Study to Evaluate 5-ALA Combined With CV01 Delivery of Ultrasound in Recurrent High Grade Glioma

Phase 1

Active, not recruiting

• Conditions: High Grade Glioma
• Interventions: Drug: 5 Aminolevulinic Acid; Device: CV01-delivered ultrasound

• Registration Number: NCT05362409
• Lead Sponsor: Alpheus Medical, Inc.

Brief Summary

A Phase 1 Multi-center clinical Trial Evaluating the Safety and Tolerability of 5-aminolevulinic Acid (5-ALA) Combined With CV01 Delivery of Ultrasound for Sonodynamic Therapy (SDT) in Patients With recurrent High Grade Glioma (HGG).

Detailed Description

High-grade gliomas are the most commonly occurring primary CNS tumors in adults. The investigational product in this clinical study is a drug-device combination product consisting of 5-ALA HCl oral solution and the CV01 ultrasound delivery device. 5-ALA will be administered as a sonosensitizer prior to CV01-delivered ultrasound and will be re-administered every 4 weeks prior to CV01 ultrasound delivery. The CV01 device will deliver non-ablative, low-intensity ultrasound to deep regions of the brain to induce apoptosis of cancer cells. Part A will focus on duration escalation and determining the recommended duration of CV01 delivered ultrasound. Part B will further explore safety and tolerability through cohort expansion at the recommended duration of CV01 delivered ultrasound. Part C will include an exploratory surgical cohort at the recommended duration of CV01 delivered ultrasound. This FIH study will evaluate escalating durations of ultrasound delivery with CV01 and will enroll up to 48 patients.

Study Timeline

• Study First Submitted: 2022-05-02
• Study First Submitted QC: 2022-05-02
• Study First Posted: 2022-05-05
• Study Start: 2022-06-29
• Primary Completion: 2024-12-03
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-10
• Last Update Posted: 2025-01-13
• Study Completion: 2025-04-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

Not provided

Exclusion Criteria

1. Primary infratentorial or brainstem tumors

2. Primary spinal cord tumors

3. Bihemispheric disease (enhancing or non-enhancing) or tumors that involve the bilateral corpus callosum

4. Women who are pregnant or breastfeeding

5. Inability to undergo MRI or receive gadolinium (Gd)-based contrast agents

6. Hypersensitivity to 5-ALA or porphyrins

7. Average skull thickness at the treatment field > 10 mm as assessed by Alpheus Medical.

   The treatment field is defined as the various locations on the head where the transducer will be coupled to the patient. The average skull thickness at each treatment field will be determined by Alpheus Medical through post-processing the thin cut head computed tomography (CT) (without contrast). The patient's CT scan must be provided to Alpheus Medical for evaluation as part of the Screening and Enrollment process.

8. Hemorrhagic or ischemic stroke (including transient ischemic attacks) and central nervous system bleeding in the preceding 6 months that are not related to glioma surgery. History of prior intratumoral bleeding is not an exclusion criterion; however, patients with a history of prior intratumoral or intracranial bleeding will undergo a non-contrast head CT to exclude acute bleeding.

9. Patients who have clinically significant edema requiring urgent intervention (e.g., surgery, initiation of steroids, escalating doses of steroids).

10. Patients with progressive and rapid clinical deterioration that, in the opinion of the investigator, is likely to worsen during the first cycle of treatment or in the peri-operative interval (in the surgical cohort)

11. Cumulative prior RT dose > 64 Gy

12. Acute or chronic types of porphyria

13. Gastrointestinal disorder that negatively affects absorption

14. Known active hepatitis B or C (Note: testing is not required)

15. Known human immunodeficiency virus (HIV) infection (Note: testing is not required)

16. Unable to avoid phototoxic drugs (e.g., St. John's wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulfonamides, quinolones, and tetracyclines) for 24 hours prior to and following 5-ALA administration

17. Any other concurrent severe or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, cardiac disease, clinically significant psychiatric or neurological disorder, active or uncontrolled infection)

18. Patient has a condition the Investigator believes would interfere with the ability to provide informed consent or comply with study instructions, or that might confound the interpretation of the study results or put the patient at undue risk

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
5-ALA with CV01	5 Aminolevulinic Acid	5-aminolevulinic acid \[5-ALA\] with CV01-delivered ultrasound
5-ALA with CV01	CV01-delivered ultrasound	5-aminolevulinic acid \[5-ALA\] with CV01-delivered ultrasound

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events (Safety and Tolerability)	12 Months	Safety and tolerability as determined by the incidence of adverse events (AEs), including severe AEs and serious AEs (SAEs)
To determine the Maximum Tolerable Duration (MTDu)	12 Months	The MTDu is defined as the highest duration at which fewer than 1/3 of patients experience a Duration limited toxicity

Secondary Outcome Measures

Name	Time	Method
Assessment of Overall survival (OS)	12 Months
Assessment of Overall response rate (ORR)	12 Months	ORR assessed by RANO criteria
Assessment of Progression free survival (PFS)	12 Months
Assessment of Duration of Response (DoR)	12 Months

Trial Locations

Locations (3)

Washington University School of Medicine in St.Louis; 🇺🇸 Saint Louis, Missouri, United States

Dent Neurosciences Research Center; 🇺🇸 Amherst, New York, United States

Northwell; 🇺🇸 Lake Success, New York, United States