AMG 334 20160172 Pediatric Migraine PK Study.

A Phase I, Randomized, Open-label, Multiple-dose Study to Evaluate Safety, Tolerability, and Pharmacokinetics of AMG 334 in Children and Adolescents With Migraine

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03499119

Enrollment

Registered

2018-04-17

Start date

2018-05-04

Completion date

2021-11-23

Last updated

2024-05-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Migraine

Brief summary

AMG 334 20160172 Pediatric Migraine PK Study.

Detailed description

An Open-label, Randomized, Multiple-dose Study to Evaluate Safety, Tolerability, and Pharmacokinetics of AMG 334 in Children and Adolescents With Migraine

Interventions

DRUGAMG 334 Dose 1

Subjects weighing less than weight threshold at Day 1 will be randomized to either Dose 1 or Dose 3. Subjects weighing weight threshold or more at Day 1 will be randomized to either Dose 1 or Dose 2

DRUGAMG 334 Dose 2

Subjects weighing weight threshold or more at Day 1 will be randomized to either Dose 1 or Dose 2.

DRUGAMG 334 Dose 3

Subjects weighing less than weight threshold at Day 1 will be randomized to either Dose 1 or Dose 3.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

6 Years to 17 Years

Healthy volunteers

Inclusion criteria

* Subject's legally acceptable representative has provided informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated. * Male and female children and adolescents ≥ 6 and \<18 years of age upon entry into screening * Diagnosis of migraines, with or without aura, according to the International Classification of Headache Disorders (ICHD 3rd Edition, 2013) for at least 12 months prior to the study screening * Frequency of migraine of ≥ 4 migraine days per month in each of the 3 months prior to the study screening period

Exclusion criteria

* Currently receiving treatment in another investigational device or drug study * History of migraine with brainstem aura or hemiplegic migraine headache * Medical history or other condition that compromises the ability of the subject or legally acceptable representative to give appropriate informed consent and/or assent * Malignancy except non-melanoma skin cancers or cervical cancer in situ within the last 5 years. * Presence of any clinical condition that in opinion of the investigator might increased the risk of subjects participating in the study.

Design outcomes

Primary

Measure	Time frame	Description
Time to Maximum Concentration (Tmax) of Erenumab	First dose: Days 1 (pre-dose), 8, 15, and 29 (pre-dose); third dose: Days 57 (pre-dose), 64, 71, and 85	Blood samples for pharmacokinetic (PK) testing were collected for the measurement of PK concentrations. Serum erenumab concentrations were determined using a validated assay. Noncompartmental analysis (NCA) was performed for erenumab PK parameter estimation.
Maximum Observed Concentration (Cmax) of Erenumab	First dose: Days 1 (pre-dose), 8, 15, and 29 (pre-dose); third dose: Days 57 (pre-dose), 64, 71, and 85	Blood samples for PK testing were collected for the measurement of PK concentrations. Serum erenumab concentrations were determined using a validated assay. NCA was performed for erenumab PK parameter estimation.
Trough Concentration (Ctrough) of Erenumab	First dose: Days 1 (pre-dose), 8, 15, and 29 (pre-dose); third dose: Days 57 (pre-dose), 64, 71, and 85	Blood samples for PK testing were collected for the measurement of PK concentrations. Serum erenumab concentrations were determined using a validated assay. NCA was performed for erenumab PK parameter estimation.
Area Under the Concentration Time Curve From 0 to 28 Days (AUC0-28day) of Erenumab	First dose: Days 1 (pre-dose), 8, 15, and 29 (pre-dose); third dose: Days 57 (pre-dose), 64, 71, and 85	Blood samples for PK testing were collected for the measurement of PK concentrations. Serum erenumab concentrations were determined using a validated assay. NCA was performed for erenumab PK parameter estimation.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Up to Week 52 + 16-week safety follow-up	An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant. A TEAE was defined as an AE starting on or after first dose of investigational product. The event did not necessarily have a causal relationship with study treatment.
Number of Participants With Clinically Significant Changes in Vital Signs Measurements	Up to Week 52 + 16-week safety follow-up	The following measurements were performed: systolic/diastolic blood pressure, heart rate, and temperature.
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Measurements	Up to Week 52	Clinically significant changes in ECG was defined as incidence of abnormal ECG diagnosis based on 12-lead ECG including heart rate, QRS, QTc and PR intervals.
Number of Participants With Clinically Significant Changes in Clinical Laboratory Safety Tests	Up to Week 52 + 16-week safety follow-up	The clinical laboratory safety tests included: chemistry, hematology, and urinalysis.
Number of Participants With Clinically Significant Changes in Neurological Assessments	Up to Week 52 + 16-week safety follow-up	The neurological examinations were completed as per standard of care.

Countries

United States

Participant flow

Recruitment details

Of the 63 participants screened, 53 participants were enrolled at 9 centers in the United States between 04 May 2018 and 23 November 2021. Enrollment was staggered by age category with adolescents 12 to \< 18 years of age starting enrollment first, followed by children 6 to \< 12 years of age.

Pre-assignment details

Participants weighing \< 40 kg (Cohort 1) received a dose of either 35 mg or 70 mg erenumab. Participants weighing ≥ 40 kg (Cohort 2) received a dose of either 70 mg or 140 mg erenumab. All participants participated in the initial treatment phase for a total of 12 weeks of treatment. Adolescents 12 to \< 18 years of age at time of consent had the option of continuing treatment with the same dose they received in the initial treatment phase in a 40-week extension phase.

Participants by arm

Arm	Count
Cohort 1: Erenumab 35 mg Participants weighing \< 40 kg received a dose of 35 mg erenumab Q4W via SC injection in the initial 12-week treatment phase. Adolescents 12 to \< 18 years of age at time of consent had the option of continuing treatment with the same dose they received in the initial treatment phase in a 40-week extension phase, for a total of 52 weeks of treatment.	4
Cohort 1: Erenumab 70 mg Participants weighing \< 40 kg received a dose of 70 mg erenumab Q4W via SC injection in the initial 12-week treatment phase. Adolescents 12 to \< 18 years of age at time of consent had the option of continuing treatment with the same dose they received in the initial treatment phase in a 40-week extension phase, for a total of 52 weeks of treatment.	9
Cohort 2: Erenumab 70 mg Participants weighing ≥ 40 kg received a dose of 70 mg erenumab Q4W via SC injection in the initial 12-week treatment phase. Adolescents 12 to \< 18 years of age at time of consent had the option of continuing treatment with the same dose they received in the initial treatment phase in a 40-week extension phase, for a total of 52 weeks of treatment.	8
Cohort 2: Erenumab 140 mg Participants weighing ≥ 40 kg received a dose of 140 mg erenumab Q4W via SC injection in the initial 12-week treatment phase. Adolescents 12 to \< 18 years of age at time of consent had the option of continuing treatment with the same dose they received in the initial treatment phase in a 40-week extension phase, for a total of 52 weeks of treatment.	32
Total	53

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Initial Treatment Phase	Decision by Sponsor	1	0	1	1
Initial Treatment Phase	Protocol Specified Criteria	0	0	0	1
Initial Treatment Phase	Withdrawal by Subject	0	0	0	1
Optional Extension Phase	Lost to Follow-up	0	0	0	1
Optional Extension Phase	Protocol Specified Criteria	0	1	0	0
Optional Extension Phase	Withdrawal by Subject	0	0	0	5

Baseline characteristics

Characteristic	Cohort 1: Erenumab 35 mg	Cohort 1: Erenumab 70 mg	Cohort 2: Erenumab 70 mg	Cohort 2: Erenumab 140 mg	Total
Age, Continuous	10.8 years STANDARD_DEVIATION 1.7	10.4 years STANDARD_DEVIATION 1	14.6 years STANDARD_DEVIATION 1.3	15.4 years STANDARD_DEVIATION 1.5	14.1 years STANDARD_DEVIATION 2.5
Age, Customized Adolescents (12 to < 18 years)	1 Participants	2 Participants	8 Participants	32 Participants	43 Participants
Age, Customized Children (6 to < 12 years)	3 Participants	7 Participants	0 Participants	0 Participants	10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	1 Participants	0 Participants	2 Participants	4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants	8 Participants	8 Participants	30 Participants	49 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Black (or African American)	0 Participants	2 Participants	1 Participants	4 Participants	7 Participants
Race/Ethnicity, Customized Multiple	0 Participants	0 Participants	0 Participants	2 Participants	2 Participants
Race/Ethnicity, Customized Other	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized White	4 Participants	6 Participants	7 Participants	26 Participants	43 Participants
Sex: Female, Male Female	1 Participants	3 Participants	4 Participants	23 Participants	31 Participants
Sex: Female, Male Male	3 Participants	6 Participants	4 Participants	9 Participants	22 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk
deaths Total, all-cause mortality	0 / 4	0 / 9	0 / 8	0 / 32	0 / 1	0 / 3	0 / 5	0 / 27
other Total, other adverse events	2 / 4	6 / 9	6 / 8	19 / 32	0 / 1	2 / 3	4 / 5	19 / 27
serious Total, serious adverse events	0 / 4	0 / 9	1 / 8	1 / 32	0 / 1	1 / 3	0 / 5	1 / 27

Outcome results

Primary

Area Under the Concentration Time Curve From 0 to 28 Days (AUC0-28day) of Erenumab

Blood samples for PK testing were collected for the measurement of PK concentrations. Serum erenumab concentrations were determined using a validated assay. NCA was performed for erenumab PK parameter estimation.

Time frame: First dose: Days 1 (pre-dose), 8, 15, and 29 (pre-dose); third dose: Days 57 (pre-dose), 64, 71, and 85

Population: The PK analysis set contained all randomized participants who received at least 1 dose of erenumab and had at least 1 PK concentration result. Data were excluded from the NCA if:~* participants missed the previous dose or the actual time deviated by \> 30% from the nominal sample collection time~* PK profile was missing \> 2 samples~* PK values at the beginning or end of PK profile were missing, or~* predose PK sample concentration was \> 5% of maximum concentration value.

Arm	Measure	Group	Value (MEDIAN)
Cohort 1: Erenumab 35 mg	Area Under the Concentration Time Curve From 0 to 28 Days (AUC0-28day) of Erenumab	First Dose	175 day*μg/mL
Cohort 1: Erenumab 35 mg	Area Under the Concentration Time Curve From 0 to 28 Days (AUC0-28day) of Erenumab	Third Dose	243 day*μg/mL
Cohort 1: Erenumab 70 mg	Area Under the Concentration Time Curve From 0 to 28 Days (AUC0-28day) of Erenumab	Third Dose	465 day*μg/mL
Cohort 1: Erenumab 70 mg	Area Under the Concentration Time Curve From 0 to 28 Days (AUC0-28day) of Erenumab	First Dose	282 day*μg/mL
Cohort 2: Erenumab 70 mg	Area Under the Concentration Time Curve From 0 to 28 Days (AUC0-28day) of Erenumab	First Dose	151 day*μg/mL
Cohort 2: Erenumab 70 mg	Area Under the Concentration Time Curve From 0 to 28 Days (AUC0-28day) of Erenumab	Third Dose	329 day*μg/mL
Cohort 2: Erenumab 140 mg	Area Under the Concentration Time Curve From 0 to 28 Days (AUC0-28day) of Erenumab	First Dose	277 day*μg/mL
Cohort 2: Erenumab 140 mg	Area Under the Concentration Time Curve From 0 to 28 Days (AUC0-28day) of Erenumab	Third Dose	475 day*μg/mL

Primary

Maximum Observed Concentration (Cmax) of Erenumab

Time frame: First dose: Days 1 (pre-dose), 8, 15, and 29 (pre-dose); third dose: Days 57 (pre-dose), 64, 71, and 85

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1: Erenumab 35 mg	Maximum Observed Concentration (Cmax) of Erenumab	First Dose	7.92 μg/mL	Standard Deviation 0.947
Cohort 1: Erenumab 35 mg	Maximum Observed Concentration (Cmax) of Erenumab	Third Dose	11.3 μg/mL	Standard Deviation 3.14
Cohort 1: Erenumab 70 mg	Maximum Observed Concentration (Cmax) of Erenumab	Third Dose	18.9 μg/mL	Standard Deviation 7.29
Cohort 1: Erenumab 70 mg	Maximum Observed Concentration (Cmax) of Erenumab	First Dose	13.3 μg/mL	Standard Deviation 4.85
Cohort 2: Erenumab 70 mg	Maximum Observed Concentration (Cmax) of Erenumab	First Dose	7.16 μg/mL	Standard Deviation 1.76
Cohort 2: Erenumab 70 mg	Maximum Observed Concentration (Cmax) of Erenumab	Third Dose	14.1 μg/mL	Standard Deviation 5.54
Cohort 2: Erenumab 140 mg	Maximum Observed Concentration (Cmax) of Erenumab	First Dose	13.4 μg/mL	Standard Deviation 4.53
Cohort 2: Erenumab 140 mg	Maximum Observed Concentration (Cmax) of Erenumab	Third Dose	23.7 μg/mL	Standard Deviation 8.83

Primary