This study has been transitioned to CTIS with ID 2024-512837-34-00 check the CTIS register for the current data. Main objective:To evaluate the long-term safety and tolerability of subcutaneous test IMP in the preventive treatment of migraine in…
ID
Source
Brief title
Condition
- Headaches
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety:
-Occurrence of adverse events throughout the trial, including local
injection site reactions/pain
-Changes from baseline in clinical laboratory (serum chemistry,
hematology, coagulation, and urinalysis) test results and height and
weight measurements taken at V5, V8, and at the end of treatment
(V11)
-Abnormal standard 12-lead electrocardiogram findings at each trial visit
up to the end of treatment (V11)
-Changes from baseline in vital signs (pulse, systolic and diastolic blood
pressure, temperature, and respiratory rate) at each trial visit up to the
end of treatment (V11)
-Abnormal physical examination findings at trial visits V6, V7, V11, and
V12
-Suicidal ideation and behavior as suggested by the Columbia-Suicide
Severity Rating Scale throughout the trial
Secondary outcome
Efficacy:
-Mean change from baseline (defined as the original baseline from the
EM and CM studies) in the number of headache days of at least moderate
severity during the 4-week periods after V2, V6, and V10
-Mean change from baseline (defined as the original baseline from the
EM and CM studies) in the number of migraine days during the 4-week
periods after V2, V6, and V10
-Proportion of participants reaching at least 50% reduction in the
number of migraine days during the 4-week periods after V2, V6, and
V10
-Proportion of participants reaching at least 50% reduction in the number of
headache days of at least moderate severity during the 4week periods after V2,
V6, and V10
-Mean change from baseline (defined as the original baseline from the
EM and CM studies) in the number of days of use of any acute headache
medications during the 4-week periods after V2, V6, and V10
-Mean change from baseline (day 1) in migraine-related disability score,
as measured by the PedMIDAS questionnaire at V5, V8, V11, and V12
-Proportion of participants developing ADAs throughout the trial. The
impact of ADAs on safety and efficacy will be analyzed if the number of
ADA-positive participants allows
Background summary
Fremanezumab is a humanized immunoglobulin G2 (IgG2) Δa/kappa monoclonal
antibody (mAb) derived from a murine precursor. Fremanezumab is a potent,
selective calcitonin gene related peptide (CGRP) binder and blocks both CGRP
isoforms (α- and β- CGRP) from binding to the CGRP receptor. While the precise
mechanism of action by which fremanezumab prevents migraine is unknown, it is
believed that blocking CGRP prevents activation of the trigeminal system.
Fremanezumab is highly specific for CGRP and does not bind to closely related
family members (eg, amylin, calcitonin, intermedin, and adrenomedullin).
The safety and tolerability of fremanezumab (intravenous [iv] doses of 0.2 to
2000 mg and subcutaneous [sc] doses of 225 to 900 mg) as well as the
pharmacokinetic profile of 225 to 900 mg sc and iv have been well characterized
in the Phase 1 development program in adults.
Furthermore, the safety and effectiveness of fremanezumab have been
demonstrated in 2 Phase 2b studies and 3 Phase 3 studies in adult patients with
migraine.
The pediatric migraine development program includes a completed Phase 1,
single-dose, open-label study with administration of single sc doses of 75 mg
in pediatric migraine patients 6 to 11 years of age, inclusive (Study
TV48125-CNS-10141).
Migraine is a prevalent condition characterized by attacks of headache and
associated symptoms (such as nausea, photophobia, or phonophobia).
Migraine has been classified by headache frequency in the International
Classification of Headache Disorders (ICHD) and is described as EM, which is
defined as headaches occurring on less than 15 days per month, and CM, which is
defined as headaches on at least 15 days per month for at least 3 months, with
the features of migraine on at least 8 days per month (Headache Classification
Committee of the IHS 2013, Lipton and Silberstein 2015).
Treatment options for migraine include non-pharmacological biobehavioral
strategies and pharmacological strategies. Topiramate is the only migraine
preventive medication approved for pediatric populations, but it is not
approved in all regions of the EU and is limited to adolescents ages 12 through
17.
