Clinical trial NCT06643481: A Clinical Trial to Learn About the Effects of VHB937 in People With Amyotrophic Lateral Sclerosis (ALS)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis (ALS)
Keywords: Amyotrophic Lateral Sclerosis
ALS
monoclonal antibody
motor neuron disease
MND
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2024-10-16
Enrollment: 225
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, Randomized 2:1 ratio
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: The composite of PAV-free survival and change in ALSFRS-R. Analysis method: Combined Assessment of Function and Survival (CAFS)
timeFrame: Baseline to DB Week 40
Secondary outcomes:
measure: ALS Functional Rating Scale Revised (ALSFRS-R) total score
timeFrame: 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
measure: Slow Vital Capacity (SVC) (% of predicted normal value)
timeFrame: 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)
measure: Ratio to baseline in Neurofilament Light (NfL) concentration in serum
timeFrame: DB up to Week 40; DB and OLE up to Week 100]
measure: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline to end of study
measure: Time to death and Time to event (death or PAV, whichever comes first).
timeFrame: Baseline to DB Week 40
measure: Time to death and Time to event (death or PAV, whichever comes first) - endpoints referring to treatment policy estimand
timeFrame: Baseline to OLE Week 100, and Baseline to end of study
measure: Patient Global Impression of change in functional ability and ALS symptom severity (PGI-C)
timeFrame: DB up to Week 40; DB and OLE up to Week 100
measure: Change in QoL from baseline as measured with Amyotrophic Lateral Sclerosis Assessment Questionnaire -5 (ALSAQ-5)
timeFrame: DB up to Week 40; DB and OLE up to Week 100
measure: Change in Clinician Global Impression of change in functional ability and ALS symptom severity (CGI-C)
timeFrame: DB up to Week 40; DB and OLE up to Week 100
measure: Change in QoL from baseline as measured with EuroQoL 5 Dimension 5 Level (EQ-5D-5L)
timeFrame: DB up to Week 40; DB and OLE up to Week 100
measure: Change in QoL from baseline as measured with 12-item Short form health survey (SF-12)
timeFrame: DB up to Week 40; DB and OLE up to Week 100
measure: Pharmacokinetics (PK) of VHB937-CMAX
timeFrame: Day 1 to end of study
measure: Pharmacokinetics (PK) of VHB937-TMAX
timeFrame: Day 1 to end of study
measure: Pharmacokinetics (PK) of VHB937-CTROUGH
timeFrame: Day 1 to end of study
measure: To assess immunogenicity (IG) of VHB937
timeFrame: Day 1 up to end of study
measure: Cerebralspinal Spinal Fluid Pharmacokinetics (PK) of VHB937-CMAX
timeFrame: Screening to Week 12
measure: Cerebralspinal Spinal Fluid Pharmacokinetics (PK) of VHB937-TMAX
timeFrame: Screening to Week 12
measure: Cerebralspinal Spinal Fluid Pharmacokinetics (PK) of VHB937-CTROUGH
timeFrame: Screening to Week 12
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Health Clinical Trials
state: Florida
city: Houston
country: United States
facility: Nerve and Muscle Center of Texas
state: Texas
city: Cauldfield
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: