Dataset Information

Galcanezumab in chronic migraine: The randomized, double-blind, placebo-controlled REGAIN study.

ABSTRACT:

Objective

To 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.

Methods

A 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.

Results

Mean 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.

Conclusions

Both 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.

Clinicaltrialsgov identifier

NCT02614261.

Classification of evidence

This interventional study provides Class I evidence that galcanezumab is superior to placebo in the reduction of the number of monthly MHDs.

SUBMITTER: Detke HC

PROVIDER: S-EPMC6329331 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeTo evaluate secondary outcomes including changes in functioning and disability associated with galcanezumab, a humanized monoclonal antibody to calcitonin gene-related peptide, in patients with chronic migraine.MethodsPatients randomly received galcanezumab (120 mg n = 278, 240 mg n = 277) or placebo (n = 558) during 3 months of double-blind treatment, followed by a 9-month open-label extension. The Migraine-Specific Quality-of-Life Questionnaire v2.1 (MSQv2.1) measured the impact of migraine on patient functioning. The Migraine Disability Assessment (MIDAS) quantified headache-related disability. Changes from baseline were analyzed with mixed model repeated measures or analysis of covariance.ResultsTotal MSQ score at baseline was 44.88 ± 18.02 (mean ± SD), indicating significant functional impairment. At Month 3, least squares (LS) mean change ± SE in total MSQ for galcanezumab-treated patients were 20.51 ± 1.49 (120 mg) and 20.49 ± 1.49 (240 mg), both statistically significantly greater vs placebo-treated patients (14.55 ± 1.21; both P < 0.001). Total MIDAS score at baseline was 67.24 ± 57.31 (mean ± SD). At Month 3, LS mean change ± SE from baseline in total MIDAS for galcanezumab-treated patients was statistically significantly greater than placebo for 120 mg group (placebo: - 11.53 ± 3.38 vs 120 mg: - 20.27 ± 4.07; P < 0.05) but not for 240 mg group (- 17.02 ± 4.05). At Month 12, within-group mean changes from baseline for total MSQ (28.56 ± 1.19 previous placebo; 29.53 ± 1.51 previous 120 mg; 25.83 ± 1.49 previous 240 mg) and MIDAS scores (- 28.47 ± 2.95 previous placebo; - 31.47 ± 3.69 previous 120 mg; - 31.13 ± 3.62 previous 240 mg) were statistically significant (P < 0.001) for the open-label treatment population regardless of previous double-blind treatment assignment.ConclusionsGalcanezumab-treated patients with chronic migraine reported statistically significant improvements in functioning and disability, representing a clinically significant change.Trial registrationClinicalTrials.gov registry: NCT02614261. Registered 25 November 2015.

Project description:ObjectiveTo examine the likelihood of response with continued galcanezumab treatment in patients with episodic or chronic migraine without initial clinical improvement.BackgroundA percentage of patients with migraine may require additional time on pharmacotherapy but discontinue treatment prematurely. Additionally, recognizing when continued treatment is unlikely to provide improvement limits unnecessary exposure.MethodsPost hoc analysis of response after continued galcanezumab treatment was conducted in a subset of patients with episodic (N = 879) and chronic (N = 555) migraine who did not achieve "good" early improvement (episodic, ≥50% reduction in baseline migraine headache days [MHD] and chronic, ≥30% reduction) after 1 month of dosing (NR-1; episodic, n = 450 and chronic, n = 306). This subset was categorized by level of reduction in MHD during 1 month of treatment: "modest" (>30% to <50% fewer MHD for episodic and >10% to <30% fewer MHD for chronic), "limited" (episodic only; >10% to ≤30% fewer MHD), or "minimal/no" early improvement (≤10% fewer MHD to ≤10% more MHD), or "worsening" (>10% more MHD). The percentages of patients having "better" (≥75% fewer MHD for episodic and ≥50% for chronic), "good," or "little-to-no" (≤10% fewer MHD) response during the remaining treatment period were calculated for each category. Similarly, the subset of NR-1 patients who did not achieve "good" early improvement after 2 months of treatment (NR-2; episodic, n = 290 and chronic, n = 240) were categorized by level of their average monthly reduction across 1 and 2 months using similar categories.ResultsOf NR-1 patients with episodic migraine having "modest" early improvement, 62% (96/155) achieved "good" and 20% (31/155) achieved "better" responses with continued treatment. A percentage of patients with "limited" (43%; 46/108) or "minimal/no" (34%; 29/85) early improvement, or "worsening" (20%; 20/102) achieved a "good" response after continued treatment. A percentage of NR-1 patients with chronic migraine having "modest" early improvement achieved "good" (38%; 44/116) and "better" (13%; 15/116) responses with continued treatment. A "good" response was achieved for a percentage of patients with "minimal/no" early improvement (17%; 23/133). Similar patterns were observed for the NR-2 subset, though percentages were lower.ConclusionsGalcanezumab-treated patients with episodic or chronic migraine without response following 1 or 2 months of treatment appear to have a reasonable likelihood of continued improvement in months following initial treatment and this opportunity is more likely in patients showing greater early improvements. While a small percentage of patients with episodic or chronic migraine who experienced worsening in the number of MHD following initial treatment responded with continued treatment, most do not show substantial reduction in MHD. Overall benefit of therapy should be determined collaboratively between the patient and physician.

Project description:BACKGROUND:Focus on the frequency of migraine pain may undervalue the total burden of migraine as pain duration and severity may present unique, additive burden. A composite measure of total pain burden (TPB; frequency, severity, and duration) may provide a more comprehensive characterization of pain burden and treatment response in patients with episodic migraine (EM) or chronic migraine (CM). The impact of galcanezumab versus placebo on TPB among patients with EM or CM was analyzed. METHODS:Patients from randomized, double-blind, placebo-controlled episodic (two 6-month studies pooled) and chronic migraine (3-month) studies received once-monthly subcutaneous injection of galcanezumab 120?mg or placebo. A post hoc analysis of TPB for a given month was calculated as severity-weighted duration by multiplying duration (hours) and maximum pain severity (0?=?none, 1?=?mild, 2?=?moderate, 3?=?severe) of migraine for each day and summing these over the days in a month. Least square mean change from baseline in monthly TPB across Months 1-6 (EM, N?=?444 galcanezumab, N?=?894 placebo) and Months 1-3 (CM, N?=?278 galcanezumab, N?=?558 placebo) were compared using a mixed-model repeated measures model. Correlation of the Migraine Specific Quality of Life Questionnaire (MSQ) and Migraine Disability Assessment Scale (MIDAS) to TPB at baseline was assessed. RESULTS:At baseline, the duration of migraine on a given migraine headache day accounted for the greatest unique proportion of variability (EM, 57.4% and CM, 61.1%) to TPB after adjusting for frequency of migraine headache days and maximum pain severity. The decrease from baseline in monthly TPB was greater with galcanezumab than placebo for patients with EM (68.6 versus 36.2) and CM (102.6 versus 44.4). The average percent reduction of TPB from baseline was significantly greater with galcanezumab compared with placebo in patients with EM (50.8% versus 17.2%) and CM (29.7% versus 11.0%). In patients with EM and CM, TPB correlated with MSQ total score (r?=?-?0.35 and r?=?-?0.37) and MIDAS (r?=?0.34 and r?=?0.32). CONCLUSIONS:Greater reduction in TPB was seen in patients with EM and CM treated with galcanezumab 120?mg once-monthly injection relative to placebo. Discussing TPB supports patient-centric conversations regarding treatment expectations when clinicians are evaluating options for migraine prevention. TRIAL REGISTRATION:ClinicalTrials.gov : # NCT02614183 (I5Q-MC-CGAG; EVOLVE-1), # NCT02614196 (I5Q-MC-CGAH; EVOLVE-2), and # NCT02614261 (I5Q-MC-CGAI; REGAIN) - all 3 trials were registered on 23 November 2015.

Project description:BACKGROUND:Maintenance of effect following treatment with galcanezumab compared to placebo in adult patients with episodic or chronic migraine was evaluated. METHODS:In 2 similarly designed studies of patients with episodic migraine (6?months) and 1 study of patients with chronic migraine (3?months), patients randomized in a 1:1:2 ratio received a subcutaneous injection of galcanezumab 120?mg/month (after an initial loading dose of 240?mg) or 240?mg/month or placebo. Maintenance of effect during the double-blind phase was evaluated based on a comparison of the percentages of galcanezumab- and placebo-treated patients with maintenance of 30, 50, 75, and 100% response (defined as ?30, ?50, ?75, and 100% reduction from baseline in monthly migraine headache days [MHD]) at an individual patient level. Logistic regression analyses were used for between treatment comparisons. RESULTS:A total of 1773 adult patients with episodic migraine (n?=?444 for galcanezumab 120?mg; n?=?435 for galcanezumab 240?mg; n?=?894 for placebo for 2 studies pooled) and 1113 patients with chronic migraine (n?=?278 for galcanezumab 120?mg; n?=?277 for galcanezumab 240?mg; n?=?558 for placebo) were evaluated. In patients with episodic migraine, ?50% response was maintained in 41.5 and 41.1% of galcanezumab-treated patients (120?mg and 240?mg, respectively) for ?3 consecutive months (until patient's endpoint) and 19.0 and 20.5%, respectively, for 6 consecutive months and was significantly greater than the 21.4 and 8.0% of placebo-treated patients at ?3 and 6?months consecutively (P?<?0.001). Approximately 6% of galcanezumab-treated patients maintained ?75% response all 6?months versus 2% of placebo-treated patients. Few galcanezumab-treated patients maintained 100% response. In patients with chronic migraine, 29% of galcanezumab-treated patients maintained ?30% response all 3?months compared to 16% of placebo patients while ?50% response was maintained in 16.8 and 14.6% of galcanezumab-treated patients (120?mg and 240?mg) and was greater than placebo (6.3%; p?<?0.001). Few patients maintained ?75% response. CONCLUSIONS:Treatment with galcanezumab 120?mg or 240?mg demonstrated statistically significant and clinically meaningful persistence of effect in patients with episodic migraine (?3 and 6 consecutive months) and in patients with chronic migraine (for 3?months). STUDY IDENTIFICATION AND TRIAL REGISTRATION:Study Identification: EVOLVE-1 (I5Q-MC-CGAG); EVOLVE-2 (I5Q-MC-CGAH); REGAIN (I5Q-MC-CGAI) TRIAL REGISTRATION: ClinicalTrials.gov ; NCT02614183 (EVOLVE-1); NCT02614196 (EVOLVE-2); NCT02614261 (REGAIN).

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