Overall, authorized medications for the acute and prophylactic treatment of
migraine in children and medications that are being used off-label in children
have limited evidence to support their use, require ongoing patient monitoring,
or are associated with undesirable or intolerable adverse effects (Barnes 2015,
Kacperski 2015). Therefore, there is an unmet medical need for a safe and
effective prophylactic treatment for EM and CM in the pediatric population.
The purpose of the study is to determine the long-term safety of fremanezumab.
Study objective
This study has been transitioned to CTIS with ID 2024-512837-34-00 check the CTIS register for the current data.
Main objective:
To evaluate the long-term safety and tolerability of subcutaneous test IMP in
the preventive treatment of migraine in pediatric participants 6 to 17 years of
age (inclusive at enrollment in the pivotal trial)
Secondary objectives:
-To evaluate the efficacy of subcutaneous test IMP in pediatric participants
with migraine
-To evaluate the immunogenicity of test IMP and the impact of ADAs on clinical
outcomes in pediatric participants exposed to test IMP
Study design
This is a multicenter, open-label study evaluating the long-term safety,
tolerability, and efficacy of monthly sc administrations of fremanezumab for
the preventive treatment of migraine (EM and CM) in male and female pediatric
patients 6 to 17 years of age (inclusive at enrollment in the pivotal study).
Patients rolling over from the pharmacokinetic study (Study TV48125-CNS-10141)
will begin this study at visit 1 (screening); those who are eligible will
complete a 28-day baseline period before returning to the study for the first
dosing at visit 2. Patients rolling over from the pivotal studies (Studies
TV48125 CNS 30082 and TV48125-CNS-30083) will begin the study at visit 2.
Open-label treatment will be administered sc monthly (every 28 days) for a
total of 9 doses, after which the patients will be followed for 6 months from
the last study drug administration for the collection of pharmacokinetic,
immunogenicity samples, efficacy, and safety assessments.
Intervention
For patients who enter this study, the monthly dose of fremanezumab to be
administered will be confirmed or adjusted, as appropriate, based on the
patient*s weight every 3 months. Patients weighing >=45.0 kg on the day of
dosing will receive a fremanezumab dose of 225 mg. Patients weighing <45.0 kg
on the day of dosing will receive fremanezumab dose of 120 mg.
For this study, monthly dosing refers to dosing approximately every 4 weeks (28
days).
Study burden and risks
Identified Risks
• injection site induration
• injection site erythema
• injection site pruritus
• injection site rash
• injection site pain
None of these risks impact the risk-benefit profile.
Important Potential Risk
Severe hypersensitivity reactions are regarded as a potential risk for
fremanezumab. Mild and moderate drug hypersensitivity events were observed
infrequently and with similar incidence in placebo and fremanezumab in the
clinical development program, but no anaphylaxis or severe hypersensitivity
reactions were seen. However, it cannot be excluded that severe events may
occur in the future. For additional details, refer to the current IB, Section
*7.5.5.
Based on the available efficacy and safety data for fremanezumab, the
benefit-risk profile is favorable.
Overall Benefit and Risk Assessment for This Study
Based on the current safety profile and the demonstrated efficacy of the sc
fremanezumab dosage form as observed in adults, the overall risk and benefit
assessment for this study is favorable.
Brandywine Parkway 145
West Chester 19380
US
Brandywine Parkway 145
West Chester 19380
US
Listed location countries
Age
Inclusion criteria
Participants Rolling Over from the Pivotal Efficacy Trials may be included only
if they meet all of the following criteria:
a. Completion of the pivotal efficacy trial and in the opinion of the
Investigator/Sponsor able to complete the trial in a safe and compliant way
b. Participant's parent(s) or legal guardian(s) must give written informed
consent, and the participant must give assent (in accordance with local
regulations) Note: In some countries, participants aged 15 to 17 years
(inclusive) may give written informed consent; however, the participant's
parent(s) or legal guardian(s) must be informed, per local regulations.
