A Study of Sonodynamic Therapy Using SONALA-001 and Exablate 4000 Type 2.0 in Subjects With Recurrent GBM

NCT05370508 | Terminated Phase 1 DMC FDA Drug FDA Device

• 2 other identifiers: SDT-202R44CA275508
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 6

Brief Summary

The primary objectives of this trial are to evaluate the safety, dose-limiting toxicities, maximum tolerated dose (MTD), maximum administered dose (MAD) and recommended Phase 2 dose (RP2D) for future study after a single treatment of SONALA-001 in combination with MRgFUS and to evaluate preliminary efficacy of sonodynamic therapy (SDT) using SONALA-001 and Exablate Type 2.0 device in subjects with progressive or recurrent GBM.

Conditions

Recurrent GBM

Keywords

Sonodynamic Therapy; SONALA-001; Exablate 4000 Type 2.0; MR-guided Focused Ultrasound; SDT; rGBM; Aminolevulinic acid HCI; ALA HCI; ALA

Outcome Measures

Primary Outcomes (6)

• Safety and Tolerability of SONALA-001 SDT as assessed by the frequency and severity of dose-limiting toxicities (DLTs)

  Safety and tolerability of SONALA-001 SDT Definitions of Dose Limiting Toxicities (DLTs): The DLT window is the 21-day period following the first study treatment per patient. DLTs are defined as the following events during the DLT window, not clearly related to underlying disease, disease progression or intercurrent illness, as determined by safety review committee: Any death Non-hematologic toxicity: Any CTCAE Grade 3 or higher Hy's law cases Moderate heating/burning at the scalp Grade 3 or greater neurological toxicities Evidence of clinically significant tissue damage outside the region targeted by MRgFUS Grade 3 or greater photosensitivity in subjects strictly following restrictions to light exposure to sunlight or room lights for 48 hours after SONALA-001 administration Hematologic toxicity: Grade 4 neutropenia for more than 7 days Grade 3 or higher thrombocytopenia with clinically significant bleeding Neutropenic fever

  Day 1 to Day 21 post treatment

• Safety and Tolerability of SONALA-001 SDT as assessed by the number of subjects with Adverse Events (AEs), adverse device effects (ADEs), serious AEs (SAEs) and serious device effects (SADEs)

  Safety and tolerability of SONALA-001 SDT Definition of Adverse Event (AE) An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after the first dose of investigational drug. Abnormal laboratory values or test results occurring after the first dose of investigational drug constitute AEs only if they induce clinical signs or symptoms, are considered clinically significant, require therapy (e.g., hematologic abnormality that requires transfusion or hematological stem cell support) except electrolytes which require replacement therapy and correct to CTCAE grade ≤ 1 within 48 hours unless considered life-threatening, or require changes in study medication(s).

  Day 1 to 12 months

• Safety and Tolerability of SONALA-001 SDT as assessed by the number of subjects with abnormal hematology, chemistry, coagulation and urinalysis laboratory tests.

  Lab tests covered by CTCAE version 5.0 or most current will be graded accordingly. For lab tests covered by CTCAE, a Grade 0 will be assigned for all non-missing values not graded as 1 or higher. Grade 5 will not be used. For lab tests where grades are not defined by CTCAE, results will be categorized by low/normal/high classifications based on lab normal ranges or categorized by normal/abnormal for character (descriptive) lab values.

  Day 1 to 12 months

• To determine Maximum Administered Dose (MAD), Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) after a single treatment of MR-guided Focused Ultrasound (MRgFUS) energy in combination with SONALA-001 SDT (Phase 1)

  Determination of Recommended Phase 2 Dose of SONALA-001 SDT in combination with MRgFUS

  Up to 3 weeks post treatment

• Progression-free survival rate at 6 Months (Phase 2)

  To evaluate preliminary efficacy (PFS rate at 6 months) of the RP2D of ALA SDT treatments by mRANO in subjects with recurrent GBM

  6 Months

• Safety of the RP2D of ALA SDT as assessed by the number of subjects with AEs/ADEs, SAEs/SADEs, abnormal laboratory tests, neurologic and physical examinations, vital signs, and ECGs.

