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A phase 3, long-term, open-label safety study of Galcanezumab in patients with migraine.

ABSTRACT: BACKGROUND:Galcanezumab, a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide, has demonstrated in previous Phase 2 and Phase 3 clinical studies (?6-month of treatment) a reduction in the number of migraine headache days and improved patients' functioning. This study evaluated the safety and tolerability, as well as the effectiveness of galcanezumab for up to 12 months of treatment in patients with migraine. METHODS:Patients diagnosed with episodic or chronic migraine, 18 to 65 years old, that were not exposed previously to galcanezumab, were randomized to receive galcanezumab 120 mg or 240 mg, administered subcutaneously once monthly for a year. Safety and tolerability were evaluated by frequency of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events (AEs) leading to study discontinuation. Laboratory values, vital signs, electrocardiograms, and suicidality were also analyzed. Additionally, overall change from baseline in the number of monthly migraine headache days, functioning, and disability were assessed. RESULTS:One hundred thirty five patients were randomized to each galcanezumab dose group. The majority of patients were female (>?80%) and on average were 42 years old with 10.6 migraine headache days per month at baseline. 77.8% of the patients completed the open-label treatment phase, 3.7% of patients experienced an SAE, and 4.8% discontinued due to AEs. TEAEs with a frequency???10% of patients in either dose group were injection site pain, nasopharyngitis, upper respiratory tract infection, injection site reaction, back pain, and sinusitis. Laboratory values, vital signs, or electrocardiograms did not show anyclinically meaningful differences between galcanezumab dosesOverall mean reduction in monthly migraine headache days over 12 months for the galcanezumab dose groups were 5.6 (120 mg) and 6.5 (240 mg). Level of functioning was improved and headache-related disability was reduced in both dose groups. CONCLUSION:Twelve months of treatment with self-administered injections of galcanezumab was safe and associated with a reduction in the number of monthly migraine headache days. Safety and tolerability of the 2 galcanezumab dosing regimens were comparable. TRIAL REGISTRATION:ClinicalTrials.gov as NCT02614287 , posted November 15, 2015. These data were previously presented as a poster at the International Headache Congress 2017: PO-01-184, Late-Breaking Abstracts of the 2017 International Headache Congress. (2017). Cephalalgia, 37(1_suppl), 319-374.

SUBMITTER: Camporeale A

PROVIDER: S-EPMC6234796 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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A phase 3, long-term, open-label safety study of Galcanezumab in patients with migraine.

Camporeale Angelo A Kudrow David D Sides Ryan R Wang Shufang S Van Dycke Annelies A Selzler Katherine J KJ Stauffer Virginia L VL

BMC neurology 20181109 1

<h4>Background</h4>Galcanezumab, a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide, has demonstrated in previous Phase 2 and Phase 3 clinical studies (≤6-month of treatment) a reduction in the number of migraine headache days and improved patients' functioning. This study evaluated the safety and tolerability, as well as the effectiveness of galcanezumab for up to 12 months of treatment in patients with migraine.<h4>Methods</h4>Patients diagnosed with ...[more]

PMID: 30413151

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Project description:PurposeMigraine can negatively impact patient functioning and quality of life. Here, we report the effects of galcanezumab (GMB), a humanized monoclonal antibody that binds to calcitonin gene-related peptide, on patient-reported outcome (PRO) measures in migraine.MethodsCGAJ was a Phase III, randomized, open-label study (12-month open-label and 4-month post-treatment follow-up) in patients with episodic or chronic migraine. Patients aged 18-65 years with diagnosis of migraine (??4 migraine headache days per month) as defined by International Classification of Headache Disorders (ICHD)-3 beta guidelines were included in the study. Patients were randomized 1:1 with subcutaneous GMB 120 mg (with a loading dose of 240 mg) or GMB 240 mg given once monthly for 12 months. Changes from baseline in PRO measures such as Migraine-Specific Quality of Life Questionnaire v2.1 (MSQ) and Migraine Disability Assessment (MIDAS) were assessed.ResultsA total of 135 patients were randomized to each galcanezumab dose group. Mean (SD) baseline MSQ total scores were 53.85 (20.34) [GMB 120 mg] and 53.69 (18.79) [GMB 240 mg]. For MIDAS, mean (SD) total scores were 45.77 (42.06) [GMB 120 mg] and 53.96 (61.24) [GMB 240 mg]. Within-group mean improvement from baseline on MSQ and MIDAS total scores and all individual item/domain scores were statistically significant for both GMB dose groups, at all-time points during the treatment phase (p?<?0.001). For MSQ domain scores, greatest improvement was observed in the Role function-restrictive (RF-R) domain (overall least squares (LS) mean change?±?SE: 31.55?±?1.20 [GMB 120 mg] and 33.40?±?1.16 [GMB 240 mg]). For MIDAS, the overall LS mean change?±?SE from baseline across the entire 12-month treatment phase in total scores were: -33.58?±?2.11 (GMB 120 mg) and -32.67?±?2.04 (GMB 240 mg).ConclusionGalcanezumab was associated with statistically significant changes from baseline in the PRO measures across the entire 12-month treatment period. These results indicate improved health-related quality of life and decreased disability among patients treated with galcanezumab.

Project description:BackgroundThe phase 3 randomized PERSIST study demonstrated the efficacy and tolerability of galcanezumab, a humanized anti-calcitonin gene-related peptide (CGRP) monoclonal antibody for prevention of episodic migraines. We present findings from the open-label extension (OLE) of PERSIST, which evaluated the long-term efficacy and safety of galcanezumab in patients from China, India, and Russia.MethodsPatients completing the 3-month double-blind period of PERSIST were eligible for the 3-month OLE. Patients previously randomized to galcanezumab (GMB/GMB group) continued to receive galcanezumab 120 mg at all three visits during the OLE whereas patients randomized to placebo received a 240 mg loading dose of galcanezumab and then two 120 mg doses (PBO/GMB group). The primary outcome was the mean change (from double-blind baseline) in the number of monthly migraine headache days (MHDs) to month 6. Other endpoints included percent reduction in monthly MHDs from double-blind baseline to month 6, functional outcomes, safety and tolerability.ResultsOverall, 99% of patients completing the double-blind period entered the OLE, and 96% completed through month 6. Patients in the GMB/GMB group achieved continued improvements in efficacy, with the reduction from baseline in the mean number of monthly MHDs, and slightly increasing from 4.01 days at the end of the double-blind period to 4.62 at the end of the OLE. Of patients who were ≥ 50% responders to galcanezumab at month 3, 66% maintained this response through to month 6. Patients in the PBO/GMB group experienced a rapid reduction in the number of monthly MHDs after initiation of galcanezumab, with a mean reduction from baseline of 4.56 days by month 6. The long-term benefits of galcanezumab were also supported by improvements in other efficacy and functional endpoints. All safety findings were consistent with the known long-term safety profile of galcanezumab; no patients experienced a treatment-related serious adverse event.ConclusionsGalcanezumab was efficacious and well-tolerated in patients with episodic migraine from China, India and Russia, for up to 6 months.Trial registrationClinicalTrisABSTRACT_pals.gov NCT03963232, registered May 24, 2019.

Project description:ObjectiveTo assess long-term (up to 2 years) efficacy, tolerability, and safety of erenumab for the prevention of episodic migraine (EM) in Japanese patients.BackgroundPreviously published results from the double-blind treatment phase (DBTP) of a phase 2 clinical study have demonstrated the efficacy and safety of erenumab in Japanese patients with EM.MethodsPatients completing the 24-week placebo-controlled DBTP could continue into the 76-week open-label treatment phase (OLTP), receiving erenumab 70 mg or 140 mg subcutaneously once monthly. The initial dose in the OLTP was erenumab 70 mg monthly, which was later changed to 140 mg. After study completion, the following were assessed: change from baseline in monthly migraine days (MMD), change from baseline in monthly acute migraine-specific medication days (MSMD), percentage of patients achieving ≥50% and ≥75% reduction in MMD, change from baseline in the 6-item Headache Impact Test (HIT-6™) score, and safety (exposure-adjusted patient-incidence of adverse events [AEs], calculated as number of patients per 100 patient-years).ResultsOf 475 patients enrolled in the DBTP, 459 (96.6%) continued in the OLTP. The mean (SD) MMD was 7.9 (2.3) at baseline with the overall change from baseline at week 100 of -2.9 (4.1) days. The monthly acute MSMD was 5.7 (2.8) at baseline with change from baseline at week 100 of -1.7 (3.7) days. The proportion of patients who achieved ≥50% and ≥75% reduction in MMD from baseline at week 100 was 177/398 (44.5%) and 94/398 (23.6%), respectively. The HIT-6™ score was 58.4 (5.4) at baseline with a change of -6.4 (8.2) at week 100. The exposure-adjusted patient-incidence of AEs during the OLTP was 207.1/100 patient-years for the combined erenumab group, similar to that observed for either erenumab (271.0/100 patient-years) or placebo (257.3/100 patient-years) during the DBTP, and no new safety signals were detected during the OLTP.ConclusionLong-term erenumab treatment in Japanese patients with EM demonstrated sustained efficacy for up to 2 years, with a safety profile similar to previous studies, supporting erenumab as a potential new therapy for EM prevention in Japan.