c. Participant may continue with a stable dose/regimen of the preventive
medication they were taking during the pivotal efficacy trials
d. Willing and able to comply with trial restrictions and to remain at the
clinic for the required duration during the trial period and willing to
return to the clinic for the follow-up evaluation as specified in this
protocol
e. Participant continues to meet appropriate criteria carried forward
from the pivotal efficacy trial, as follows:
f. Females who are postmenarchal or >=12 years of age may be included only if
they have a negative beta-human chorionic gonadotropin (β-HCG)
test before day 1 or are sterile
g. Females who are postmenarchal or >=12 years of age and sexually
active must use highly effective birth control methods with their male
partners for the duration of the trial (ie, at least 2 months before day 1)
and for 6 months after the last dose of IMP. Males who are sexually
active with female partners must use a condom for the duration of the
trial and for 6 months after the last administration of IMP
h. Receipt of all recommended age-appropriate vaccines according to
local standard of care and schedule
i. Good health, determined by a medical and psychiatric history, medical
examination, 12-lead ECG, serum chemistry, hematology, coagulation,
urinalysis, and serology
j. Weight of at least 17.0 kg on the day of trial enrollment
k. BMI ranging from the 5th to 120% of the 95th percentile, incl. at
day1, based on the local standard
Participants Rolling Over from Trial TV48125-CNS-10141: may be
included only if they meet all of the following criteria
a. Participant is male/female, 6 - 17 years old (inclusive)
b. Written informed consent is obtained from each participant's parent or
legal guardian and written assent (according to local regulations) is
obtained from each participant. Note: In some countries, participants
aged 15 to 17 years (inclusive) may give written informed consent;
however, the participant's parent(s) or legal guardian(s) must be
informed, per local regulations. Note: In some countries, participants
aged 15 to 17 years (inclusive) may give written informed consent;
however, the participant's parent(s) or legal guardian(s) must be
informed, per local regulations
c. The participant/caregiver has demonstrated compliance with the
electronic headache diary during the 28-day baseline period by entry of
headache data on a minimum of 21 out of 28 days (approximately 75%
diary compliance)
d. Females who are postmenarchal or >=12 years of age may be included
only if they have a negative β-HCG test before day 1 or are sterile
e. Females who are postmenarchal or >=12 years of age and sexually
active must use highly effective birth control methods with their male
partners for the duration of the trial (ie, at least 2 months before day 1)
and for 6 months after the last dose of the IMP. Males who are sexually
active with female partners must use a condom for the duration of the
trial and for 6 months after the last administration of the IMP
f. The participant has received all recommended age-appropriate
vaccines according to local standard of care and schedule
g. The participant is in good health as determined by a medical and
psychiatric history, medical examination, 12-lead ECG, serum chemistry,
hematology, coagulation, urinalysis, and serology
h. The participant/caregiver must be willing and able to comply with
trial requirements and to remain at the clinic for the required duration
during the trial period, and willing to return to the clinic for the followup
evaluation
as specified in this protocol
i. Weight of at least 17.0 kg on the day of trial
enrollment
j. BMI ranging from the 5th to 120% of the 95th percentile, inclusive, at
screening, based on the local standard.
