 2013-003732-72 REC: 13/EM/0351, Imperial College London (Sponsor): 13IC0847, Protocol Version 6.0, Date: 16.05.2014.
| S-EPMC4682243 | biostudies-literature
Project description:ObjectivesC-C-chemokine receptors (CCRs) are expressed on a variety of immune cells and play an important role in many immune processes, particularly leukocyte migration. Comprehensive preclinical research demonstrated CCR2/CCR5-dependent pathways as pivotal for the pathophysiology of severe COVID-19. Here we report human data on use of a chemokine receptor inhibitor in patients with COVID-19.MethodsInterim results of a 2:1 randomised, placebo-controlled, investigator-initiated trial on the CCR2/CCR5-inhibitor Cenicriviroc (CVC) 150 mg BID orally for 28 d in hospitalised patients with moderate to severe COVID-19 are reported. The primary endpoint is the subject's responder status defined by achieving grade 1 or 2 on the 7-point ordinal scale of clinical improvement on day 15.ResultsOf the 30 patients randomised, 18 were assigned to receive CVC and 12 to placebo. Efficient CCR2- and CCR5 inhibition was demonstrated through CCL2 and CCL4 elevation in CVC-treated patients (485% and 80% increase on day 3 compared to the baseline, respectively). In the modified intention-to-treat population, 82.4% of patients (14/17) in the CVC group met the primary endpoint, as did 91.7% (11/12) in the placebo group (OR = 0.5, 95% CI = 0.04-3.41). One patient treated with CVC died of progressive acute respiratory distress syndrome, and the remaining had a favourable outcome. Overall, treatment with CVC was well tolerated, with most adverse events being grade I or II and resolving spontaneously.ConclusionsOur interim analysis provides proof-of-concept data on CVC for COVID-19 patients as an intervention to inhibit CCR2/CCR5. Further studies are warranted to assess its clinical efficacy.
| S-EPMC9780636 | biostudies-literature
Project description:BackgroundIn patients with COVID-19, granulocyte-macrophage colony stimulating factor (GM-CSF) might be a mediator of the hyperactive inflammatory response associated with respiratory failure and death. We aimed to evaluate whether mavrilimumab, a monoclonal antibody to the GM-CSF receptor, would improve outcomes in patients with COVID-19 pneumonia and systemic hyperinflammation.MethodsThis investigator-initiated, multicentre, double-blind, randomised trial was done at seven hospitals in the USA. Inclusion required hospitalisation, COVID-19 pneumonia, hypoxaemia, and a C-reactive protein concentration of more than 5 mg/dL. Patients were excluded if they required mechanical ventilation. Patients were randomly assigned (1:1) centrally, with stratification by hospital site, to receive mavrilimumab 6 mg/kg as a single intravenous infusion, or placebo. Participants and all clinical and research personnel were masked to treatment assignment. The primary endpoint was the proportion of patients alive and off supplemental oxygen therapy at day 14. The primary outcome and safety were analysed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04399980, NCT04463004, and NCT04492514.FindingsBetween May 28 and Sept 15, 2020, 40 patients were enrolled and randomly assigned to mavrilimumab (n=21) or placebo (n=19). A trial of 60 patients was planned, but given slow enrolment, the study was stopped early to inform the natural history and potential treatment effect. At day 14, 12 (57%) patients in the mavrilimumab group were alive and off supplemental oxygen therapy compared with nine (47%) patients in the placebo group (odds ratio 1·48 [95% CI 0·43-5·16]; p=0·76). There were no treatment-related deaths, and adverse events were similar between groups.InterpretationThere was no significant difference in the proportion of patients alive and off oxygen therapy at day 14, although benefit or harm of mavrilimumab therapy in this patient population remains possible given the wide confidence intervals, and larger trials should be completed.FundingKiniksa Pharmaceuticals.
