ABBV-CLS-7262 for Vanishing White Matter Disease

Recruiting at 8 trial locations

Overseen By Call Center - English

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AbbVie

Disqualifiers: Respiratory support, Uncontrolled seizures, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 201 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug called Fosigotifator (also known as ABBV-CLS-7262) to determine its effectiveness for people with Vanishing White Matter (VWM) disease, a rare brain condition causing symptoms like movement and cognitive difficulties. Participants will attend regular visits to monitor health and any side effects from the treatment. Individuals diagnosed with VWM disease who have experienced neurological symptoms, such as difficulty walking or significant cognitive challenges, might be suitable candidates. As a Phase 1 and Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants the chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions that changes in medication use for managing VWM disease symptoms within 4 weeks before screening are not allowed. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that Fosigotifator, the drug being tested for Vanishing White Matter disease, is generally safe. Patients have tolerated it well, with only minor side effects reported. This is encouraging for those considering joining the trial, as previous research suggests the drug is safe. Current studies aim to confirm this safety and assess its effectiveness in treating the disease. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Fosigotifator because it offers a fresh approach to treating Vanishing White Matter Disease (VWM), a rare and serious condition. Unlike traditional symptomatic treatments that mainly manage the effects of VWM, Fosigotifator targets the underlying mechanisms of the disease. This drug aims to address the root cause by potentially stabilizing or repairing the white matter in the brain, which is crucial for effective communication between brain cells. This novel mechanism of action could lead to more durable improvements in patient outcomes, which is a significant advancement over existing options.

What evidence suggests that this treatment might be an effective treatment for Vanishing White Matter disease?

Research has shown that fosigotifator, also known as ABBV-CLS-7262, may help treat Vanishing White Matter (VWM) disease. This trial will evaluate fosigotifator across different age groups, with participants divided into cohorts based on age. The drug activates a protein called eIF2B, which helps cells survive and respond to stress. Early studies found that healthy volunteers tolerated it well for up to 14 days, suggesting it might be safe for longer use. Although limited information exists on its effectiveness for VWM in humans, its mechanism suggests it could help manage this condition. ^{1 2 3 4 6}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults diagnosed with Vanishing White Matter disease, confirmed by a physician and MRI, who have a caregiver to assist them. Participants must be able to consent or have someone who can legally do so on their behalf. They should not have changed VWM medications in the last 4 weeks or received other investigational treatments recently. Adequate contraception is required for sexually active participants.

Inclusion Criteria

Signed and dated informed consent provided by the subject, or from a legally authorized representative (LAR) if subject is incapable to consent themselves

I have been diagnosed with VWM disease by a doctor, confirmed through genetic testing and MRI results.

I have someone who can help me and complete caregiver assessments.

Exclusion Criteria

I am unable to attend all required study visits and procedures.

Pregnant or breastfeeding

Treatment with any other investigational treatment within 30 days or 5 half-lives (whichever is longer) prior to Baseline

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Fosigotifator and attend regular visits for medical assessments, blood tests, questionnaires, and evaluation for side effects

201 weeks

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ABBV-CLS-7262

Trial Overview The trial tests ABBV-CLS-7262's safety and how the body processes it over a period of 96 weeks in patients with Vanishing White Matter disease. It's an open-label study, meaning everyone knows they're getting the drug, without any comparison group.

How Is the Trial Designed?

Group I: Fosigotifator - Cohort 4 Experimental Treatment 1 Intervention

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

Group II: Fosigotifator - Cohort 3 Experimental Treatment 1 Intervention

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

Group III: Fosigotifator - Cohort 2 Experimental Treatment 1 Intervention

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

Group IV: Fosigotifator - Cohort 1b Experimental Treatment 1 Intervention

Cohort 1b: VWM adults \>= 18 years.

Group V: Fosigotifator - Cohort 1 Experimental Treatment 1 Intervention

Cohort 1: VWM adults \>= 18 years.

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Calico Life Sciences LLC

Lead Sponsor

Trials

11

Recruited

960+

Published Research Related to This Trial

Fingolimod effectively prevented the progression of experimental autoimmune optic neuritis (EAON) in mice, showing only minimal decline in visual acuity compared to a significant decline in the control group.