k. Not using preventive medications or using no more than 2 preventive
medications for migraine or other medical condition, as long as the dose
and regimen have been stable for at least 2 months prior to day 1
Participants Rolling Over from the Pivotal Efficacy Trials: Remainder of
criteria applies as per the trial protocol
Exclusion criteria
Participants from the Pivotal Efficacy Trials (any criteria met):
a. Significant abnormal finding on trial entry (e.g. hematology), repeat
abnormal tests for confirmation
b. Pregnant or nursing
c. Abnormal clinically significant finding on day 1 12-lead ECG
d. One of the following criteria is met:
e. Use of medications containing opioids (incl. codeine), barbiturates
(incl. Fiorinal®, any other combination containing butalbital) for
migraine treatment during the 3 months prior to screening visit day
f. Use of an intervention/device (eg, scheduled nerve block or
transcranial magnetic stimulation) for the treatment of migraine or in
the head or neck area for any condition during the 2 months prior to the
day 1
g. Any clinically significant disease (e.g. cardiovascular), or
complications of an infection
h. History of clinically significant psychiatric condition/history of a
suicide attempt/history of suicidal ideation with a specific plan within
the past 2 years, at the discretion of the investigator
i. Ongoing infection/known history of e.g. HIV infection/tuberculosis,
Lyme disease, chronic hepatitis B or C, or a known infection of
coronavirus disease 2019 (COVID-19)
j. Past or current history of cancer
k. History of hypersensitivity reactions to injected proteins, incl. mAbs,
history of Stevens-Johnson Syndrome, toxic epidermal necrolysis
syndrome, or the participant in concomitantly using lamotrigine
l. Current participation in another IMP/medical device trial
m. Hepatic enzymes (ALT, AST, ALP) > 1.5× ULN after a repeat test
confirmation, or suspected hepatocellular damage (fulfilling Hy's law)
n. Serum creatinine > 1.5× the ULN, clinically significant proteinuria
(urine dipstick +4), an estimated glomerular filtration rate (eGFR) of
<75 mL/min/1.73 m2, as calculated by the revised Schwartz formula
(eGFR=[0.413×Ht]/serum creatinine), or evidence of renal disease
o. Participant cannot fully participate in/successfully complete the trial
for its full duration for any of the following reasons:
-In custody due to an administrative or a legal decision or in residential
treatment
-Participant/caregiver unable to be contacted in case of emergency
-Presence of any other condition, which makes the participant
inappropriate for trial inclusion
-Participant is a relative of a trial center or sponsor employee who is
directly involved in the trial
p. Vulnerable participants (eg, people in detention) that are vulnerable
due to other conditions than age
q. Receipt of a live attenuated vaccine (eg, intranasal flu vaccine) within
the 12-week period prior to day 1. Note: If a medical need arises during
the trial, the participant may receive a live attenuated vaccine.
r. The participant has a known hypersensitivity to the active substance
or to any of the excipients of the trial drug.
s. The participant has a current or past medical history of hemiplegic
migraine.
Participants from Trial TV48125-CNS-10141 (any criteria met):
a. Use of an intervention/device for the treatment of migraine or in the
head or neck area for any condition during the 2 months prior to day 1.
b. Any clinically significant disease (e.g. cardiovascular)/complications
of an infection
c. Current history of clinically significant psychiatric condition/history of
a suicide attempt/suicidal ideation with a specific plan within the past 2
years, at discretion of investigator
d. Ongoing infection/known history of e.g. HIV
infection/tuberculosis/Lyme disease/chronic hepatitis B or C, COVID-19
e. Past or current history of cancer
f. Pregnant or nursing
g. History of hypersensitivity reactions to injected proteins, incl.
mAbs/history of Stevens-Johnson Syndrome/toxic epidermal necrolysis
syndrome, or participant is concomitantly using lamotrigine
h. Participation in another trial of an IMP/medical device within 30
days/ 90 days for biologics or 5 half-lives previous to screening visit day
(whichever is longer) or current participation in another trial of an
IMP/medical device
i. Exposure to a mAb targeting the calcitonin gene-related peptide
pathway (erenumab, eptinezumab, galcanezumab, fremanezumab)
during the 6 months prior to screening visit day
j. Abnormal finding on day 1 12-lead ECG considered clinically significant
k. Clinically significant abnormal finding on screening visit day, incl.
hematology, blood chemistry, coagulation tests, urinalysis
values/findings (repeat abnormal tests for confirmation)
l. Hepatic enzymes (ALT, AST, ALP) > 1.5× the ULN on screening visit
day after confirmation in a repeat test/suspected hepatocellular damage
(fulfilling Hy's law)
m. Serum creatinine > 1.5× the ULN, clinically significant proteinuria
(urine dipstick +4), an estimated glomerular filtration rate (eGFR) of
<75 mL/min/1.73 m2, as calculated by the revised Schwartz formula
(eGFR=[0.413×Ht]/serum creatinine), or evidence of renal disease on
the day of the screening visit.
Remainder of criteria applies as per the trial protocol
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-512837-34-00 |
| EudraCT | EUCTR2019-002056-16-NL |
| ClinicalTrials.gov | NCT04530110 |
| CCMO | NL74048.056.20 |