scholarly journals Evaluation of injection-site-related adverse events with galcanezumab: a post hoc analysis of Phase 3 studies in participants with migraine

2020 ◽  
Author(s):  
Virginia L. Stauffer ◽  
Shufang Wang ◽  
Jo Bonner ◽  
ByungKun Kim ◽  
Rohit Bhandari ◽  
...  
Keyword(s):  
Injection Site ◽  
Injection Site Reaction ◽  
Treatment Phase ◽  
Site Reaction ◽  
Open Label ◽  
Double Blind ◽  
Exposure Analysis ◽  
Injection Site Reactions ◽  
Post Hoc ◽  
Site Pain

Abstract Background: Injection-site reactions have been reported with biologicals. In this post hoc analysis of Phase 3 studies in participants with migraine, we provide a comprehensive overview and detailed summary of injection-site reaction with galcanezumab. Methods: Data were obtained from two randomised clinical studies in participants with episodic migraine (EVOLVE-1 and EVOLVE-2), one randomised study in participants with chronic migraine (REGAIN) and one open-label study (Study CGAJ) in participants with episodic or chronic migraine. The injection-site reactions were measured for two different cohorts: 1) six-month double-blind treatment phase in the EVOLVE-1 and EVOLVE-2 studies and three-month double-blind treatment phase in the REGAIN study, where participants received placebo and galcanezumab (placebo-controlled analysis set); 2) three month double-blind (Month 0 to Month 3; 1:1:placebo:galcanezumab) + nine months open-label extension phase (Month 3 to Month 12) of REGAIN and twelve month open-label phase of Study CGAJ, where participants received only galcanezumab (galcanezumab exposure analysis set).Results: A total of 477 participants in the placebo-controlled analysis set (galcanezumab 240 mg, 166/730 [22.7%]; galcanezumab 120 mg, 128/705 [18.2%]; placebo, 183/1451 [12.6%]) reported at least one injection-site reaction. Most of the injection-site reactions were reported as injection-site pain, unspecified injection-site reaction, injection-site erythema, and injection-site pruritus. The incidence of injection-site pain was highest among all reported Injection-site reactions and were reported with similar frequency by participants receiving galcanezumab (galcanezumab 120mg, 10.1%; galcanezumab 240 mg, 11.6%) and placebo (9.5%) and was the most common injection-site reaction reported within 60 minutes of injection (~86% of participants). The frequency of unspecified injection-site reaction, injection-site erythema and injection-site pruritus was significantly (P<0.001) higher in participant receiving galcanezumab versus placebo. In the galcanezumab exposure analysis set participants received up to 12 doses and the frequency of injection-site reactions reported for both doses combined was 21.8%. The reporting of injection-site reactions did not increase with the number of doses received. No ISR-related serious adverse events were reported in both the placebo-controlled and galcanezumab exposure analysis sets.Conclusions: The most common adverse event of galcanezumab is injection-site reactions. However, these events were generally mild-to-moderate in severity, non-serious, resolved spontaneously, and discontinuations due to injection-site reactions were low (1%).

scholarly journals Evaluation of injection-site-related adverse events with galcanezumab: a post hoc analysis of Phase 3 studies in participants with migraine

2020 ◽  
Author(s):  
Virginia Stauffer ◽  
Shufang Wang ◽  
Jo Bonner ◽  
ByungKun Kim ◽  
Rohit Bhandari ◽  
...  
Keyword(s):  
Injection Site ◽  
Injection Site Reaction ◽  
Treatment Phase ◽  
Site Reaction ◽  
Open Label ◽  
Double Blind ◽  
Exposure Analysis ◽  
Injection Site Reactions ◽  
Post Hoc ◽  
Site Pain

Abstract Background: Injection-site reactions have been reported with biologicals. In this post hoc analysis of Phase 3 studies in participants with migraine, we provide a comprehensive overview and detailed summary of injection-site reaction with galcanezumab.Methods: Data were obtained from two randomised clinical studies in participants with episodic migraine (EVOLVE-1 and EVOLVE-2), one randomised study in participants with chronic migraine (REGAIN) and one open-label study (Study CGAJ) in participants with episodic or chronic migraine. The injection-site reactions were measured for two different cohorts: 1) six-month double-blind treatment phase in the EVOLVE-1 and EVOLVE-2 studies and three-month double-blind treatment phase in the REGAIN study, where participants received placebo and galcanezumab (placebo-controlled analysis set); 2) three month double-blind (Month 0 to Month 3; 1:1:placebo:galcanezumab) + nine months open-label extension phase (Month 3 to Month 12) of REGAIN and twelve month open-label phase of Study CGAJ, where participants received only galcanezumab (galcanezumab exposure analysis set).Results: A total of 477 participants in the placebo-controlled analysis set (galcanezumab 240 mg, 166/730 [22.7%]; galcanezumab 120 mg, 128/705 [18.2%]; placebo, 183/1451 [12.6%]) reported at least one injection-site reaction. Most of the injection-site reactions were reported as injection-site pain, unspecified injection-site reaction, injection-site erythema, and injection-site pruritus. The incidence of injection-site pain was highest among all reported Injection-site reactions and were reported with similar frequency by participants receiving galcanezumab (galcanezumab 120mg, 10.1%; galcanezumab 240 mg, 11.6%) and placebo (9.5%) and was the most common injection-site reaction reported within 60 minutes of injection (~86% of participants). The frequency of unspecified injection-site reaction, injection-site erythema and injection-site pruritus was significantly (P<0.001) higher in participant receiving galcanezumab versus placebo. In the galcanezumab exposure analysis set participants received up to 12 doses and the frequency of injection-site reactions reported for both doses combined was 21.8%. The reporting of injection-site reactions did not increase with the number of doses received. No ISR-related serious adverse events were reported in both the placebo-controlled and galcanezumab exposure analysis sets.Conclusions: The most common adverse event of galcanezumab is injection-site reactions. However, these events were generally mild-to-moderate in severity, non-serious, resolved spontaneously, and discontinuations due to injection-site reactions were low (1%).Trial registration: Clinicaltrials.gov identifier: NCT02614183, NCT02614196, NCT02614261, NCT02614287.

scholarly journals Galcanezumab in chronic migraine

Neurology ◽  
2018 ◽  
Vol 91 (24) ◽  
pp. e2211-e2221 ◽  
Author(s):  
Holland C. Detke ◽  
Peter J. Goadsby ◽  
Shufang Wang ◽  
Deborah I. Friedman ◽  
Katherine J. Selzler ◽  
...  
Keyword(s):  
Injection Site ◽  
Chronic Migraine ◽  
Injection Site Reaction ◽  
Treatment Phase ◽  
Preventive Treatment ◽  
Controlled Study ◽  
Open Label ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo

ObjectiveTo evaluate the efficacy and safety of galcanezumab, a humanized monoclonal antibody that selectively binds to calcitonin gene-related peptide, in the preventive treatment of chronic migraine.MethodsA phase 3, randomized, double-blind, placebo-controlled study of LY2951742 in patients with chronic migraine (Evaluation of Galcanezumab in the Prevention of Chronic Migraine [REGAIN]) was a phase 3 study with a 3-month double-blind, placebo-controlled treatment phase and a 9-month open-label extension. Eligible patients 18 to 65 years of age with chronic migraine were randomized 2:1:1 to monthly subcutaneous injections of placebo (n = 558), galcanezumab 120 mg (with a 240-mg loading dose, n = 278), or galcanezumab 240 mg (n = 277). The primary endpoint was the overall mean change from baseline in the number of monthly migraine headache days (MHDs) during the 3-month double-blind treatment phase.ResultsMean number of monthly MHDs at baseline was 19.4 for the total sample. Both galcanezumab dose groups demonstrated greater overall mean reduction in the number of monthly MHDs compared to placebo (placebo −2.7, galcanezumab 120 mg −4.8, galcanezumab 240 mg −4.6) (p < 0.001 for each dose compared to placebo). There were no clinically meaningful differences between galcanezumab doses and placebo on any safety or tolerability outcome except for a higher incidence of treatment-emergent injection-site reaction (p < 0.01), injection-site erythema (p < 0.001), injection-site pruritus (p < 0.01), and sinusitis (p < 0.05) in the galcanezumab 240-mg group relative to placebo.ConclusionsBoth doses of galcanezumab were superior to placebo in reducing the number of monthly MHDs. Galcanezumab appears efficacious, safe, and well tolerated for the preventive treatment of chronic migraine.ClinicalTrials.gov identifierNCT02614261.Classification of evidenceThis interventional study provides Class I evidence that galcanezumab is superior to placebo in the reduction of the number of monthly MHDs.

scholarly journals PMS36 INJECTION SITE REACTION QUESTIONNAIRE: AN ADEQUATE TOOL FOR MEASURING INJECTION SITE REACTIONS?

