A Study of VRG50635 in Healthy Volunteers

NCT06286475 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: VGCS-50635-003
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objectives of this study are to investigate the safety and tolerability of VRG50635 and to determine how VRG50635 is absorbed by the body.

Conditions

Healthy Volunteers

Keywords

Amyotrophic lateral sclerosis; ALS

Outcome Measures

Primary Outcomes (8)

• Number of Participants with Adverse Events

  Up to Day 30

• Area Under the Concentration-time Curve from Time 0 Extrapolated to Infinity (AUCinf)

  Up to Day 16

• Area Under the Concentration-time Curve from Time 0 to the Last Measurable Concentration (AUClast)

  Up to Day 16

• Area Under the Concentration-time Curve from Time 0 to 24 Hours Post-dose (AUC0-24)

  Up to Day 16

• Area Under the Concentration-time Curve Between Consecutive Doses (AUCtau)

  Up to Day 16

• Maximum Observed Concentration (Cmax)

  Up to Day 16

• Half-life (t1/2)

  Up to Day 16

• Time of Maximal Plasma Concentration (tmax)

  Up to Day 16

Study Arms (6)

Part 1: VRG50635 Sequence A, B, C

EXPERIMENTAL

Participants will receive a single dose of VRG50635 in each of 3 treatment periods separated by 14-day washout periods.

Drug: VRG50635

Part 1: VRG50635 Sequence B, A, C

EXPERIMENTAL

Participants will receive a single dose of VRG50635 in each of 3 treatment periods separated by 14-day washout periods.

Drug: VRG50635

Part 2: Cohort 1 VRG50635

EXPERIMENTAL

Participants will receive VRG50635 (Dose X) for 14 consecutive days.

Drug: VRG50635

Part 2: Cohort 1 Placebo

PLACEBO COMPARATOR

Participants will receive VRG50635-matching placebo for 14 consecutive days.

Drug: Placebo

Part 2: Cohort 2 VRG50635

EXPERIMENTAL

Participants will receive VRG50635 (Dose Y) for 14 consecutive days.

Drug: VRG50635

Part 2: Cohort 2 Placebo

PLACEBO COMPARATOR

Participants will receive VRG50635-matching placebo for 14 consecutive days.

Drug: Placebo

Interventions

VRG50635 DRUG

Specified dose on specified days

Part 1: VRG50635 Sequence A, B, C; Part 1: VRG50635 Sequence B, A, C; Part 2: Cohort 1 VRG50635; Part 2: Cohort 2 VRG50635

Placebo DRUG

Specified dose on specified days

Part 2: Cohort 1 Placebo; Part 2: Cohort 2 Placebo

Eligibility Criteria

• Age: 19 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Must be ≥ 19 and ≤ 55 years of age at Screening.
• Must be willing and able to voluntarily give written informed consent by signing an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form prior to any study-related procedures being performed.
• Must have a body mass index ≥ 18.5 and ≤ 32 kilogram per square meter (kg/m2) and weigh ≥ 50 kg.
• Participants of childbearing potential are eligible to participate if they are not pregnant or breastfeeding and agree to use one highly effective and one barrier 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 must agree that they will use one barrier method of contraception and that their partners of childbearing potential will use one highly effective method of contraception 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.

You may not qualify if:

• Have a history of clinically significant hematologic, renal, neurologic, pancreatic, gastrointestinal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, immunological, allergic disease, or other major disorders, as determined by the PI.
• Have any surgical or medical condition that could possibly affect drug absorption (including inflammatory bowel disease, history of gastrectomy, cholecystectomy, or other gastrointestinal tract surgery except appendectomy).
• Have a current significant medical or psychiatric condition, as determined by the PI.
• Have a history of serious adverse reaction or serious hypersensitivity to any drug.
• Have, in the opinion of the PI, evidence of clinically significant hepatic or renal impairment including alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> the upper limit of normal (ULN) or bilirubin \> 1.5 × ULN. Note: Participants with Gilbert syndrome without evidence of hepatic impairment may be enrolled.
• Have a history or presence of an abnormal electrocardiogram (ECG), including, but not limited to, complete left bundle branch block, second- or third-degree heart block, evidence of prior myocardial infarction, or any other abnormality that is clinically significant in the PI's opinion or precludes accurate interpretation and calculations of cardiac intervals (e.g., QT, QRS).
• Have clinically significant abnormalities, as assessed by the PI, in laboratory tests at the screening and admission visits. Note: Participants may be rescreened at the discretion of the PI with Sponsor approval.
• Have abnormal blood pressure: supine systolic blood pressure \< 90 or \> 140 mmHg, supine diastolic blood pressure \< 50 or \> 90 mmHg, pulse rate \< 40 or \> 100 bpm, and body temperature \< 35.4 or \> 37.8 °C (\< 96 or \> 100.3 °F) at the screening and admission visits.
• Have a prolonged corrected QT interval using Fridericia's formula (QTcF) during the 12- lead ECG at Screening or pre-dose on Day 1 \> 450 ms for participants assigned male at birth and \> 470 ms for participants assigned female at birth.
• Have a hemoglobin level \< 12 g/dL (participants assigned male at birth) or \< 10.5 g/dL (participants assigned female at birth).
• Have participated in any other investigational drug study within 30 days of dosing or within 7 half-lives of the investigational product, whichever is longer, or have previously participated in the current study.
• Use any prescription medication within 7 days or 5 half-lives (whichever is longer) of the first dose administration and/or anticipated use through the follow-up visit.
• Use any over-the-counter medication (including vitamin/mineral supplements and herbal medicines, such as St. John's wort and non-standard herbal teas) within 7 days of the first dose administration and/or anticipate using through study participation and the follow-up visit.
• Receive a positive result in a SARS-CoV-2 test or a COVID-19 vaccine within 30 days prior to Screening.
• Have poor peripheral venous access.

Sponsors & Collaborators

• Verge Genomics: lead

Study Sites (1)

Lincoln Celerion Inc.,

Lincoln, Nebraska, 68502, United States

Location

Related Publications (3)

• 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

• Gontier G, Kim G, Wang C, Zhu K, Gau R, Zhang N, Naphade S, Stewart A, Schmidt MJ, Galemmo R, Shook B, Tarachandani A, Choi I, Raines S, Scannevin RH, Grievink HW, Smits LMG, Kremer PHC, Cadavid D. Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB): A Translational Pharmacodynamic Biomarker for PIKfyve Inhibition With VRG50635. Clin Transl Sci. 2026 Feb;19(2):e70489. doi: 10.1111/cts.70489.

  PMID: 41708347 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

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: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a 2-part study that includes both an open-label (Part 1) and a double-blind, placebo-controlled (Part 2) design. In Part 1, participants will be randomly assigned to receive open-label VRG50635 in 1 of 2 treatment sequences. In Part 2, participants will receive VRG50635 or placebo in a double-blind manner.

Study Record Dates

• First Submitted: February 21, 2024
• First Posted: February 29, 2024
• Study Start: February 29, 2024
• Primary Completion: March 25, 2024
• Study Completion: April 8, 2024
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)