A Clinical Trial to Learn About the Effects of VHB937 in People With Amyotrophic Lateral Sclerosis (ALS)

Phase 2Active Not RecruitingNCT06643481

Novartis Pharmaceuticals251 enrolled

Overview

This is a multicenter, randomized, double-blind, placebo-controlled, parallel group Phase II study to evaluate the efficacy and safety of VHB937 in participants with early-stage ALS (within 2 years of ALS symptoms onset). The study comprises a core double-blind (DB) 40-week treatment period followed by an open label extension (OLE).

The main questions this trial aims to answer in comparing VHB937 to placebo are: * How long will participants live without needing permanent help from a machine to breathe after starting the trial treatment? * What is the change in the participant's ability to perform daily activities? This will be measured using a questionnaire called the amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R). * What adverse events are reported during this trial? An adverse event is any sign or symptom that participants have during a trial. Adverse events may or may not be caused by treatments in the trial. The trial doctors will check participants' ALS and general health throughout the trial.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

251

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Interventions

VHB937BIOLOGICAL

VHB937 solution for infusion

PlaceboOTHER

Solution for infusion

Eligibility

Sex: ALLMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

Inclusion Criteria: * are 18 years of age or older * male or female, if of childbearing potential, strict contraception required * have ALS confirmed by the trial doctors using different tests. * have mild symptoms of ALS as measured by the ALSFRS-R questionnaire (total score \>=30). * have had symptoms of ALS (weakness) within 24 months of taking part in this trial. * have not received treatment for ALS or are currently on a stable dose of an approved treatment for ALS. * have the ability to slowly exhale a volume of air at least 60% of what is expected for the participant's sex, height and age. Exclusion Criteria: * Use of other investigational drugs within 5 half-lives of screening, or within 30 days (e.g., small molecules) / or until the expected pharmacodynamic effect has returned to baseline (e.g., biologics), whichever is longer; or longer if required by local regulations. * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 24 weeks after stopping study medication. * History or current diagnosis of cardiac conditions or ECG abnormalities indicating significant risk of safety for participants in the study. * Clinical evidence of liver or renal disease/injury. * Laboratory evidence of hematological abnormalities * Presence of unstable psychiatric disease, cognitive impairment, neurological disease other than ALS, dementia or substance abuse that would impair ability of the participant to provide informed consent, in the investigator's opinion. * Participants that reported 'yes' on any suicidal ideation section except for the "Non-Suicidal Self-Injurious Behavior" in the past 2 years as per C-SSRS. * Presence of cancer, HIV, Hep B, Hep C, tuberculosis, uncontrolled diabetes * History of active severe respiratory disease, including Chronic Obstructive Pulmonary Disease, interstitial lung disease or pulmonary fibrosis. * Taking any prohibited medications

Locations (74)

Outcomes

Primary Outcomes

The composite of PAV-free survival and change in ALSFRS-R. Analysis method: Combined Assessment of Function and Survival (CAFS)

To compare the efficacy of VHB937 vs. placebo on a composite of permanent assisted ventilation (PAV) free survival and function in DB epoch

Time frame: Baseline to DB Week 40

Secondary Outcomes

ALS Functional Rating Scale Revised (ALSFRS-R) total score

To assess the efficacy of VHB937 on functional decline in DB and OLE epochs.

Time frame: Baseline to DB Week 40 or until death or PAV (whichever occurs first) and Baseline to OLE Week 100 or until death or PAV (whichever occurs first

Slow Vital Capacity (SVC) (% of predicted normal value)

To assess the efficacy of VHB937 in delaying decline in respiratory function in DB and OLE epochs.

Time frame: Baseline to DB Week 40 or until death or PAV (whichever occurs first) and Baseline to OLE Week 100 or until death or PAV (whichever occurs first)

Ratio to baseline in Neurofilament Light (NfL) concentration in serum

To assess the effect of VHB937 on a biomarker of neurodegeneration in DB and OLE epochs.

Time frame: DB up to Week 40; DB and OLE up to Week 100]

Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

To assess the safety and tolerability of VHB937 in DB and OLE epochs.

Time frame: Baseline to end of study

Time to death and Time to event (death or PAV, whichever comes first).

To assess the efficacy of VHB937 vs. placebo on survival endpoints in DB epoch.

Time frame: Baseline to DB Week 40

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

University of California San Diego

La Jolla, California, United States

Loma Linda University Health

Loma Linda, California, United States

Keck Medical Center USC

Los Angeles, California, United States

UC San Francisco Medical Center

San Francisco, California, United States

University of Miami

Miami, Florida, United States

Orlando Health Clinical Trials

Orlando, Florida, United States

Emory University School of Medicine

Atlanta, Georgia, United States

University Of Kansas Medical Center

Kansas City, Kansas, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

...and 64 more locations