2010 ◽  
Vol 13 (3) ◽  
pp. A129
Author(s):  
EH Lee ◽  
E Jutkowitz ◽  
S Parasuraman ◽  
C Derk ◽  
LT Pizzi
Keyword(s):  
Injection Site ◽  
Injection Site Reaction ◽  
Site Reaction ◽  
Injection Site Reactions

scholarly journals An assessment of injection site reaction and injection site pain of 1-month and 3-month long-acting injectable formulations of paliperidone palmitate

2018 ◽  
Vol 54 (4) ◽  
pp. 530-538 ◽  
Author(s):  
Jennifer Kern Sliwa ◽  
Adam Savitz ◽  
Isaac Nuamah ◽  
Maju Mathews ◽  
Srihari Gopal ◽  
...  
Keyword(s):  
Injection Site ◽  
Injection Site Reaction ◽  
Paliperidone Palmitate ◽  
Injection Site Pain ◽  
Site Reaction ◽  
Long Acting ◽  
Site Pain

scholarly journals Successful switching of patients with acute schizophrenia from another antipsychotic to brexpiprazole: comparison of clinicians’ choice of cross-titration schedules in a post hoc analysis of a randomized, double-blind, maintenance treatment study

CNS Spectrums ◽  
2018 ◽  
Vol 24 (5) ◽  
pp. 507-517 ◽  
Author(s):  
Christoph U. Correll ◽  
Lily Shi ◽  
Catherine Weiss ◽  
Mary Hobart ◽  
Anna Eramo ◽  
...  
Keyword(s):  
Adverse Events ◽  
Additional Data ◽  
Treatment Phase ◽  
Open Label ◽  
Double Blind ◽  
Syndrome Scale ◽  
Using Data ◽  
Post Hoc ◽  
Negative Syndrome ◽  
Single Blind

ObjectiveTo compare the tolerability and efficacy of different antipsychotic cross-titration schedules, using data from a brexpiprazole study (Equator; NCT01668797).MethodsPatients with schizophrenia were cross-titrated from other antipsychotics to brexpiprazole monotherapy in a 1–4 week open-label conversion phase, then entered a single-blind brexpiprazole treatment phase. Patients were stratified into four “conversion groups,” according to the amount of time spent in the conversion phase. Discontinuation rates, treatment-emergent adverse events (TEAEs), and efficacy (Positive and Negative Syndrome Scale [PANSS]) were compared between conversion groups.ResultsOf the 404 patients treated with brexpiprazole, the majority (72.0%) spent 22–33 days in the conversion phase. Discontinuation rates due to lack of efficacy or adverse events were low in all conversion groups. Of the 292 patients who successfully switched and completed 8 weeks of brexpiprazole treatment, most were converted to brexpiprazole over 22–33 days (80.1%), and fewer were converted over 1–7 days (2.4%), 8–14 days (6.5%), or 15–21 days (11.0%). The incidence of TEAEs over 8 weeks was lower among those converted over 22–33 days (44.4%) than in other conversion groups (62.5–84.2%), although low patient numbers with shorter conversion times limit the generalizability of this finding. Each conversion group showed comparable improvement in PANSS total score from baseline.ConclusionThe majority of patients were cross-titrated to brexpiprazole over a period of 22–33 days, by investigators’ choice. Additional data on shorter conversions may help clinicians to choose a switching paradigm that best meets their patients’ needs.

