Recruiting
Phase 1
Phase 2

Fosigotifator

Sponsor:

Calico Life Sciences LLC

Code:

NCT05757141

Conditions

Vanishing White Matter Disease

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Interventions

Fosigotifator

Study Details

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.

Conditions

Vanishing White Matter Disease

Study ID

NCT05757141

Start date

Mar 13, 2023

Status verified date

Jun, 2026

Completion date

Oct, 2035

Anticipated

Primary completion date

Nov, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

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

Enrollment

50 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Fosigotifator - Cohort 1

Cohort 1: VWM adults >= 18 years.

experimental: Fosigotifator - Cohort 1b

Cohort 1b: VWM adults >= 18 years.

experimental: Fosigotifator - Cohort 2

Cohort 2: VWM children>= 12 y and <18 years.

experimental: Fosigotifator - Cohort 3

Cohort 3: VWM children >= 6 y and <12 years.

experimental: Fosigotifator - Cohort 4

Cohort 4: VWM children >= 6 months and <6 years.

Interventions

Fosigotifator

Oral Use

Primary outcome measure

  • Incidence of Treatment-Emergent Adverse Events [ Time Frame: Baseline up to Approximately Day 28 ]
  • Number of Participants with Change in Vital Signs [ Time Frame: Baseline up to Approximately Day 28 ]
  • Number of Participants with Change in ECG [ Time Frame: Baseline up to Approximately Day 28 ]
  • Number of Participants with Change in Clinical Laboratory Tests [ Time Frame: Baseline up to Approximately Day 28 ]
  • Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline up to Approximately Day 28 ]
  • Plasma Concentration of Fosigotifator [ Time Frame: Baseline up to approximately Week 96 ]
  • Time to Cmax (Tmax) of Fosigotifator [ Time Frame: Baseline up to approximately Week 96 ]
  • Area Under the Plasma Concentration-Time Curve (AUC0-24h) of Fosigotifator [ Time Frame: Baseline up to approximately Week 96 ]
  • Trough Concentration (Ctrough) of Fosigotifator [ Time Frame: Baseline up to approximately Week 96 ]
  • Terminal Elimination Half-Life (t1/2) of Fosigotifator [ Time Frame: Baseline up to approximately Week 96 ]

Central Contacts and Locations

Central contacts

Locations

Massachusetts General Hospital /ID# 270960

Recruiting

Boston, Massachusetts, United States, 02114

Children's Hospital of Philadelphia

Recruiting

Philadelphia, Pennsylvania, United States, 19104

University of Utah /ID# 255624

Recruiting

Salt Lake City, Utah, United States, 84112-5339

McGill University Health Centre - Glen Site

Recruiting

Montreal, Quebec, Canada, H3H2L9

More Information

Sponsor

Calico Life Sciences LLC

Last update posted

Jul 1, 2026

Last verified

Jun, 2026

Keywords

  • Neurodegenerative Diseases
  • Nervous System Diseases
  • Central Nervous System Brain Diseases
  • Hereditary Central Nervous System
  • Leukoencephalopathy with Vanishing White Matter

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Calico Life Sciences LLC on 2026-07-01.