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

NCT06643481 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: CVHB937B122012024-512536-29-00
• Study Type: interventional
• Target: 251
• Locations: 17 countries
• Sites: 74

Brief Summary

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).

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Keywords

Amyotrophic Lateral Sclerosis; ALS; monoclonal antibody; motor neuron disease; MND

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline to DB Week 40

Secondary Outcomes (18)

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

  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)

  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

  DB up to Week 40; DB and OLE up to Week 100]

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

  Baseline to end of study

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

  Baseline to DB Week 40

Study Arms (2)

Arm 1

EXPERIMENTAL

I.V. infusions

Biological: VHB937

Arm 2

PLACEBO COMPARATOR

I.V. infusions

Other: Placebo

Interventions

VHB937 BIOLOGICAL

VHB937 solution for infusion

Arm 1

Placebo OTHER

Solution for infusion

Arm 2

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (74)

University of California San Diego

La Jolla, California, 92037, United States

Location

Loma Linda University Health

Loma Linda, California, 92354, United States

Location

Keck Medical Center USC

Los Angeles, California, 90033, United States

Location

UC San Francisco Medical Center

San Francisco, California, 94143-0348, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Orlando Health Clinical Trials

Orlando, Florida, 32806, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

University Of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Lange Neurology PC

New York, New York, 10065, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Atrium Health

Charlotte, North Carolina, 28207, United States

Location

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Univ of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

AMR Knoxville

Knoxville, Tennessee, 37920, United States

Location

Austin Neuromuscular Center

Austin, Texas, 78759, United States

Location

Nerve and Muscle Center of Texas

Houston, Texas, 77030, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Novartis Investigative Site

North Ryde, New South Wales, 2109, Australia

Location

Novartis Investigative Site

Herston, Queensland, 4029, Australia

Location

Novartis Investigative Site

Caulfield South, Victoria, 3162, Australia

Location

Novartis Investigative Site

Southport, 4215, Australia

Location

Novartis Investigative Site

Leuven, Vlaams Brabant, 3000, Belgium

Location

Novartis Investigative Site

Liège, 4000, Belgium

Location

Novartis Investigative Site

Calgary, Alberta, T2N 4N1, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H4A 3T2, Canada

Location

Novartis Investigative Site

Beijing, 100191, China

Location

Novartis Investigative Site

Aalborg, 9000, Denmark

Location

Novartis Investigative Site

Kobenhavn N V, 2400, Denmark

Location

Novartis Investigative Site

Bron, 69677, France

Location

Novartis Investigative Site

Lille, 59037, France

Location

Novartis Investigative Site

Nice, 06001, France

Location

Novartis Investigative Site

Paris, 75013, France

Location

Novartis Investigative Site

Tours, 37044, France

Location

Novartis Investigative Site

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

Novartis Investigative Site

Munich, Bavaria, 81675, Germany

Location

Novartis Investigative Site

Würzburg, Bavaria, 97080, Germany

Location

Novartis Investigative Site

Rostock, Mecklenburg-Vorpommern, 18057, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Hanover, 30559, Germany

Location

Novartis Investigative Site

Lübeck, 23538, Germany

Location

Novartis Investigative Site

Münster, 48149, Germany

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Novartis Investigative Site

Dublin, DUBLIN 9, Ireland

Location

Novartis Investigative Site

Milan, MI, 20138, Italy

Location

Novartis Investigative Site

Modena, MO, 41126, Italy

Location

Novartis Investigative Site

Pisa, PI, 56126, Italy

Location

Novartis Investigative Site

Torino, TO, 10126, Italy

Location

Novartis Investigative Site

Utrecht, 3584 CX, Netherlands

Location

Novartis Investigative Site

Bydgoszcz, 85-163, Poland

Location

Novartis Investigative Site

Krakow, 30-721, Poland

Location

Novartis Investigative Site

Krakow, 31 531, Poland

Location

Novartis Investigative Site

Warsaw, 01-684, Poland

Location

Novartis Investigative Site

Warsaw, 02-473, Poland

Location

Novartis Investigative Site

Yangsan, Gyeongsangnam-do, 50612, South Korea

Location

Novartis Investigative Site

Seoul, 04763, South Korea

Location

Novartis Investigative Site

Seoul, 05505, South Korea

Location

Novartis Investigative Site

Santiago Compostela, A Coruna, 15706, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Novartis Investigative Site

Barcelona, 08035, Spain

Location

Novartis Investigative Site

Valencia, 46026, Spain

Location

Novartis Investigative Site

Malmö, 214 28, Sweden

Location

Novartis Investigative Site

Stockholm, 113 61, Sweden

Location

Novartis Investigative Site

Umeå, SE-90185, Sweden

Location

Novartis Investigative Site

Basel, 4031, Switzerland

Location

Novartis Investigative Site

Sankt Gallen, 9007, Switzerland

Location

Novartis Investigative Site

Sheffield, South Yorkshire, S10 2JF, United Kingdom

Location

Novartis Investigative Site

Farnborough, BR6 8ND, United Kingdom

Location

Novartis Investigative Site

London, SW17 0QT, United Kingdom

Location

Novartis Investigative Site

London, WC1N 3BG, United Kingdom

Location

Novartis Investigative Site

Stoke-on-Trent, ST4 6QG, United Kingdom

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinded placebo for infusion
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double-blind, Randomized 2:1 ratio

Study Record Dates

• First Submitted: September 30, 2024
• First Posted: October 16, 2024
• Study Start: October 17, 2024
• Primary Completion (Estimated): September 21, 2026
• Study Completion (Estimated): July 10, 2028
• Last Updated: May 19, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

KR (3); BE (2); NL (1); GB (5); AU (4); IT (4); PL (5); IE (1); DK (2); CA (2); US (21); DE (9); ES (4); SE (3); CN (1); CH (2); FR (5)