The treatment was effective even when started after the onset of optic neuritis symptoms, indicating its potential as a therapeutic option for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppression of experimental autoimmune optic neuritis by the novel agent fingolimod. An, X., Kezuka, T., Usui, Y., et al.[2015]

In a study of 42 patients, including 32 with atypical variants of multiple sclerosis (MS) and 10 with acute disseminated encephalomyelitis (ADEM), it was found that levels of specific antibodies (AQP1-IgG, AQP4-IgG, and MOG-IgG) were significantly higher in patients compared to healthy controls, indicating a potential role in the disease process.

A correlation was observed between high levels of MOG-IgG and increased disability (measured by EDSS scores) in patients with Balo's concentric sclerosis (BCS), suggesting that MOG-IgG may be important in understanding the pathology of this atypical MS variant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical and biochemical characteristics of atypical variants of multiple sclerosis]. Shchepareva, ME., Skalnaya, AA., Zakharova, MN., et al.[2020]

FTY720 (fingolimod) is an oral medication that shows promise in treating both relapsing-remitting and progressive forms of multiple sclerosis (MS) by affecting the immune system and potentially providing neuroprotection within the central nervous system (CNS).

Unlike other MS treatments, FTY720 can cross the blood-brain barrier, allowing it to directly influence brain cells involved in immune regulation and repair, which may enhance its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Central nervous system-directed effects of FTY720 (fingolimod). Miron, VE., Schubart, A., Antel, JP.[2015]

Fingolimod (FTY720) promotes myelination in the central nervous system but, at higher concentrations, it can induce apoptosis in Schwann cells, which are crucial for peripheral nerve myelination.

The study found that FTY720P treatment led to a significant reduction in myelin formation and increased reactive oxygen species in Schwann cells, indicating that while it has therapeutic potential, it may also have detrimental effects on peripheral nerve health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fingolimod impedes Schwann cell-mediated myelination: implications for the treatment of immune neuropathies? Köhne, A., Stettner, M., Jangouk, P., et al.[2015]

In a study involving 88 healthy volunteers, fingolimod doses of 0.5 mg and 1.25 mg did not significantly alter cerebral blood flow, platelet function, or macular thickness compared to placebo, indicating a safety profile consistent with previous reports.

The changes observed in blood flow and other parameters were within normal variability, suggesting that fingolimod does not have adverse effects on these measures in healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of fingolimod (FTY720) on cerebral blood flow, platelet function and macular thickness in healthy volunteers. Ocwieja, M., Meiser, K., David, OJ., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05757141

Study Details | NCT05757141 | An Open-Label Exploratory ... This is a 201-week, open-label, multiple cohort study enrolling adults, pediatric and infant participants with Vanishing White Matter disease.

2. abbvieclinicaltrials.com abbvieclinicaltrials.com/study/?id=M23-523

An Open-Label Exploratory Study of Fosigotifator in ... Fosigotifator is an investigational drug being researched for the treatment of Vanishing White Matter disease in adult, pediatric and infant participants.

3. trial.medpath.com trial.medpath.com/drug/report/86892eab963fd37d

ABBV-CLS-7262 | Advanced Drug Monograph - MedPath Comprehensive analysis about ABBV-CLS-7262, including its mechanisms, clinical uses, and therapeutic considerations.

4. bioworld.com bioworld.com/articles/707776-eif2b-activator-abbv-cls-7262-shows-promise-in-vanishing-white-matter-disease

eIF2B activator ABBV-CLS-7262 shows promise in ... The compound is currently in phase I trials for VWM and was well tolerated following dosing for up to 14 days in healthy volunteers.

5. calicolabs.com calicolabs.com/press/calico-life-sciences-announces-that-fosigotifator-abbv-cls-7262-for-vanishing-white-matter-disease-has-been-selected-for-the-fda-start-pilot-program/

Calico Life Sciences Announces that Fosigotifator (ABBV-CLS ... Fosigotifator is being developed by Calico and AbbVie pursuant to their 2014 collaboration as a potential treatment for Vanishing White Matter (VWM) disease.

6. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effects-of-fosigotifator-in-adults-and-children-with-vanishing-white-matter-disease/

Study on the Safety and Effects of Fosigotifator in Adults ... The purpose of the study is to evaluate the safety and tolerability of Fosigotifator in patients with Vanishing White Matter disease.