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

Phase 1

Recruiting

• Conditions: Vanishing White Matter Disease
• Interventions: Drug: Fosigotifator

• Registration Number: NCT05757141
• Lead Sponsor: Calico Life Sciences LLC

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-02-23
• Study First Submitted QC: 2023-03-03
• Study First Posted: 2023-03-07
• Study Start: 2023-03-13
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-24
• Last Update Posted: 2025-09-29
• Primary Completion: 2027-11
• Study Completion: 2029-11-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fosigotifator - Cohort 1	Fosigotifator	Cohort 1: VWM adults \>= 18 years.
Fosigotifator - Cohort 1b	Fosigotifator	Cohort 1b: VWM adults \>= 18 years.
Fosigotifator - Cohort 2	Fosigotifator	Cohort 2: VWM children\>= 12 y and \<18 years.
Fosigotifator - Cohort 3	Fosigotifator	Cohort 3: VWM children \>= 6 y and \<12 years.
Fosigotifator - Cohort 4	Fosigotifator	Cohort 4: VWM children \>= 6 months and \<6 years.

Primary Outcome Measures

Name	Time	Method
Number of Participants with Change in Vital Signs	Baseline up to Approximately Day 28	Number of Participants with Change in Vital Signs will be assessed.
Number of Participants with Change in ECG	Baseline up to Approximately Day 28	Number of Participants with Change in ECG will be assessed.
Number of Participants with Change in Clinical Laboratory Tests	Baseline up to Approximately Day 28	Number of participants with change in clinical laboratory tests will be assessed.
Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)	Baseline up to Approximately Day 28	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.
Plasma Concentration of Fosigotifator	Baseline up to approximately Week 96	Maximum Plasma Concentration \[Cmax\]
Time to Cmax (Tmax) of Fosigotifator	Baseline up to approximately Week 96	Tmax of Fosigotifator
Area Under the Plasma Concentration-Time Curve (AUC0-24h) of Fosigotifator	Baseline up to approximately Week 96	AUC0-24h of Fosigotifator
Trough Concentration (Ctrough) of Fosigotifator	Baseline up to approximately Week 96	Ctrough of Fosigotifator
Terminal Elimination Half-Life (t1/2) of Fosigotifator	Baseline up to approximately Week 96	t1/2 of Fosigotifator
Incidence of Treatment-Emergent Adverse Events	Baseline up to Approximately Day 28	Number of participants with treatment-related adverse events as assessed by CTCAE v4.03

Secondary Outcome Measures

Name	Time	Method
Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)	Baseline up to approximately Week 197	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.
Number of Participants with Change in Magnetic Resonance Imaging (MRI)	Baseline up to approximately Week 192	Change in Brain Magnetic Resonance Imaging (MRI) associated with adverse events.
Incidence of Treatment-Emergent Adverse Events	Baseline up to Approximately Week 197	Number of patients with treatment-related adverse events as assessed by CTCAE v4.03
Number of Participants with Change in Vital Signs	Baseline up to approximately Week 197	Number of Participants with Change in Vital Signs will be assessed.
Number of Participants with Change in ECG	Baseline up to approximately Week 197	Number of Participants with Change in ECG will be assessed.
Number of Participants with Change in Clinical Laboratory Tests	Baseline up to approximately Week 197	Number of participants with change in clinical laboratory tests will be assessed.

Trial Locations

Locations (5)

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

McGill University Health Centre - Glen Site; 🇨🇦 Montreal, Quebec, Canada

Massachusetts General Hospital /ID# 270960; 🇺🇸 Boston, Massachusetts, United States

University of Utah /ID# 255624; 🇺🇸 Salt Lake City, Utah, United States

Amsterdam UMC, locatie VUmc /ID# 270955; 🇳🇱 Amsterdam, North Holland, Netherlands