Emgality ® (galkanezumab)

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Emgality® ▼ (galcanezumab): Skäl till avbrott i kliniska fas 3 migränförebyggande prövningar

Studiens slutföringsgrader för galcanezumab-behandlade patienter var >82% och den vanligaste orsaken var att studien avbröts av patienten.

Reasons for Discontinuation

Phase 3 Placebo-Controlled Migraine Prevention Trials

Overview of Phase 3 Randomized, Double-blind, Placebo-controlled Trials

Galcanezumab has been studied in phase 3 randomized, double-blind, placebo-controlled studies in adult patients for the prevention of

  • episodic migraine (EVOLVE-1 and EVOLVE-2),1,2 and

  • chronic migraine (REGAIN).3

The studies had a duration of

  • 6 months for prevention of episodic migraine,1,2 and

  • 3 months for prevention of chronic migraine, with an optional 9-month open-label extension phase.3 

Patients were randomized at the beginning of double-blind treatment in a 2:1:1 ratio to receive monthly subcutaneous injections of 

  • placebo

  • galcanezumab 120 mg with a loading dose of 240 mg, or

  • galcanezumab 240 mg.1-3 

  • The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.4 Please note that the results of a maintenance dose of 240 mg galcanezumab once monthly are also included in this response. Even though this dose has been tested in pivotal studies, it has not been approved and therefore is not recommended.

In these studies, the injections were administered by investigative site personnel using a prefilled syringe.1-3,5

Patient Disposition

Completion rates of the double-blind treatment phase for patients who received galcanezumab were

  • 82.8% and 87.7% for EVOLVE-1 and EVOLVE-2, and

  • 95.3% for REGAIN.1-3

Across all three treatment groups in EVOLVE-1, EVOLVE-2, and REGAIN, the most common reason for study discontinuation was withdrawal by the patient.1-3

Discontinuation was more common in the episodic migraine studies relative to the chronic migraine study. This might be expected given the longer study duration of 6 months for the episodic studies. Otherwise, patient disposition during the double-blind treatment phases was similar across the 3 studies.5

In EVOLVE-1 and EVOLVE-2, 3.58% of placebo-treated patients, and 2.73% of galcanezumab-treated patients discontinued from the double-blind treatment phase due to any reason by Visit 7 (Month 3).5

Completion rates of the double-blind treatment phase and reasons for discontinuation are provided inTable 1.

Table 1. Completion of Double-blind Treatment and Reasons for Discontinuation - EVOLVE-1, EVOLVE-2, and REGAIN1-3,5

Disposition

PBO
N=433
n (%)

GMB 120
N=213
n (%)

GMB 240
N=212
n (%)

PBO
N=461
n (%)

GMB 120
N=231
n (%)

GMB 240
N=223
n (%)

PBO
N=558
n (%)

GMB 120
N=278
n (%)

GMB 240
N=277
n (%)


EVOLVE-1

EVOLVE-2

REGAIN

Completed DB Treatment

351 (81.06)

177 (83.10)

175 (82.55)

387 (83.95)

203 (87.88)

195 (87.44)

508 (91.04)

263 (94.60)

266 (96.03)a

D/C DB phase

82 (18.94) 

36 (16.90)

37 (17.45)

74 (16.05)

28 (12.12)

27 (12.11)b

49 (8.78)c

15 (5.40)

11 (3.97)d

D/C reason

AE

10 (2.31)

9 (4.23)

7 (3.30)

8 (1.74)

5 (2.16)

9 (4.04)

6 (1.08)

3 (1.08)

2 (0.72)

Lack of efficacy

10 (2.31)

1 (0.47)

2 (0.94)

6 (1.30)

1 (0.43)

1 (0.45)

5 (0.90)

0

0

Lost to follow up

18 (4.16)

9 (4.23)

5 (2.36)

10 (2.17)

7 (3.03)

0d

10 (1.79)

4 (1.44)

1 (0.36)

Physician decision

7 (1.62)

3 (1.41)

2 (0.94)

4 (0.87)

0

2 (0.90)

2 (0.36)

1 (0.36)

1 (0.36)

Pregnancy

2 (0.46)

1 (0.47)

3 (1.42)

1 (0.22)

2 (0.87)

0

2 (0.36)

2 (0.72)

0

Protocol deviation

2 (0.46)

2 (0.94)

2 (0.94)

5 (1.08)

2 (0.87)

1 (0.45)

6 (1.08)

1 (0.36)

0

Terminated by sponsor

---

---

---

1 (0.22)

0

0

---

---

---

Withdrawal by patient

33 (7.62)e

11 (5.16)e

16 (7.55)e

39 (8.46)e

11 (4.76)e

14 (6.28)e

13 (3.23)f

4 (1.44)f

7 (2.53)f

Abbreviations: AE = adverse event; DB = double-blind; D/C = discontinued; GMB 120 = galcanezumab 120 mg; GMB 240 = galcanezumab 240 mg; PBO = placebo.