| S-EPMC7969143 | biostudies-literature
Project description:BackgroundSeasonal-allergic-rhinitis (hay fever) affects approximately 4.6 million (20%) Australians each year. Hay fever manifests as runny/blocked nose and often itchy/sore/swollen eyes, with symptoms greatly impacting the quality of life. Rescue medications such as antihistamines are often needed to restore function, but they may trigger some other unwanted side effects. Probiotics have shown promise to reduce hay fever symptoms.ObjectiveIn this randomized double-blind placebo-controlled 12-week trial, we aimed to assess the tolerability and efficacy of the probiotic formula "NC-Seasonal-Biotic" on symptoms, quality-of-life, and immunological and microbial factors.MethodsAdults, who had previously suffered from hay fever symptoms, were screened for eligibility and randomly allocated to probiotic or placebo trial powder. Treatment effectiveness was assessed by questionnaires, daily total-nasal-symptom-score, and weekly rhinoconjunctivitis quality-of-life questionnaire. Secondary outcome measures included immunological parameters such as T-cell immunity (Th1/Th2 ratio) and the stool-microbiome analysis. Tolerability was assessed weekly by the gastrointestinal symptom scale.ResultsRecruitment and follow-up were challenging around the 2020/2021 hay fever season in Melbourne, Australia, due to the harsh COVID-19 restrictions and extended lockdowns. Out of the 82 adults enrolled in this study, 75% participated (n = 60), and half (n = 40) completed the 10-12-week intervention period. In the intention-to-treat analysis, no significant differences in hay fever symptoms were apparent between the groups, while quality-of-life trended toward greater improvement in the active group. Intention-to-treat analysis was confounded due to a third of all participants not completing the full 10-12-week-intervention period. Subgroup analyses of the participants (n = 40) completing the full 10-12-week study period revealed a significantly greater reduction in symptoms in the active group compared with the placebo group, including runny nose (p = 0.04) and itchy eyes (p = 0.01). Furthermore, the active group reported significant improvements in the quality-of-life, including more functionality during the day (p = 0.05), better sleep (p = 0.005), less fatigue (p = 0.04), less thirst (p = 0.007), and less irritability (p = 0.007). Immunological parameters, measured by T-helper cell ratio (Th1/Th2), improved significantly in the active group compared with the placebo group. Most microbial changes were not statistically different between the groups. The trial powder was generally well tolerated.ConclusionOur study suggests the probiotic formula "NC-Seasonal-Biotic," taken for 10-12 weeks, as effective in reducing hay fever symptoms, such as runny nose and itchy eyes, and improved the quality-of-life and immunological parameters while being well tolerated.Clinical trial registration[www.ClinicalTrials.gov], identifier [ACTRN126200 01078943].
| S-EPMC9169690 | biostudies-literature
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.
| S-EPMC5379543 | biostudies-literature
Project description: Not available
| S-EPMC10633784 | biostudies-literature
Project description:BackgroundInhibition of interleukin (IL)-1 represents a promising treatment option in adult-onset Still's disease (AOSD).ObjectiveTo investigate the efficacy and safety of canakinumab in patients with AOSD and active joint involvement by means of a multicentre, double-blind, randomised, placebo-controlled trial.MethodsPatients with AOSD and active joint involvement (tender and swollen joint counts of ≥4 each) were treated with canakinumab (4 mg/kg, maximum 300 mg subcutaneous every 4 weeks) or placebo. The primary endpoint was the proportion of patients with a clinically relevant reduction in disease activity at week 12 as determined by the change in disease activity score (ΔDAS28>1.2).ResultsAt enrolment, patients had high active disease with a mean DAS28(ESR) of 5.4 in the canakinumab and 5.3 in the placebo group, respectively. In the intention-to-treat analysis, 12 patients (67%) in the canakinumab group and 7 patients (41%) in the placebo group fulfilled the primary outcome criterion (p=0.18). In the per-protocol analysis, significantly higher American College of Rheumatology (ACR) 30% (61% vs 20%, p=0.033), ACR 50% (50% vs 6.7%, p=0.009) and ACR 70% (28% vs 0%, p=0.049) response rates were observed in the canakinumab group compared with the placebo group. Two patients in the canakinumab group experienced a serious adverse event.ConclusionAlthough the study was terminated prematurely and the primary endpoint was not achieved, treatment with canakinumab led to an improvement of several outcome measures in AOSD. The overall safety findings were consistent with the known profile of canakinumab. Thus, our data support indication for IL-1 inhibition with canakinumab in AOSD.
