An Open-Label Exploratory Study of Fosigotifator in Participants With Vanishing White Matter Disease

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

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.

Study Overview

• Status: Recruiting
• Conditions: Vanishing White Matter Disease
• Intervention / Treatment: Drug: Fosigotifator

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Call Center - English; Phone Number: 1-833-250-9660; Email: vwminfo@mylocalstudy.com

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3H2L9
      • Recruiting
      • McGill University Health Centre - Glen Site
• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1081 HV
      • Recruiting
      • Amsterdam UMC, locatie VUmc /ID# 270955
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital /ID# 270960
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
  • Utah
    • Salt Lake City, Utah, United States, 84112-5339
      • Recruiting
      • University of Utah /ID# 255624

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fosigotifator - Cohort 1; Cohort 1: VWM adults >= 18 years.	Drug: Fosigotifator; Oral Use; Other Names: ABBV-CLS-7262
Experimental: Fosigotifator - Cohort 1b; Cohort 1b: VWM adults >= 18 years.	Drug: Fosigotifator; Oral Use; Other Names: ABBV-CLS-7262
Experimental: Fosigotifator - Cohort 2; Cohort 2: VWM children>= 12 y and <18 years.	Drug: Fosigotifator; Oral Use; Other Names: ABBV-CLS-7262
Experimental: Fosigotifator - Cohort 3; Cohort 3: VWM children >= 6 y and <12 years.	Drug: Fosigotifator; Oral Use; Other Names: ABBV-CLS-7262
Experimental: Fosigotifator - Cohort 4; Cohort 4: VWM children >= 6 months and <6 years.	Drug: Fosigotifator; Oral Use; Other Names: ABBV-CLS-7262

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentration of Fosigotifator	Maximum Plasma Concentration [Cmax]	Baseline up to approximately Week 96
Incidence of Treatment-Emergent Adverse Events	Number of participants with treatment-related adverse events as assessed by CTCAE v4.03	Baseline up to Approximately Day 28
Number of Participants with Change in Vital Signs	Number of Participants with Change in Vital Signs will be assessed.	Baseline up to Approximately Day 28
Number of Participants with Change in ECG	Number of Participants with Change in ECG will be assessed.	Baseline up to Approximately Day 28
Number of Participants with Change in Clinical Laboratory Tests	Number of participants with change in clinical laboratory tests will be assessed.	Baseline up to Approximately Day 28
Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)	The C-SSRS is a systematically administered instrument that reports the severity of both suicidal ideation and behavior, with a higher score denoting more severe suicidal ideation and behavior.	Baseline up to Approximately Day 28
Time to Cmax (Tmax) of Fosigotifator	Tmax of Fosigotifator	Baseline up to approximately Week 96
Area Under the Plasma Concentration-Time Curve (AUC0-24h) of Fosigotifator	AUC0-24h of Fosigotifator	Baseline up to approximately Week 96
Trough Concentration (Ctrough) of Fosigotifator	Ctrough of Fosigotifator	Baseline up to approximately Week 96
Terminal Elimination Half-Life (t1/2) of Fosigotifator	t1/2 of Fosigotifator	Baseline up to approximately Week 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Number of patients with treatment-related adverse events as assessed by CTCAE v4.03	Baseline up to Approximately Week 197
Number of Participants with Change in Vital Signs	Number of Participants with Change in Vital Signs will be assessed.	Baseline up to approximately Week 197
Number of Participants with Change in ECG	Number of Participants with Change in ECG will be assessed.	Baseline up to approximately Week 197
Number of Participants with Change in Clinical Laboratory Tests	Number of participants with change in clinical laboratory tests will be assessed.	Baseline up to approximately Week 197
Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)	The C-SSRS is a systematically administered instrument that reports the severity of both suicidal ideation and behavior, with a higher score denoting more severe suicidal ideation and behavior.	Baseline up to approximately Week 197
Number of Participants with Change in Magnetic Resonance Imaging (MRI)	Change in Brain Magnetic Resonance Imaging (MRI) associated with adverse events.	Baseline up to approximately Week 192

Collaborators and Investigators

• Sponsor: Calico Life Sciences LLC
• Collaborators: Calico Life Sciences LLC
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2023
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2029

Study Registration Dates

• First Submitted: February 23, 2023
• First Submitted That Met QC Criteria: March 3, 2023
• First Posted (Actual): March 7, 2023

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Nervous System Diseases; Neurodegenerative Diseases; Central Nervous System Brain Diseases; Hereditary Central Nervous System; Leukoencephalopathy with Vanishing White Matter
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Leukoencephalopathies
• Other Study ID Numbers: M23-523; 2023-505704-30-00 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.
• IPD Sharing Time Frame: For details on when studies are available for sharing, visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes