A Randomized, Double-Blind, Placebo-Controlled Study of Galcanezumab in Patients 6 to 17 Years of Age with Episodic Migraine - the REBUILD-1

In this study, galcanezumab is being researched. This study drug is not
registered in the Netherlands for episodic migraine in children and adolescents
The product is approved for the prevention of migraine in adults. It is known
that it is safe and it works for preventing migraine in adults, but it is
unknown if the study drug is safe and works for episodic migraine in children
and adolescents.

This study has been transitioned to CTIS with ID 2023-505836-36-00 check the CTIS register for the current data.

Main Objective:
To demonstrate the superiority of galcanezumab versus placebo in the prevention
of migraine in (at least) 1 of the following populations with migraine: the
overall pediatric population (6 to 17 year-olds) or the adolescent population
(12 to 17 year-olds).

Second Objective:
- To compare galcanezumab with placebo with respect to 50% response rate
- To compare galcanezumab with placebo with respect to 75% response rate
Time to Onset:
* To compare galcanezumab with placebo with respect to:
o the month of onset of effect
o the week of onset of effect within Month 1
o the day of onset of effect within Week 1

-To compare galcanezumab with placebo with respect to change in nausea and/or
vomiting symptoms associated with migraine headache
-To compare galcanezumab with placebo with respect to change in phonophobia and
photophobia symptoms associated with migraine headache

Study CGAS is a multicenter, randomized, double-blind, parallel group,
placebo-controlled trial with 5 study periods in patients 6 to 17 years of age
who meet International Classification of Headache Disorders (ICHD-3) criteria
for a diagnosis of migraine with episodic frequency as confirmed during a
1-month prospective baseline period.

Sites will administer subcutaneous injections of galcanezumab or placebo at 3
clinic visits during the double-blind treatment phase and administer
galcanezumab at 9 clinic visits during the open-label treatment phase, SP IV
(Section 2). The injection may be given in the abdomen, thigh, upper arm or
buttocks. Site staff may administer comfort measures (such as topical
anesthetic cream, cold compress, or ice pack) to the injection site prior to or
after the injection at their clinical discretion or as needed. Use of
distraction devices during the injection are also
acceptable.
Based on these pediatric dose regimens, the lighter patients (15 to 45 kg)
compared with heavier patients (>45 kg) will receive 1 fewer injection and 50%
of the total volume at Visit 3, and 50% less volume at Visits 5, 6, and 8 to 15.

See Protocol page 37 and 38, Table 7.1 and Section 7.1.1 for additional details

Interim analysis of the ongoing pharmacokinetic (PK) addendum to Study CGAS (n
= 25, 21 weighing at least 30 kg and 4 patients weighing less than 30 kg) in
which pediatric patients received at least 1 subcutaneous injection with 120 mg
galcanezumab (1 mL) indicated no
reatment-related SAEs and no discontinuations due to adverse reactions. Most
of the AEs of all causality were mild to moderate in severity. All AEs
considered to be related to study drug dosing were mild to moderate in
severity, and all but one event had resolved. There were no trends of higher AE
risk in patients with longer galcanezumab exposure or lower body weight. Vital
signs, safety laboratory tests, and electrocardiogram (ECG) findings were not
clinically significant.

Given the above safety profile and the need of treatment for children and
adolescents with migraine it is supported to evaluate the use galcanezumab in
pediatric population,