Long-term tolerability and nonvascular safety of erenumab, a novel calcitonin gene-related peptide receptor antagonist for prevention of migraine: A pooled analysis of four placebo-controlled trials with long-term extensions

Cephalalgia ◽  
2019 ◽  
Vol 39 (14) ◽  
pp. 1798-1808 ◽  
Author(s):  
Messoud Ashina ◽  
David Kudrow ◽  
Uwe Reuter ◽  
David Dolezil ◽  
Stephen Silberstein ◽  
...  
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Injection Site ◽  
Treatment Phase ◽  
Safety Analysis ◽  
Muscle Spasm ◽  
Cumulative Exposure ◽  
Double Blind ◽  
Injection Site Reactions

Background Efficacy and safety of erenumab have been evaluated in a comprehensive clinical development program resulting in approval for migraine prevention in over 40 countries to date. Methods This integrated safety analysis included four double-blind randomized trials and their extensions (up to three-plus years). Safety endpoints included exposure-adjusted patient incidences of adverse events, serious adverse events, and anti-erenumab antibodies. Results In all, 2375 of the patients randomized across the four studies received at least one dose of erenumab (70 mg or 140 mg), with cumulative exposure of 2641.2 patient-years. Exposure-adjusted adverse event rates during the double-blind treatment phase were similar to placebo, with the exception of injection-site reactions (17.1 vs. 10.8 per 100 patient-years), constipation (7.0 vs. 3.8 per 100 patient-years), and muscle spasm (2.3 vs. 1.2 per 100 patient-years). During the long-term extensions, adverse events reported were similar to those observed during the double-blind treatment phase, and rates of injection site reactions, constipation, and muscle spasm were reported at lower rates than in the double-blind treatment phase. There were two deaths reported, both confounded by pre-existing conditions. Conclusions This pooled safety analysis revealed a favorable and stable adverse event profile over time for erenumab with more than three years of exposure. Trial registration ClinicalTrials.gov NCT01952574, NCT02483585, NCT02456740, NCT02066415, and NCT02174861.

A phase 1b study of personalized neoantigen vaccine plus pembrolizumab in adults with advanced cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2615-2615
Author(s):  
Aaron Miller ◽  
Zeynep Kosaloglu-Yalcin ◽  
Luise Westernberg ◽  
Leslie Montero ◽  
Milad Bahmanof ◽  
...  
Keyword(s):  
T Cell ◽  
Injection Site ◽  
Cell Function ◽  
Injection Site Reaction ◽  
Therapeutic Vaccine ◽  
T Cell Responses ◽  
Patient Specific ◽  
Clinical Activity ◽  
Site Reaction ◽  
Cell Responses

2615 Background: Neoantigens (NeoAg) are key targets for personalized immunotherapy but efficient methods for their systematic identification and therapeutic targeting remain elusive. We developed a methodology to reliably identify and verify somatic alteration-derived neoantigens based on natural T cell responses against them which formed the basis of an individualized therapeutic vaccine strategy. Methods: This is a phase Ib study to assess the immunogenicity, safety and early clinical activity of personalized synthetic long peptides (PSLP) cancer vaccines in combination with pembrolizumab for patients with treatment refractory metastatic solid tumors or PSLP vaccine alone as an adjuvant treatment with patients with no evidence of disease (NED) that incorporates patient-specific NeoAg identified by an HLA-agnostic, functional T-cell assay (see table). Results: At the time of data cutoff, a total of 5 patients had been treated on ARM-A, 5 patients on ARM-C and 2 patients on ARM-D. AES possibly attributed to personalized vaccine (PSLP), or pembrolizumab, or both include: Grade 1: Arthralgia (1); Diarrhea (1); Fever (4); Fatigue (7); Generalized muscle weakness (1); Headache (2); Nausea (1); Confusion (1); Injection site reaction (5); Rash maculo-papular (3); Flu like symptoms (5); Myalgia (1); and Grade 2: Diarrhea (1); Fatigue (1); Hyperhidrosis (1); Hypothyroidism (1); Injection site reaction (1); Proteinuria (1); Renal and Urinary – other (1); and Grade 3: Colitis (1). For the 9 patients with at least 1 radiographic assessment at the time of analysis 6 had a best response of stable disease (SD) and 3 had progressive disease (PD). Immune monitoring of peripheral blood specimens consistently demonstrated that NeoAg-specific T cell responses were enhanced following administration of PSLP vaccine. On-treatment biopsies demonstrated immune-editing with the variant allele frequency of targeted mutations decreasing following administration of the PSLP vaccine. Conclusions: Taken together, these data meet the trial primary endpoint by demonstrating PSLP vaccines targeting NeoAg identified using the HLA-agnostic pipeline augment effector T cell function against these targets. Clinical trial information: NCT02287428. [Table: see text]

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