  Safety of the RP2D of ALA SDT

  Day 1 to 12 months

Secondary Outcomes (15)

• To evaluate the pharmacokinetics (PK) of ALA and Protoporphyrin IX (PpIX) following intravenous (IV) dosing with SONALA-001 by calculating Area Under the plasma Concentration (AUC) vs. time from time 0 to the last measurable time point (AUC-t) (Phase 1)

  Day 1 to 24 hours post SONALA-001 dosing

• To evaluate the pharmacokinetics (PK) of ALA and Protoporphyrin IX (PpIX) following intravenous (IV) dosing with SONALA-001 by calculating AUC for plasma concentration vs. time from time 0 to infinity (AUC0-∞) (Phase 1)

  Day 1 to 24 hours post SONALA-001 dosing

• To evaluate the pharmacokinetics (PK) of ALA and Protoporphyrin IX (PpIX) following intravenous (IV) dosing with SONALA-001 by calculating AUC for plasma concentration vs. time from time 0 to time to maximum drug concentration (Tmax) (Phase 1)

  Day 1 to 24 hours post SONALA-001 dosing

• To evaluate the pharmacokinetics (PK) of ALA and Protoporphyrin IX (PpIX) following intravenous (IV) dosing with SONALA-001 by calculating AUC for plasma concentration vs. time from time 0 to time to terminal elimination half-life (t½) (Phase 1)

  Day 1 to 24 hours post SONALA-001 dosing

• To evaluate the pharmacokinetics (PK) of ALA and Protoporphyrin IX (PpIX) following intravenous (IV) dosing with SONALA-001 by calculating AUC for plasma concentration vs. time from time 0 to time to clearance. (Phase 1)

  Day 1 to 24 hours post SONALA-001 dosing

Study Arms (5)

Cohort 1

EXPERIMENTAL

10 mg/kg IV SONALA-001 (ALA) and MR-guided Focused Ultrasound (MRgFUS) Energy Level 1

Combination Product: SONALA-001 (ALA) and MR-Guided Focused Ultrasound device (MRgFUS)

Cohort 2

EXPERIMENTAL

10 mg/kg IV SONALA-001 (ALA) and MR-guided Focused Ultrasound (MRgFUS) Energy Level 2

Combination Product: SONALA-001 (ALA) and MR-Guided Focused Ultrasound device (MRgFUS)

Cohort 3

EXPERIMENTAL

10 mg/kg IV SONALA-001 (ALA) and MR-guided Focused Ultrasound (MRgFUS) Energy Level 3

Combination Product: SONALA-001 (ALA) and MR-Guided Focused Ultrasound device (MRgFUS)

Cohort 4

EXPERIMENTAL

10 mg/kg IV SONALA-001 (ALA) and MR-guided Focused Ultrasound (MRgFUS) Energy Level 4

Combination Product: SONALA-001 (ALA) and MR-Guided Focused Ultrasound device (MRgFUS)

Cohort 5

EXPERIMENTAL

Recommended Phase 2 Dose (RP2D) IV SONALA-001 (ALA) and MR-guided Focused Ultrasound (MRgFUS) Energy Level 5

Combination Product: SONALA-001 (ALA) and MR-Guided Focused Ultrasound device (MRgFUS)

Interventions

SONALA-001 (ALA) and MR-Guided Focused Ultrasound device (MRgFUS) COMBINATION_PRODUCT

SONALA-001(ALA) given 6-12 hours prior to receiving the MRgFUS

Also known as: Exablate Type 2.0

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Eligibility Criteria

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

You may qualify if:

• Must be 18 years or older at the screening visit.
• Histologically proven GBM (as defined in 2021 WHO Classification of Tumors of the Central Nervous System; Louis, Perry, et al. 2021) that has recurred or progressed, and for which resection is not indicated.
• Tumor must be located in the supratentorial or cerebellar region. Tumors with infratentorial locations require consultation with the Sponsor/Medical Monitor to confirm suitability for treatment.
• Previous treatment with standard of care radiotherapy (RT) and temozolomide (temozolomide required only if tumor has at least partial methylation of the O6-methylguanine-DNA methyltransferase promoter). Temozolomide should be administered concurrent with RT and adjuvantly for newly diagnosed disease unless intolerant or ineligible for treatment.
• No recurrence within 4 weeks of completion of RT, defined from the imaging assessment immediately after completion of RT.
• Up to two prior systemic treatments for recurrent or progressing disease.
• If receiving corticosteroids, must be maintained on a stable or decreasing dosage of steroids for at least 7 days prior to C1D1.
• Karnofsky Performance Score (KPS) ≥ 70 assessed within 14 days of C1D1.
• Must have adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1.5 ×10⁹/L (1,500/μL), without the use of myeloid growth factors (e.g., granulocyte-colony stimulating factor) within 7 days prior to C1D1 for short acting growth factors and 14 days for long-acting growth factors to meet eligibility.
• Platelets ≥ 75 × 10⁹/L (100,000/μL), unsupported, defined as no platelet transfusion within 7 days prior to C1D1.
• Hemoglobin ≥ 9 g/dL maintained without the need for erythropoietin stimulating agents; subjects that require transfusion or growth factors need to demonstrate stable hemoglobin of ≥ 9 g/dL over at least a 7-day period immediately prior to C1D1.
• Total bilirubin ≤ 1.5 times institutional upper limit of normal (ULN), in subjects with Gilbert syndrome, total bilirubin \>1.5 ULN as long as direct bilirubin is normal.
• ALT (SGPT) \< 3 x institutional ULN.
• AST (SGOT) \< 3 x institutional ULN.

You may not qualify if:

• Target disease
• Tumor in the brainstem (not including fluid-attenuated inversion recover \[FLAIR\] changes), or a diagnosis of gliomatosis cerebri (highly infiltrative T2 hyperintense tumor with ill-defined margins encompassing at least three lobes of the brain). Tumors with infratentorial locations require consultation with the Sponsor/Medical Monitor to confirm suitability for treatment.
• Concurrent or prior therapy
• Subjects who have not recovered to Grade 1 or baseline from AEs (CTCAE v 5.0, or most current) related to prior anticancer therapy (excluding alopecia, lymphopenia, peripheral neuropathy, and ototoxicity, which are excluded only if ≥ Grade 3).
• Prior systemic anticancer treatment:
• Chemotherapy, biologic therapy (i.e., small molecular inhibitors), monoclonal antibodies, investigational agents) within 21 days or 5 half-lives (whichever is shorter), prior to C1D1 or per below:
• Nitrosoureas or bevacizumab within 2 weeks prior to C1D1
• If a subject is receiving an anti-PD-1 or anti-PD-L1 antibody on a shorter frequency (i.e., every two weeks), then the subject is eligible if last dose was within 2 weeks prior to C1D1.
• Prior therapy such as interstitial brachytherapy, Gliadel® Wafers (carmustine implants), laser interstitial thermal therapy (LITT), or Optune therapy, within 4 weeks prior to C1D1 or as long as there are any ongoing treatment-related CTCAE Grade ≥2 AEs or intolerable side effects.
• Radiation therapy within 4 weeks prior to C1D1.
• Use of potentially phototoxic substances (e.g., St. John's wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, tetracyclines, sulfonamides, quinolones, hypericin extracts, topical preparations containing ALA) within 24 hours before and after SONALA-001 infusion.
• Use of fish oil supplements within 24 hours of C1D1 is allowed if the subject's clotting parameters fall within normal limits.
• Use of blood thinning agents within 7 days prior to C1D1. Subjects whose medical condition does not permit discontinuation of this therapy are excluded.
• Prior major surgery within 3 weeks prior to C1D1. Major surgery is defined as any significantly invasive procedure into a major body cavity (abdomen, cranium etc.) and/or surgery requiring extensive recuperation (joint replacement). Please discuss with the Sponsor/Medical Monitor if there are any questions.
• Medical history and concurrent disease

Sponsors & Collaborators

• SonALAsense, Inc.: lead

Study Sites (6)

Ivy Brain Tumor Center

Phoenix, Arizona, 85013, United States

Location

UCSF

San Francisco, California, 94143, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Corina Andresen, MD

  SonALAsense, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2022
• First Posted: May 11, 2022
• Study Start: February 6, 2023
• Primary Completion: June 11, 2024
• Study Completion: July 8, 2024
• Last Updated: July 26, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)