| S-EPMC7392486 | biostudies-literature
Project description:Hand osteoarthritis (OA) is a condition characterised by cartilage degradation and frequently erosive changes. Analgesics and non-steroidal anti-inflammatory drugs are used for symptomatic relief but are often poorly tolerated or contraindicated. Previous publications suggest hydroxychloroquine (HCQ) as a possible treatment for hand OA. The OA-TREAT study aimed to investigate the efficacy and safety of HCQ in patients with inflammatory and erosive hand OA (EOA). OA-TREAT was an investigator-initiated, multicentre, randomised, double-blind, placebo (PBO)-controlled trial. Patients with inflammatory and EOA, according to the ACR criteria, with radiographically erosive disease were randomised 1:1 to HCQ 200-400 mg/day or PBO for 52 weeks (W52). Both groups received stable standard therapy. The primary endpoint was Australian Canadian Hand Osteoarthritis Index (AUSCAN) for pain and hand disability at W52. 75 patients were randomised to HCQ and 78 to PBO. At W52, mean AUSCAN pain was 26.7 in HCQ and 26.5 in PBO patients (p=0.92). Hand disability measured by AUSCAN function (mean) was 48.1 in HCQ and 51.3 in PBO patients (p=0.36). Changes in radiographic scores did not differ significantly (p>0.05) between treatment groups. There were 7 serious adverse events in the HCQ and 15 in the PBO group. OA-TREAT is the first large randomised PBO controlled trial focusing on EOA. HCQ was no more effective than PBO for changes in pain, function and radiographic scores in the 52-week period. Overall safety findings were consistent with the known profile of HCQ.
| S-EPMC8256837 | biostudies-literature
Project description:PurposeExposure to particulate matter (PM) is a well-known risk factor in the triggering and exacerbation of allergic airway disease. Indoor environments, where people spend most of their time, are of utmost importance. To assess the effects of air purifiers [equipped with high-efficiency particulate air (HEPA) filters] on allergic rhinitis (AR) in adult patients, we performed a multicenter, randomized, double-blind, and placebo-controlled study.Materials and methodsPatients with house dust mite (HDM)-induced AR were randomly assigned to either active or mockup (placebo) air-purification groups. Two air purifiers (placed in living room and bedroom) were operated for 6 weeks in each home environment. The primary study endpoint was to achieve improvement in AR symptoms and medication scores. Secondary endpoints were to achieve improvement in the quality of life (QoL) and visual analog scale (VAS) scores, as well as in the indoor (bedroom and living room) concentrations of PM2.5 and PM10.ResultsAfter 6 weeks of air purifier use, medication scores improved significantly in the active (vs. placebo) group, although subjective measures (symptoms, VAS, and QoL scores) did not differ. Bedroom PM2.5 concentrations initially exceeded living room or outdoor levels, but declined (by up to 51.8%) following active purifier operation. Concentrations of PM2.5 in living room and PM10 in bedroom and living room were also significantly reduced through active purification.ConclusionThe use of air purifiers with HEPA filters significantly reduced medication requirements for patients with HDM-induced AR and significantly lowered indoor PM2.5 concentrations, regardless of room placement. Active intervention to reduce household air pollutants may help improve allergic airway disease (clinicaltrials.gov NCT03313453).
| S-EPMC7393300 | biostudies-literature
Project description:ObjectiveT cells play a key role in the pathogenesis of early systemic sclerosis. This study was undertaken to assess the safety and efficacy of abatacept in patients with diffuse cutaneous systemic sclerosis (dcSSc).MethodsIn this 12-month, randomized, double-blind, placebo-controlled trial, participants were randomized 1:1 to receive either subcutaneous abatacept 125 mg or matching placebo, stratified by duration of dcSSc. Escape therapy was allowed at 6 months for worsening disease. The coprimary end points were change in the modified Rodnan skin thickness score (MRSS) compared to baseline and safety over 12 months. Differences in longitudinal outcomes were assessed according to treatment using linear mixed models, with outcomes censored after initiation of escape therapy. Skin tissue obtained from participants at baseline was classified into intrinsic gene expression subsets.ResultsAmong 88 participants, the adjusted mean change in the MRSS at 12 months was -6.24 units for those receiving abatacept and -4.49 units for those receiving placebo, with an adjusted mean treatment difference of -1.75 units (P = 0.28). Outcomes for 2 secondary measures (Health Assessment Questionnaire disability index and a composite measure) were clinically and statistically significantly better with abatacept. The proportion of subjects in whom escape therapy was needed was higher in the placebo group relative to the abatacept group (36% versus 16%). In the inflammatory and normal-like skin gene expression subsets, decline in the MRSS over 12 months was clinically and significantly greater in the abatacept group versus the placebo group (P < 0.001 and P = 0.03, respectively). In the abatacept group, adverse events occurred in 35 participants versus 40 participants in the placebo group, including 2 deaths and 1 death, respectively.ConclusionIn this phase II trial, abatacept was well-tolerated, but change in the MRSS was not statistically significant. Secondary outcome measures, including gene expression subsets, showed evidence in support of abatacept. These data should be confirmed in a phase III trial.
| S-EPMC6935399 | biostudies-literature