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

A Phase 2, Randomized, Double-blind, Placebo-controlled Parallel Group Study of VHB937 in Amyotrophic Lateral Sclerosis (ALS) Over 40 Weeks Followed by an Open Label Extension (ASTRALS)

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Amyotrophic Lateral Sclerosis (ALS)
• Intervention / Treatment: Other: Placebo; Biological: VHB937

Detailed Description

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
• Enrollment (Actual): 251
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Southport, Australia, 4215
    • Novartis Investigative Site
  • New South Wales
    • North Ryde, New South Wales, Australia, 2109
      • Novartis Investigative Site
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Novartis Investigative Site
  • Victoria
    • Caulfield South, Victoria, Australia, 3162
      • Novartis Investigative Site
• Belgium
  • Liège, Belgium, 4000
    • Novartis Investigative Site
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • Novartis Investigative Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H4A 3T2
      • Novartis Investigative Site
• China
  • Beijing, China, 100191
    • Novartis Investigative Site
• Denmark
  • Aalborg, Denmark, 9000
    • Novartis Investigative Site
  • Kobenhavn N V, Denmark, 2400
    • Novartis Investigative Site
• France
  • Bron, France, 69677
    • Novartis Investigative Site
  • Lille, France, 59037
    • Novartis Investigative Site
  • Nice, France, 06001
    • Novartis Investigative Site
  • Paris, France, 75013
    • Novartis Investigative Site
  • Tours, France, 37044
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Hanover, Germany, 30559
    • Novartis Investigative Site
  • Lübeck, Germany, 23538
    • Novartis Investigative Site
  • Münster, Germany, 48149
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
  • Baden-Wurttemberg
    • Mannheim, Baden-Wurttemberg, Germany, 68167
      • Novartis Investigative Site
  • Bavaria
    • Munich, Bavaria, Germany, 81675
      • Novartis Investigative Site
    • Würzburg, Bavaria, Germany, 97080
      • Novartis Investigative Site
  • Mecklenburg-Vorpommern
    • Rostock, Mecklenburg-Vorpommern, Germany, 18057
      • Novartis Investigative Site
• Ireland
  • Dublin, Ireland, DUBLIN 9
    • Novartis Investigative Site
• Italy
  • MI
    • Milan, MI, Italy, 20138
      • Novartis Investigative Site
  • MO
    • Modena, MO, Italy, 41126
      • Novartis Investigative Site
  • PI
    • Pisa, PI, Italy, 56126
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10126
      • Novartis Investigative Site
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • Novartis Investigative Site
• Poland
  • Bydgoszcz, Poland, 85-163
    • Novartis Investigative Site
  • Krakow, Poland, 31 531
    • Novartis Investigative Site
  • Krakow, Poland, 30-721
    • Novartis Investigative Site
  • Warsaw, Poland, 01-684
    • Novartis Investigative Site
  • Warsaw, Poland, 02-473
    • Novartis Investigative Site
• South Korea
  • Seoul, South Korea, 05505
    • Novartis Investigative Site
  • Seoul, South Korea, 04763
    • Novartis Investigative Site
  • Gyeongsangnam-do
    • Yangsan, Gyeongsangnam-do, South Korea, 50612
      • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08035
    • Novartis Investigative Site
  • Valencia, Spain, 46026
    • Novartis Investigative Site
  • A Coruna
    • Santiago Compostela, A Coruna, Spain, 15706
      • Novartis Investigative Site
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Novartis Investigative Site
• Sweden
  • Malmö, Sweden, 214 28
    • Novartis Investigative Site
  • Stockholm, Sweden, 113 61
    • Novartis Investigative Site
  • Umeå, Sweden, SE-90185
    • Novartis Investigative Site
• Switzerland
  • Basel, Switzerland, 4031
    • Novartis Investigative Site
  • Sankt Gallen, Switzerland, 9007
    • Novartis Investigative Site
• United Kingdom
  • Farnborough, United Kingdom, BR6 8ND
    • Novartis Investigative Site
  • London, United Kingdom, SW17 0QT
    • Novartis Investigative Site
  • London, United Kingdom, WC1N 3BG
    • Novartis Investigative Site
  • Stoke-on-Trent, United Kingdom, ST4 6QG
    • Novartis Investigative Site
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2JF
      • Novartis Investigative Site
• United States
  • California
    • La Jolla, California, United States, 92037
      • University Of California San Diego
    • Loma Linda, California, United States, 92354
