Study of Sonodynamic Therapy Using SONALA-001 and Exablate 4000 Type 2 in Recurrent GBM

• ClinicalTrials.gov Identifier: NCT05370508
• Recruitment Status: Recruiting
• First Posted: May 11, 2022
• Last Update Posted: February 8, 2023
• Sponsor: SonALAsense, Inc.
• Information provided by (Responsible Party): SonALAsense, Inc.

Study Description

Brief Summary:

The primary objectives of this trial are to evaluate the safety, dose-limiting toxicities, recommended Phase 2 schedule, and preliminary efficacy of sonodynamic therapy (SDT) using SONALA-001 and Exablate Type-2 device in subjects with recurrent or progressive GBM.

Condition or disease	Intervention/treatment	Phase
Recurrent GBM	Combination Product: SONALA-001 (ALA) and Exablate device	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Dose Escalation and Expansion Study of Sonodynamic Therapy With SONALA-001 in Combination With Exablate 4000 Type-2 MR-guided Focused Ultrasound in Patients With Recurrent or Progressive Glioblastoma Multiforme
• Estimated Study Start Date: February 28, 2023
• Estimated Primary Completion Date: April 2026
• Estimated Study Completion Date: May 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1; Dose level 1 of SONALA-001 (ALA) and Dose level 1 of Exablate device	Combination Product: SONALA-001 (ALA) and Exablate device; SONALA-001(ALA) given prior to receiving MRgFUS via the Exablate device.; Other Name: Exablate Type-2
Experimental: Cohort 2; Does level 2 of SONALA-001 (ALA) Dose level 2 of Exablate device	Combination Product: SONALA-001 (ALA) and Exablate device; SONALA-001(ALA) given prior to receiving MRgFUS via the Exablate device.; Other Name: Exablate Type-2
Experimental: Cohort 3; Dose level 3 of SONALA-001 (ALA) and Dose level 3 of Exablate device	Combination Product: SONALA-001 (ALA) and Exablate device; SONALA-001(ALA) given prior to receiving MRgFUS via the Exablate device.; Other Name: Exablate Type-2
Experimental: Cohort 4; Dose level 4 of SONALA-001 (ALA) and Dose level 4 of Exablate device	Combination Product: SONALA-001 (ALA) and Exablate device; SONALA-001(ALA) given prior to receiving MRgFUS via the Exablate device.; Other Name: Exablate Type-2
Experimental: Cohort 5; Dose level 5 of SONALA-001 (ALA) and Dose level 5 of Exablate device	Combination Product: SONALA-001 (ALA) and Exablate device; SONALA-001(ALA) given prior to receiving MRgFUS via the Exablate device.; Other Name: Exablate Type-2
Experimental: Cohort 6; Dose level 6 of SONALA-001 (ALA) and Dose level 6 of Exablate device	Combination Product: SONALA-001 (ALA) and Exablate device; SONALA-001(ALA) given prior to receiving MRgFUS via the Exablate device.; Other Name: Exablate Type-2
Experimental: Cohort 7; 2 treatments of SONALA-001 (ALA) and Exablate device	Combination Product: SONALA-001 (ALA) and Exablate device; SONALA-001(ALA) given prior to receiving MRgFUS via the Exablate device.; Other Name: Exablate Type-2
Experimental: Cohort 8; 3 treatments of SONALA-001 (ALA) and Exablate device at the Recommended Phase 2 Dose (RP2D)	Combination Product: SONALA-001 (ALA) and Exablate device; SONALA-001(ALA) given prior to receiving MRgFUS via the Exablate device.; Other Name: Exablate Type-2
Experimental: Cohort 9; Expansion to approximately 30 patients at the Recommended Phase 2 Dose (RP2D) and the Recommended Phase 2 Schedule (RP2S) of SONALA-001 (ALA) and Exablate device	Combination Product: SONALA-001 (ALA) and Exablate device; SONALA-001(ALA) given prior to receiving MRgFUS via the Exablate device.; Other Name: Exablate Type-2

Outcome Measures

Primary Outcome Measures :

1. Safety of ALA SDT [ Time Frame: Day 1 to 12 months ]
   Tabulation of treatment-emergent adverse events
2. MTD [ Time Frame: Day 1 to Day 29 ]
   Frequency of DLTs in each Cohort
3. Determination of Recommended Phase 2 Schedule [ Time Frame: Day 1 to Day 29 after the final treatment in each Cohort ]
   Frequency of DLTs in each Cohort
4. Progression-free survival rate at 6 Months (Expansion Cohort only) [ Time Frame: 6 Months ]
   Percentage of patients without progression or death at 6 Months post treatment

Secondary Outcome Measures :

1. Area under the plasma concentration vs time from Time 0 to the last measurable timepoint (AUC0-t) of ALA in blood plasma [ Time Frame: Day 1 to 24 hours post SONALA-001 dosing ]
   Samples will be collected at 10 time points during 24 hours pre/post SONALA-001 administration
2. Area under the plasma concentration vs time from Time 0 to infinity (AUC0-∞) of ALA in blood plasma [ Time Frame: Day 1 to 24 hours post SONALA-001 dosing ]
   Samples will be collected at 10 time points during 24 hours pre/post SONALA-001 administration
3. Terminal elimination half-life (t1/2) of ALA in blood plasma [ Time Frame: Day 1 to 24 hours post SONALA-001 dosing ]
   Samples will be collected at 10 time points during 24 hours pre/post SONALA-001 administration
4. Elimination rate constant of ALA in blood plasma [ Time Frame: Day 1 to 24 hours post SONALA-001 dosing ]
   Samples will be collected at 10 time points during 24 hours pre/post SONALA-001 administration
5. Clearance of ALA in blood plasma [ Time Frame: Day 1 to 24 hours post SONALA-001 dosing ]
   Samples will be collected at 10 time points during 24 hours pre/post SONALA-001 administration
6. Time to maximum drug concentration (Tmax) of ALA in blood plasma [ Time Frame: Day 1 to 24 hours post SONALA-001 dosing ]
   Samples will be collected at 10 time points during 24 hours pre/post SONALA-001 administration
7. Area under the plasma concentration vs time from Time 0 to the last measurable timepoint (AUC0-t) of PpIX in blood plasma [ Time Frame: Day 1 to 24 hours post SONALA-001 dosing ]
   Samples will be collected at 10 time points during 24 hours pre/post SONALA-001 administration
8. Area under the plasma concentration vs time from Time 0 to infinity (AUC0-∞) of PpIX in blood plasma [ Time Frame: Day 1 to 24 hours post SONALA-001 dosing ]
   Samples will be collected at 10 time points during 24 hours pre/post SONALA-001 administration
9. Terminal elimination half-life (t1/2) of PpIX in blood plasma [ Time Frame: Day 1 to 24 hours post SONALA-001 dosing ]
   Samples will be collected at 10 time points during 24 hours pre/post SONALA-001 administration
10. Elimination rate constant of PpIX in blood plasma [ Time Frame: Day 1 to 24 hours post SONALA-001 dosing ]
    Samples will be collected at 10 time points during 24 hours pre/post SONALA-001 administration
11. Clearance of PpIX in blood plasma [ Time Frame: Day 1 to 24 hours post SONALA-001 dosing ]
    Samples will be collected at 10 time points during 24 hours pre/post SONALA-001 administration
12. Time to maximum drug concentration (Tmax) of PpIX in blood plasma [ Time Frame: Day 1 to 24 hours post SONALA-001 dosing ]
    Samples will be collected at 10 time points during 24 hours pre/post SONALA-001 administration
13. Volume of distribution as steady state (Vss) [ Time Frame: Day 1 to 24 hours post SONALA-001 dosing ]
    Samples will be collected at 10 time points during 24 hours pre/post SONALA-001
14. Objective Response (mRANO) [ Time Frame: Day 0 to 12 months ]
    Percentage of patients with a best overall response (BOR) of complete response of CR or PR
15. Duration of response [ Time Frame: Day 1 to 12 months ]
    Time from date of first documented CR or PR until progression or death due to any cause.
16. Clinical benefit rate (CBR: CR, PR, and SD) [ Time Frame: Day 1 to 12 months ]
    Clinical benefit rate (CBR) defined as the proportion of patients with a BOR of CR or PR or SD
17. Duration of clinical benefit [ Time Frame: Day 1 to 12 months ]
    Time from date of first documented CR, PR, or SD until progression or death due to any cause.
18. Progression-free survival [ Time Frame: Day 1 to 12 months ]
    Time from first dose of SONALA-001 to progression or death due to any cause.
19. Overall survival [ Time Frame: Day 1 to 12 months ]
    Time from first dose of SONALA-001 to death due to any cause.
20. Time to response (TTR) [ Time Frame: Day 1 to 12 months ]
    Time from first dose of SONALA-001 to the first documented response, CR or PR
21. Progression-free survival rate at 6 Months (Dose escalation only) [ Time Frame: 6 Months ]
    Percentage of patients without progression or death at 6 Months post treatment
22. Progression-free survival rate at 12 Months [ Time Frame: 12 Months ]
    Percentage of patients without progression or death at 12 Months post treatment

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Must be 18 years or older at screening visit.
2. Histologically proven, primary (de novo) GBM, 2021 WHO Classification of Tumors of the Central Nervous System, (Louis et al. 2021) that has recurred or progressed (first or second recurrence, including this recurrence) and resection not indicated.
3. A single recurrent or progressing tumor that must be supratentorial, contrast-enhancing, and bi-dimensionally measurable that is 5 mL to 30 mL in volume, based on MRI within 14 days prior to Day 1.
4. Previous first-line treatment with at least standard-of-care radiotherapy and temozolomide (temozolomide required only if tumor has at least partial methylation of the O6-methylguanine-DNA methyltransferase promoter [MGMTp]). Temozolomide should be administered concurrent with RT and adjuvantly for newly diagnosed disease unless intolerant or ineligible for treatment.
5. No recurrence within 12 weeks of completion of radiotherapy, defined from the imaging assessment immediately after completion or radiotherapy.
6. Up to one prior systemic treatment for recurrent or progressing disease.
7. If receiving corticosteroids, must be maintained on a stable or decreasing dosage of steroids for 7 days prior to the baseline MRI scan.
8. If receiving corticosteroids, must be maintained on a stable or decreasing dosage of steroids for at least 7 days prior to Day 1.
9. Karnofsky Performance Score (KPS) > 70.

10. Must have adequate organ and marrow function as defined below:

    • Absolute neutrophil count ≥ 1.5 × 109/L (1,500/μL), without the use of G-CSF within 7 days prior to Day 1 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 Day 1
    • Hemoglobin ≥ 9 g/dL, patients 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 Day 1
    • Total bilirubin ≤ 1.5 times institutional upper limit of normal (ULN), in patients with Gilbert syndrome, total bilirubin >1.5 ULN as long as direct bilirubin is normal
    • ALT (SGPT) < 3 x institutional upper limit of normal
    • AST (SGOT) < 3 x institutional upper limit of normal
    • Albumin ≥ 3 g/dl
    • Potassium ≥ LLN
    • Serum total calcium (correct for serum albumin) or ionized calcium ≥ LLN
    • Estimated creatinine clearance (CrCl) by the Cockcroft-Gault (C-G) equation or measured ≥ 60 mL/min. Actual body weight will be used for calculation of the Cockcroft-Gault equation. If estimated CrCl is abnormal, accurate measurement should be obtained by 24-hour urine collection to measure creatinine clearance.
11. All colony-forming growth factor(s) (i.e., filgrastim, sargramostim or erythropoietin) must have been discontinued for at least 7 days prior to Day 1 or 14 days if PEG formulations were received.
12. Have a life expectancy of at least 12 weeks.
13. An understanding, ability, and willingness to fully comply with study procedures and restrictions.
14. Ability to provide written, signed, and dated (personally or via a legally authorized representative) informed consent at screening as applicable to participate in the study.
15. Females of childbearing potential (FOCP) must have a negative serum at screening. Patients of childbearing or child fathering potential must be willing to use highly effective birth control during the entire study. Acceptable forms of birth control include hormonal contraceptives (oral, injectable, transdermal, or intravaginal) or intrauterine device (IUD) for at least one week prior to study treatment, condom and spermicidal or diaphragm and spermicidal. Other acceptable forms of birth control include a) abstinence for patients who are not sexually active or b) if the subject is in a monogamous relationship with a partner who is sterile (e.g., vasectomy performed at least 6 months prior to subject's first study treatment). Patients who become sexually active or begin to have relations with a partner who is not sterile during the trial must agree to use an effective form of birth control for the duration of the study. FOCP taking hormonal therapy must be on treatment for at least 12 weeks prior to Cycle 1 Day 1 and must not change their dosing regimen during the study

Exclusion criteria:

Patients eligible for this study must not meet any of the following criteria:

1. Secondary glioblastoma with IDH1 mutations (i.e., glioblastoma that progressed from low-grade diffuse astrocytoma or AA).
2. Tumor in the brainstem (not including fluid-attenuated inversion recover [FLAIR] changes), an infratentorial tumor, diagnosis of gliomatosis cerebri (highly infiltrative T2 hyperintense tumor with ill-defined margins encompassing at least three lobes of the brain.
3. Prior surgical resection for recurrent or progressed GBM.
4. Patients who have not recovered to grade 1 or baseline from adverse events (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.

5. Prior systemic anticancer treatment (i.e., chemotherapy, biologic therapy [i.e., small molecular inhibitors], monoclonal antibodies, investigational agents]) within 21 days or 5 half-lives, whichever is shorter, prior to Day 1 or per below:

   • Temozolomide (low-dose, continuous administration) within 28 days prior to Day 1
   • Nitrosoureas within 6 weeks prior to Day 1
   • 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 within 2 weeks prior to Day 1
   • Bevacizumab within 2 weeks prior to Day 1
6. Prior therapy that included interstitial brachytherapy or Gliadel® Wafers (carmustine implants) for newly diagnosed GBM within 12 weeks prior to Day 1. Patients treated with interstitial brachytherapy or Gliadel® Wafers at first recurrence are excluded.
7. Optune therapy for newly diagnosed GBM within 3 weeks prior to Day 1. Patients treated with Optune therapy at first recurrence are excluded.
8. Radiation therapy within 12 weeks prior to Day 1.
9. 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.
10. Use of herbal and fish oil supplements within 7 days prior to Day 1.
11. Use of blood thinning agents within 7 days prior to Day 1.

12. Prior major surgery within 3 weeks prior to Day 1. 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 Medical Monitor if there are any questions.

    Medical history and concurrent disease

13. An Overall Skull Density Ratio of 0.45 (±0.05) or less as calculated from the screening non-contrast CT.
14. Diagnosis of porphyria.
15. Hypersensitivity against porphyrins.
16. Known history of allergy to gadolinium contrast agents.
17. Inability to undergo MRI (e.g., presence of a pacemaker).
18. Malignant disease, other than that being treated in this study. Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. Other exceptions include malignancies that were treated curatively and have not recurred within 2 years prior to Day 1 and any malignancy considered indolent and has never required therapy.
19. Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
20. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required.
21. Significant acute deterioration in neurologic status within 7 days prior to Day 1, in the opinion of the investigator including but not limited to new onset seizures and/or increasing doses of corticosteroids.

22. Uncontrolled concurrent illness including, but not limited to:

    • ongoing or active infection
    • transfusion dependent thrombocytopenia or anemia that prevent meeting hematological inclusion criteria
    • psychiatric illness/social situations that would limit compliance with study requirements

23. Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:

    • Symptomatic congestive heart failure
    • Unstable angina pectoris or cardiac arrhythmia
    • Baseline QTcF (Fridericia) ≥ 470 milliseconds
    • Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome
24. Pregnancy or breastfeeding.
25. A known or underlying medical condition that, in the opinion of the investigator or Sponsor, could make the administration of study drug/treatment hazardous to the patient, or could adversely affect the ability of the patient to comply with or tolerate the study.
26. Inability to participate in the opinion of the investigator, by being unwilling or unable to return for required follow-up visits or to obtain follow-up studies to assess toxicity to therapy or to adhere to study plan, procedures, and restrictions.

Contacts and Locations

Contacts

Contact: OOO; 510-831-2220; info@sonalasense.com

Locations

United States, Arizona

Ivy Brain Tumor Center; Recruiting

Phoenix, Arizona, United States, 85013

Contact: Phase 0 Navigator 602-406-8605 Research@ivybraintumorcenter.org

Principal Investigator: Nader Sanai, MD

United States, New York

NYU Langone Health; Recruiting

New York, New York, United States, 10016

Contact: David Hargrove 646-501-0368 David.Hargrove@nyulangone.org

Principal Investigator: Dimitris Placantonakis, MD, PhD

United States, Ohio

Cleveland Clinic; Recruiting

Cleveland, Ohio, United States, 44195

Contact: Rachel Hufsey hufseyr@ccf.org

Principal Investigator: Matthew Grabowski, MD

United States, Texas

MD Anderson Cancer Center; Not yet recruiting

Houston, Texas, United States, 77030

Contact: Summer Stovall 713-745-4243 SStovall@mdanderson.org

Principal Investigator: Jeffrey Weinberg, MD

Sponsors and Collaborators

SonALAsense, Inc.

Investigators

• Principal Investigator: Stuart Marcus, MD, PhD; SonALAsense, Inc.

More Information

• Responsible Party: SonALAsense, Inc.
• ClinicalTrials.gov Identifier: NCT05370508
• Other Study ID Numbers: SDT-202
• First Posted: May 11, 2022
• Last Update Posted: February 8, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Additional relevant MeSH terms:

Recurrence; Disease Attributes; Pathologic Processes