A Study of VRG50635 in Participants With Amyotrophic Lateral Sclerosis (ALS)

NCT06215755 | Terminated Phase 1 DMC

• 2 other identifiers: VGCS-50635-0022023-506509-21
• Study Type: interventional
• Target: 54
• Locations: 4 countries
• Sites: 7

Brief Summary

The primary purpose of this study is to evaluate the safety and tolerability of VRG50635 in participants with ALS.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

VRG50635; Familial Amyotrophic Lateral Sclerosis; Sporadic Amyotrophic Lateral Sclerosis; ALS

Outcome Measures

Primary Outcomes (6)

• Number of Participants with Treatment-emergent Adverse Events (TEAEs)

  Up to 80 weeks

• Number of Participants with Clinical Laboratory Evaluation Abnormalities

  Up to 80 weeks

• Number of Participants with Vital Sign Abnormalities

  Up to 80 weeks

• Number of Participants with Electrocardiogram (ECG) Abnormalities

  Up to 80 weeks

• Number of Participants with Physical Examination Abnormalities

  Up to 80 weeks

• Number of Participants with Neurological Examination Abnormalities

  Up to 80 weeks

Secondary Outcomes (6)

• Maximum Observed Concentration (Cmax)

  Up to 80 weeks

• Area Under the Concentration-time Curve (AUC)

  Up to 80 weeks

• Time to Maximum Observed Concentration (tmax)

  Up to 80 weeks

• Change from Baseline in Plasma Levels of Neurofilament Light Chain (NfL) as Measured by Immunoassay

  Baseline, up to 80 weeks

• Time to Disease Progression

  Up to 80 weeks

Study Arms (1)

VRG50635

EXPERIMENTAL

The study drug is VRG50635 200 mg oral capsules. VRG50635 will be administered as oral capsules once daily in the morning after a low-fat meal, approximately 30 minutes prior to VRG50635 administration. Following administration there is a 5 to 6-hour restriction period where participants should consume only low-fat food.

Drug: VRG50635

Interventions

VRG50635 DRUG

Part 1, no study drug will be administered. Part 2, the starting dose is 400 mg for 8 weeks (Treatment Period 1) and doses will be escalated to 600 mg for 8 weeks (Treatment Period 2) and 800 mg for 8 weeks (Treatment Period 3). Part 3, each participant will continue receiving treatment with the highest tolerated dose achieved in Part 2 for up to 40 weeks.

VRG50635

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written informed consent and be willing and able to comply with the requirements of the study protocol.
• Must be ≥ 18 and ≤ 75 years of age at the time of signing the informed consent form (ICF).
• Have a diagnosis of ALS according to the Gold Coast Diagnostic Criteria.
• Have either sporadic amyotrophic lateral sclerosis (sALS) or familial amyotrophic lateral sclerosis (fALS).
• Treatment Research Initiative to Cure ALS (TRICALS) risk profile \> -6.00 and \< -2.00.
• Have slow vital capacity (SVC) ≥ 60% of the predicted value.
• Have a score of 3 or 4 on Item #3 (Swallowing) of the Harmonized ALS Functional Rating Scale-Revised (ALS-FRS-R). Participants with a score of 3 can be enrolled with the Sponsor's approval only if they are able to safely swallow capsules.
• Have a body weight ≥ 45 kg and body mass index (BMI) ≥ 18 kg/m2.
• Participants of childbearing potential are eligible to participate if they are not pregnant or breastfeeding and agree to use one highly effective method of contraception, if sexually active, for the duration of the study through 90 days after the last study drug administration. Participants must not donate eggs for the duration of study through 90 days after the last dose of study drug.
• Participants capable of producing sperm and their partners of childbearing potential must agree to use condoms and one highly effective method of contraception, respectively, for the duration of the study through 90 days after the last study drug administration. Participants must not donate sperm for the duration of study through 90 days after the last dose of study drug.
• Be able and willing to undergo measurement of at-home mobility using contactless sensors connected to the internet.
• Be able and willing to have clinic or at-home visits during the study.

You may not qualify if:

• Have active psychiatric disease, substance abuse, neuromuscular weakness other than ALS, or any other medical condition that, in the opinion of the Investigator, might confound the results of the study or interfere with the intake or absorption of the study drug or participation for the full duration of the study.
• Have a history of unstable or severe cardiac, pulmonary, neurological, oncological, hepatic, or renal disease or another medically significant illness other than ALS precluding their safe participation in this study.
• Have a history of substance use disorder or illicit drug use in the last year (medically prescribed or over-the-counter cannabis use is allowed, if legal in the country).
• Have a history of serious infection (e.g., pneumonia, septicemia) ≤ 4 weeks of Screening; infection requiring hospitalization or treatment with intravenous (IV) antibiotics, antivirals, or antifungals within 4 weeks of Screening; or chronic bacterial infection (e.g., tuberculosis) deemed unacceptable as per the Investigator's judgment.
• Had major surgery ≤ 4 weeks before Screening.
• Be currently taking or planning to take strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers.
• Be currently taking or have discontinued treatment with riluzole \< 4 weeks before Screening. Participants who have been taking a stable dose of riluzole for ≥ 4 weeks are eligible if they remain on the same dose throughout the duration of the study.
• Be taking Radicava (administered orally or IV as approved in the participant's country), Relyvrio, any other approved standard of care treatment, or tauroursodeoxycholic acid (TUDCA) as a dietary supplement administered for \< 4 weeks prior to Screening or on a schedule of treatment different from the approved standard schedule of treatment. Participants who have completed ≥ 4 weeks of treatment before Screening are eligible if they plan to continue treatment at a stable dose throughout the duration of the study.
• Have an active malignancy or history (≤ 1 years prior to enrollment) of solid, metastatic, or hematologic malignancy. Exception: basal cell carcinoma in situ of the skin that has been adequately treated.
• Be diagnosed with long QT syndrome. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes) should be discussed with and approved by the study medical monitor prior to enrollment.
• Have a prolonged corrected QT interval using Fridericia's formula (QTcF) at the Screening visit ECG \> 450 ms for male participants and \> 470 ms for female participants.
• Have an active SARS-CoV-2 infection or positive COVID-19 test at Screening.1
• Have one or more of the following laboratory test abnormalities at Screening: (a) Positive hepatitis C virus (HCV) antibodies with confirmation by HCV-RNA polymerase chain reaction (PCR) reflex testing; (b) Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Note: If a participant is negative for HBsAg but positive for HBcAb, the participant is eligible if the participant tests positive for the antibody to HBsAg reflex testing.
• Have uncontrolled seizures.
• Have a documented history of attempted suicide within 6 months prior to the Screening visit, or suicidal ideation of category 4 or 5 on the screening Columbia-Suicide Severity Rating Scale (C-SSRS), or be at significant risk for suicide, in the opinion of the Investigator.

Sponsors & Collaborators

• Verge Genomics: lead

Study Sites (7)

UZ Leuven

Leuven, Flemish Brabant, Belgium

Location

Stan Cassidy Centre for Rehabilitation (Horizon NB)

Montreal, Quebec, H3A 2B4, Canada

Location

The Neuro - Montréal Neurological Institute-Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

University of Eastern Finland, Brain Research Unit

Kuopio, Eastern Finland, FI-70210, Finland

Location

Helsinki University Hospital

Helsinki, Uusimaa, FI-00029, Finland

Location

Turku University Hospital

Turku, Western Finland, FI-20520, Finland

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Related Publications (2)

• Hung ST, Linares GR, Chang WH, Eoh Y, Krishnan G, Mendonca S, Hong S, Shi Y, Santana M, Kueth C, Macklin-Isquierdo S, Perry S, Duhaime S, Maios C, Chang J, Perez J, Couto A, Lai J, Li Y, Alworth SV, Hendricks E, Wang Y, Zlokovic BV, Dickman DK, Parker JA, Zarnescu DC, Gao FB, Ichida JK. PIKFYVE inhibition mitigates disease in models of diverse forms of ALS. Cell. 2023 Feb 16;186(4):786-802.e28. doi: 10.1016/j.cell.2023.01.005. Epub 2023 Feb 7.

  PMID: 36754049 BACKGROUND

• Shi Y, Lin S, Staats KA, Li Y, Chang WH, Hung ST, Hendricks E, Linares GR, Wang Y, Son EY, Wen X, Kisler K, Wilkinson B, Menendez L, Sugawara T, Woolwine P, Huang M, Cowan MJ, Ge B, Koutsodendris N, Sandor KP, Komberg J, Vangoor VR, Senthilkumar K, Hennes V, Seah C, Nelson AR, Cheng TY, Lee SJ, August PR, Chen JA, Wisniewski N, Hanson-Smith V, Belgard TG, Zhang A, Coba M, Grunseich C, Ward ME, van den Berg LH, Pasterkamp RJ, Trotti D, Zlokovic BV, Ichida JK. Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons. Nat Med. 2018 Mar;24(3):313-325. doi: 10.1038/nm.4490. Epub 2018 Feb 5.

  PMID: 29400714 BACKGROUND

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Amyotrophic lateral sclerosis 1

Condition Hierarchy (Ancestors)

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

Study Officials

• Diego Cadavid, MD

  Verge Genomics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1, no study drug will be administered. Part 2, the starting dose is 400 mg for 8 weeks (Treatment Period 1) and doses will be escalated to 600 mg for 8 weeks (Treatment Period 2) and 800 mg for 8 weeks (Treatment Period 3). Part 3, each participant will continue receiving treatment with the highest tolerated dose achieved in Part 2 for up to 40 weeks.

Study Record Dates

• First Submitted: December 18, 2023
• First Posted: January 22, 2024
• Study Start: January 15, 2024
• Primary Completion: July 7, 2025
• Study Completion: July 7, 2025
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); NL (1); FI (3); CA (2)