      • Loma Linda University Health
    • Los Angeles, California, United States, 90033
      • Keck Medical Center USC
    • San Francisco, California, United States, 94143-0348
      • UC San Francisco Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Orlando, Florida, United States, 32806
      • Orlando Health Clinical Trials
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10065
      • Lange Neurology PC
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Atrium Health
    • Durham, North Carolina, United States, 27710
      • Duke University Health System
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Univ of Cincinnati Medical Center
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • AMR Knoxville
  • Texas
    • Austin, Texas, United States, 78759
      • Austin Neuromuscular Center
    • Houston, Texas, United States, 77030
      • Nerve And Muscle Center Of Texas
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; I.V. infusions	Biological: VHB937; VHB937 solution for infusion
Placebo Comparator: Arm 2; I.V. infusions	Other: Placebo; Solution for infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
ALS Functional Rating Scale Revised (ALSFRS-R) total score	To assess the efficacy of VHB937 on functional decline in DB and OLE epochs.	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.	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.	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.	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.	Baseline to DB Week 40
Time to death and Time to event (death or PAV, whichever comes first) - endpoints referring to treatment policy estimand	To assess the efficacy of early vs. delayed VHB937 administration on survival endpoints (DB VHB937 followed by OLE VHB937 vs. DB placebo followed by OLE VHB937)	Baseline to OLE Week 100, and Baseline to end of study
Patient Global Impression of change in functional ability and ALS symptom severity (PGI-C)	To assess change in ALS condition in DB and OLE epochs.	DB up to Week 40; DB and OLE up to Week 100
Change in QoL from baseline as measured with Amyotrophic Lateral Sclerosis Assessment Questionnaire -5 (ALSAQ-5)	To assess Quality of Life (QoL) with VHB937 in DB and OLE epochs.	DB up to Week 40; DB and OLE up to Week 100
Change in Clinician Global Impression of change in functional ability and ALS symptom severity (CGI-C)	To assess change in ALS condition in DB and OLE epochs.	DB up to Week 40; DB and OLE up to Week 100
Change in QoL from baseline as measured with EuroQoL 5 Dimension 5 Level (EQ-5D-5L)	To assess Quality of Life (QoL) with VHB937 in DB and OLE epochs.	DB up to Week 40; DB and OLE up to Week 100
Change in QoL from baseline as measured with 12-item Short form health survey (SF-12)	To assess Quality of Life (QoL) with VHB937 in DB and OLE epochs.	DB up to Week 40; DB and OLE up to Week 100
Pharmacokinetics (PK) of VHB937-CMAX	CMAX - The maximum concentration of VHB937 in serum	Day 1 to end of study
Pharmacokinetics (PK) of VHB937-TMAX	TMAX - The time to reach the maximum concentration of VHB937 in serum	Day 1 to end of study
Pharmacokinetics (PK) of VHB937-CTROUGH	CTROUGH - Minimum observed concentration of VHB937 in serum	Day 1 to end of study
Cerebralspinal Spinal Fluid Pharmacokinetics (PK) of VHB937-CMAX	CMAX - The maximum concentration of VHB937 in CSF	Screening to Week 12
Cerebralspinal Spinal Fluid Pharmacokinetics (PK) of VHB937-TMAX	TMAX - The time to reach the maximum concentration of VHB937 in CSF	Screening to Week 12
Cerebralspinal Spinal Fluid Pharmacokinetics (PK) of VHB937-CTROUGH	CTROUGH - Minimum observed concentration of VHB937 in CSF	Screening to Week 12
To assess immunogenicity (IG) of VHB937	To assess immunogenicity of Anti-VHB937 antibodies in serum	Day 1 up to end of study

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2024
• Primary Completion (Estimated): September 21, 2026
• Study Completion (Estimated): July 10, 2028

Study Registration Dates

• First Submitted: September 30, 2024
• First Submitted That Met QC Criteria: October 12, 2024
• First Posted (Actual): October 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; ALS; monoclonal antibody; motor neuron disease; MND
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Nutritional and Metabolic Diseases; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: CVHB937B12201; 2024-512536-29-00 (Other Identifier: EUCTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No