a p<.01 vs placebo.

b In EVOLVE-2, 1 patient randomized to 240 mg discontinued early (lost to follow-up) but because the discontinuation date was reported after the data cutoff date, the patient is not counted among the 27 discontinuations.

c In REGAIN, 1 patient randomized to placebo discontinued early (withdrawal by subject) but because the discontinuation date was reported after the data cut-off date, the patient is not counted among the 49 discontinuations.

d p<.05 vs placebo.

e Reasons for patient decision to discontinue treatment: concerns about study procedures, perceived risks, scheduling conflicts, and patient is relocating or has relocated.

f Reasons for patient decision to discontinue treatment: concern about study procedures/perceived risks, scheduling conflicts, subject is moving or has moved, withdrew consent, family emergency, injection too painful, adverse event, visit not done, traveling abroad.

Note: The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose .4 The results of a maintenance dose of galcanezumab 240 mg once monthly are also described here. Even though this dose has been tested in pivotal studies, it has not been approved and therefore is not recommended.

Phase 3 Open-label Safety Study

Study CGAJ was a phase 3 open-label, 12-month safety study of galcanezumab in 270 patients with episodic or chronic migraine.6

Patients were randomized to receive monthly subcutaneous injections of

  • galcanezumab 120 mg with a loading dose of 240 mg, or

  • galcanezumab 240 mg.6

The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.4

Investigative site personnel administered the galcanezumab loading dose at the first injection visit. The patient or caregiver administered subsequent injections, after reviewing the instructions for self-administration.6,7 Galcanezumab was supplied as an injectable solution in a 1-mL single-dose disposable prefilled syringe or autoinjector.6

Patient Disposition

Overall, 210 patients (77.8%) completed the 12-month open-label treatment period. Reasons for discontinuation are provided in Table 2.6

Table 2. Study Completion Rate and Reasons for Discontinuation - Study CGAJ5,6

Disposition

GMB 120 mg
N=135
n (%)

GMB 240 mg
N=135
n (%)

Study completion

97 (71.9)

113 (83.7)a

D/C

38 (28.1)

22 (16.3)a

D/C reason

AE

7 (5.19)

6 (4.44)

Lack of efficacy

13 (9.63)

5 (3.70)

Lost to follow up

7 (5.19)

4 (2.96)

Physician decision

1 (0.74)

0 (0.0)

Withdrawal by subject

10 (7.41)b

7 (5.19)b

Abbreviations: AE = adverse event; D/C = discontinuation; GMB = galcanezumab.

a p<.05 vs galcanezumab 120 mg.

b Reasons for patient decision to discontinue treatment: concerns about study procedures, perceived risks, scheduling conflicts, and patient is relocating or has relocated.

Note: The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose .4 The results of a maintenance dose of galcanezumab 240 mg once monthly are also described here. Even though this dose has been tested in pivotal studies, it has not been approved and therefore is not recommended.

Therapeutic Indication

Galcanezumab is indicated for the prophylaxis of migraine in adults who have at least 4 migraine days per month.4

The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.4

References

1. Stauffer VL, Dodick DW, Zhang Q, et al. Evaluation of galcanezumab for the prevention of episodic migraine: the EVOLVE-1 randomized clinical trial. JAMA Neurol. 2018;75(9):1080-1088. http://dx.doi.org/10.1001/jamaneurol.2018.1212

2. Skljarevski V, Matharu M, Millen BA, et al. Efficacy and safety of galcanezumab for the prevention of episodic migraine: results of the EVOLVE-2 phase 3 randomized controlled clinical trial. Cephalalgia. 2018;38(8):1442-1454. http://dx.doi.org/10.1177/0333102418779543

3. Detke HC, Goadsby PJ, Wang S, et al. Galcanezumab in chronic migraine: the randomized, double-blind, placebo-controlled REGAIN study. Neurology. 2018;91(24):e2211-e2221. http://dx.doi.org/10.1212/WNL.0000000000006640

4. Emgality [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

5. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

6. Camporeale A, Kudrow D, Sides R, et al. A phase 3, long-term, open-label safety study of galcanezumab in patients with migraine. BMC Neurology. 2018;18(1):188. http://dx.doi.org/10.1186/s12883-018-1193-2

7. Stauffer VL, Sides R, Kielbasa W, Jin Y. Patient-reported experiences with self-injections using prefilled syringe and autoinjector devices in an open-label, long-term study of galcanezumab in patients with migraine. Poster presented at: American Headache Society (AHS) – 60th Annual Meeting; June 28 – July 1, 2018; San Francisco, CA.

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Datum fӧr senaste ӧversyn 2018 M07 03


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