Project description:IntroductionEarly discontinuation and poor adherence are common limitations of conventional preventive migraine medications that limit their long-term efficacy. Therefore, a migraine preventive medication with favorable long-term safety is warranted.ObjectiveThis study aimed to evaluate the long-term safety and tolerability of fremanezumab for the preventive treatment of chronic or episodic migraine in Japanese patients.MethodsIn this 52-week, randomized, open-label, parallel-group study, fremanezumab monthly or quarterly was administered in newly enrolled Japanese patients with chronic migraine or episodic migraine. Safety was assessed by monitoring of treatment-emergent adverse events, including injection-site reactions, laboratory and vital sign assessments. Newly enrolled patients and rollover patients from previous phase IIb/III trials who did not receive fremanezumab in this study were included in the immunogenicity testing cohort (n = 587). Efficacy outcomes included changes from baseline in the average monthly migraine days and headache days of at least moderate severity. Other efficacy outcomes included changes in disability scores.ResultsA total of 50 patients were enrolled with chronic migraine (monthly, n = 17; quarterly, n = 17) or episodic migraine (monthly, n = 8; quarterly, n = 8). The most commonly reported treatment-emergent adverse events were nasopharyngitis (64.0%) and injection-site reactions (erythema, 24.0%; induration, 10.0%; pain, 8.0%; pruritus, 6.0%). The discontinuation rate was low (4.0% from adverse events, 2.0% from a lack of efficacy) and no deaths were reported. The incidence of anti-drug antibody development was low (2.4%). Fremanezumab reduced monthly migraine days and headache days of at least moderate severity from 1 month after initial administration, and this effect was maintained with no worsening throughout 12 months. Fremanezumab also led to sustained reductions in any acute headache medication use and headache-related disability at 12 months.ConclusionsFremanezumab administered monthly and quarterly was well tolerated in patients with chronic migraine and episodic migraine and led to sustained improvements in monthly migraine days and headache days of at least moderate severity throughout 12 months.Clinical trial registrationClinicalTrials.gov Identifier: NCT03303105.

Project description:ObjectivesTo address the need for long-term lasmiditan data, the GLADIATOR study evaluated the safety (primary) and efficacy (secondary) of lasmiditan for the intermittent, acute treatment of migraine attacks for up to 1 year.MethodsIn this prospective, randomized, open-label, Phase 3 study, patients who had completed either of two single-attack studies were offered the opportunity to be randomized 1:1 to lasmiditan 100 mg or 200 mg. Patients were asked to use lasmiditan as the first treatment for each new migraine attack of at least moderate severity. Assessments occurred at baseline and at prespecified time increments up to 48 hours after each dose of study drug using an electronic diary, and safety was assessed throughout the study. Migraine Disability Assessment (MIDAS) was assessed at each visit.ResultsAs of the cut-off date for this interim analysis (6 March 2018), 1978 patients had received ≥ 1 lasmiditan dose and treated 19,058 migraine attacks. Overall, treatment-emergent adverse events (TEAEs) were similar to those in the single-attack studies and included dizziness (18.6%), somnolence (8.5%), and paresthesia (6.8%). The frequency of TEAEs generally decreased with subsequent attacks. No treatment-related serious adverse events and no cardiovascular TEAEs potentially due to vasoconstriction were observed. For both lasmiditan doses, efficacy measures were generally consistent over study quarters and treated attacks. Overall, across all treated attacks at 2 hours post-dose, pain freedom was observed in 26.9% of the attacks treated with lasmiditan 100 mg and 32.4% of the attacks treated with lasmiditan 200 mg. MIDAS total scores decreased over time.ConclusionsThe interim results of this long-term study showed intermittent lasmiditan (100 mg and 200 mg) to be generally well tolerated and efficacious for the acute treatment of migraine over a 1-year period. Trial registration number: NCT02565186; https://clinicaltrials.gov/ct2/show/NCT02565186.

Project description:Brodalumab, an interleukin-17 receptor A inhibitor, demonstrated rapid and robust efficacy with a favorable safety profile in patients with moderate to severe plaque psoriasis. Here, we present data from a multicenter, open-label extension study in patients with plaque psoriasis with/without psoriatic arthritis who completed 64 weeks of treatment with brodalumab (140 or 210 mg, every 2 weeks [Q2W]). Patients were enrolled to evaluate the long-term safety and efficacy of a modified dose of brodalumab. Eligible patients were switched to a reduced dose of brodalumab (140 mg every 4 weeks on day 1) in the extension study; the dose and dosing interval were modified sequentially at the physician's discretion (minimum 140 mg every 8 weeks and maximum 210 mg Q2W) until drug approval, after which all patients were switched to 210 mg Q2W for postmarketing surveillance. Of the 129 patients enrolled, 107 (82.9%) completed the 108-week or more extension study. All patients had psoriasis that was well controlled with brodalumab treatment on day 1. Improvement in psoriasis-related symptoms, evaluated with the Psoriasis Area and Severity Index, Psoriasis Scalp Severity Index, Dermatology Life Quality Index, Nail Psoriasis Severity Index, and American College of Rheumatology 20, 50 and 70, was maintained during the 108-week extension study. Brodalumab treatment was well tolerated throughout, and no new safety signals were identified. The most commonly reported treatment-related adverse event was nasopharyngitis, followed by influenza and oral candidiasis. No cases of serious candida infection or Crohn's disease were observed in this study. Serious treatment-related adverse events, such as appendicitis, brain abscess, bacterial meningitis, colon cancer, immunoglobulin A nephropathy and tubulointerstitial nephritis, were reported in one patient each. No anti-brodalumab-binding antibodies or brodalumab-neutralizing antibodies were detected in any patient throughout the extension study. Overall, the long-term efficacy and safety of brodalumab were demonstrated over 108 weeks.

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A phase 3, long-term, open-label safety study of Galcanezumab in patients with migraine.

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A phase 3, long-term, open-label safety study of Galcanezumab in patients with migraine.

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