Clinical trial NCT05757141: An Open-Label Exploratory Study of Fosigotifator in Participants With Vanishing White Matter Disease
Official title: A Phase 1b/2 Open-label Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Exploratory Efficacy Following Fosigotifator Administration in Adult and Pediatric Subjects With Vanishing White Matter Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Vanishing White Matter Disease
Keywords: Neurodegenerative Diseases
Nervous System Diseases
Central Nervous System Brain Diseases
Hereditary Central Nervous System
Leukoencephalopathy with Vanishing White Matter
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Calico Life Sciences LLC
First posted: 2023-03-07
Enrollment: 50
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Fosigotifator is an investigational drug being researched for the treatment of Vanishing White Matter disease in adult, pediatric and infant participants. This is a 201-week, open-label, multiple cohort study enrolling adults, pediatric and infant participants with Vanishing White Matter disease.

Participants will attend regular visits during the course of the study and complete medical assessments, blood tests, questionnaires, and be evaluated for side effects.


Eligibility criteria: Inclusion Criteria:

1. Males and females \>= 6 months of age at the time of Screening.
2. Have VWM disease defined as:

   1. A clinical diagnosis by a physician experienced in the assessment of VWM disease; and
   2. A molecular diagnosis of VWM disease, and
   3. A magnetic resonance imaging (MRI) presentation consistent with VWM disease.
3. Have a designated caregiver who is able to complete the respective caregiver-centered assessments.
4. Signed and dated informed consent provided by the participant, or from a legally authorized representative (LAR) if participant is incapable to consent themselves.
5. Participants must meet criteria (a) and at least one of the following functional criteria (b or c):

   1. Medical history of at least 1 neurological symptom that is assessed by the investigator as having a reasonable possibility of being related to VWM disease.
   2. Motor criteria defined as inability to walk 10 or more steps with or without light support of 2 hands
   3. Cognitive criteria as assessed by the age-appropriate version of the Wechsler Intelligence Scale, with participants scoring \< 50 on specific indices; specific details can be provided by the Study physician.
6. Pediatric participants in Cohort 4 must meet both criteria a and b below, or criterion c:

   1. Medical history of at least 1 neurological symptom that is assessed by the investigator as having a reasonable possibility of being related to VWM disease.
   2. Motor criteria as defined below:

   i. More than minimal head control as demonstrated by: While in prone position, the participant can lift his/her head and sustain the position for 10 seconds and bring his/her arms actively to weight bearing in that position.

   c. Presymptomatic and homozygous for Cree Leukoencephalopathy (EIF2B5 R195H) or other mutation with known imminent risk of significant clinical decline or death (sponsor must be notified and provide approval prior to screening and enrolling a participant that meets eligibility with only this criterion).
7. All male participants who are sexually active and not surgically sterilized must agree to use an acceptable contraceptive method. Additionally, male participants must agree to not donate sperm during the study until 30 days after the final dose of study drug.
8. All female participants who are sexually active and of childbearing potential must agree to use a highly effective contraceptive method. Additionally, female participants must agree to not donate eggs during the study and for 30 days after the final dose of study drug.

Exclusion Criteria:

1. Pediatric participants \>= 6 months and \< 6 years of age must not be on any form of respiratory support at the time of Screening.
2. Changes in medication use for the management of VWM disease symptoms within the 4 weeks preceding Screening.
3. Seizure disorder not considered adequately controlled by the investigator within the 6 months preceding Screening.
4. Participant who, in the opinion of the investigator, is incapable of completing study-required visits and procedures to assess primary and secondary endpoints.
5. Adult female participants who are pregnant, breastfeeding or providing breast milk.
6. Treatment with any other investigational treatment within 30 days or 5 half-lives (whichever is longer) prior to Baseline.
7. Any clinically significant laboratory or imaging findings at Screening.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Baseline up to Approximately Day 28
measure: Number of Participants with Change in Vital Signs
timeFrame: Baseline up to Approximately Day 28
measure: Number of Participants with Change in ECG
timeFrame: Baseline up to Approximately Day 28
measure: Number of Participants with Change in Clinical Laboratory Tests
timeFrame: Baseline up to Approximately Day 28
measure: Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline up to Approximately Day 28
measure: Plasma Concentration of Fosigotifator
timeFrame: Baseline up to approximately Week 96
measure: Time to Cmax (Tmax) of Fosigotifator
timeFrame: Baseline up to approximately Week 96
measure: Area Under the Plasma Concentration-Time Curve (AUC0-24h) of Fosigotifator
timeFrame: Baseline up to approximately Week 96
measure: Trough Concentration (Ctrough) of Fosigotifator
timeFrame: Baseline up to approximately Week 96
measure: Terminal Elimination Half-Life (t1/2) of Fosigotifator
timeFrame: Baseline up to approximately Week 96
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Baseline up to Approximately Week 197
measure: Number of Participants with Change in Vital Signs
timeFrame: Baseline up to approximately Week 197
measure: Number of Participants with Change in ECG
timeFrame: Baseline up to approximately Week 197
measure: Number of Participants with Change in Clinical Laboratory Tests
timeFrame: Baseline up to approximately Week 197
measure: Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline up to approximately Week 197
measure: Number of Participants with Change in Magnetic Resonance Imaging (MRI)
timeFrame: Baseline up to approximately Week 192
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital /ID# 270960
state: Massachusetts
city: Salt Lake City
country: United States
facility: University of Utah /ID# 255624
state: Utah
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, locatie VUmc /ID# 270955
state: Noord-Holland
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: