A Phase 2 Study of Sonodynamic Therapy Using SONALA-001 and Exablate 4000 Type 2.0 in Patients with DIPG

NCT05123534 | Suspended Phase 2 DMC FDA Drug FDA Device

• 3 other identifiers: SDT-201FD-R-7538R44CA261516
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

Brief Summary

The primary objectives of this trial are to evaluate the safety and tolerability of sonodynamic therapy (SDT) using SONALA-001 and Exablate Type 2.0 device and to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of MR-Guided Focused Ultrasound (MRgFUS) energy in combination with SONALA-001 in subjects with diffuse intrinsic pontine glioma Funding Source - FDA OOPD

Conditions

Diffuse Intrinsic Pontine Glioma; Diffuse Midline Glioma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• To evaluate the safety and tolerability of SDT in DIPG subjects to generate data that will aid in the design of a larger Phase 2b trial.

  Safety and tolerability as assessed by the frequency and severity of dose-limiting toxicities (DLTs), AEs, laboratory and ECG tests, vital signs, weight, physical and neurological exams.

  Day 1 (SDT Study Treatment Day) to 12 months post-treatment

• To determine the Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) of MR-Guided Focused Ultrasound (MRgFUS) energy in combination with SONALA-001 (SDT) in subjects with DIPG.

  MTD and RP2D (determined in consultation with the Safety Review Committee \[SRC\]): The Bayesian Optimal Interval (BOIN) (SONALA-001 and MRgFUS) method will be employed to derive an MTD for the combination drug and device and estimate RP2D. "R Package for Designing Single-Agent and Drug-Combination Dose-Finding Trials Using Bayesian Optimal Interval Designs" will be implemented.

  Up to 3 weeks post-treatment

Secondary Outcomes (6)

• Preliminary efficacy, including objective response rate (ORR); Response Assessment in Pediatric Neuro-Oncology (RAPNO); Modified Response Assessment in Neuro-Oncology (mRANO).

  Day 1 to 12 months

• Progression-free survival (PFS)

  Day 1 to 12 months

• Duration of response (DOR)

  Day 1 to 12 months

• Overall survival (OS)

  Day 1 to 24 months

• To evaluate the pharmacokinetics (PK) of ALA and Protoporphyrin IX (PpIX) following intravenous (IV) dosing with SONALA-001.

  Day 1 to 24 hours post SONALA-001 dosing

Other Outcomes (5)

• To evaluate the safety and tolerability of SDT in the DMG subjects

  Day 1 (SDT Study Treatment Day) to 12 months post-treatment

• To evaluate the objective response rate (ORR) in the DMG subjects.

  Day 1 to 12 months

• Progression-free survival (PFS) in the DMG subjects.

  Day 1 to 12 months

Study Arms (5)

Cohort 1

EXPERIMENTAL

5 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

5 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 - DIPG Cohort at RP2D

EXPERIMENTAL

The RP2D of SONALA-001 (ALA) and MR-guided Focused Ultrasound (MRgFUS) Energy

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

Cohort 5 - DMG Cohort at RP2D

EXPERIMENTAL

The RP2D of SONALA-001 (ALA) and MR-guided Focused Ultrasound (MRgFUS) Energy

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 - DIPG Cohort at RP2D; Cohort 5 - DMG Cohort at RP2D

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• DIPG Subjects:
• Newly diagnosed, radiographically typical DIPG, defined as a tumor with a pontine epicenter and diffuse involvement of more than ⅔ of the pons and without evidence of dissemination, are eligible with or without histologic confirmation.
• The diagnosis imaging scan must be reviewed by the study site's neuroradiologist and the principal investigator. The diagnosis imaging scan must subsequently be sent to the study central imaging vendor.
• Subjects who present with DIPG and dissemination at diagnosis, but after completion of radiotherapy have no dissemination on neuroimaging at screening, are considered eligible.
• Subjects with pontine lesions that do not meet radiographic criteria will be eligible if there is histologic confirmation of DIPG.
• Subjects may be asked to agree to provide access to previously obtained biopsy results.
• If tumor status is unknown or archival tumor tissue is not available, subjects may be asked to agree to submit a post-mortem biopsy specimen to enable molecular profiling of tumor.
• Prior treatment consisting of a minimum of 54 Gy standard focal radiotherapy administered over 42-49 days.
• Must be ≥ 4 weeks and ≤ 24 weeks post radiotherapy and must have recovered from acute effects to CTCAE (version 5) Grade 1 or baseline prior to Day 1.
• Must have stable to improved imaging by RAPNO (subjects ≤ 21 years of age) and mRANO (subjects \> 21 years of age) criteria comparing the scan obtained post radiotherapy to the scan obtained during the screening period. The comparison of diagnosis imaging scan and screening imaging scan must be reviewed by the study site's neuroradiologist and the principal investigator. If subjects present within 3 months after completion of radiotherapy and the comparison of the diagnosis scan to the screening scan is consistent with RAPNO/mRANO progression but pseudoprogression is a consideration, then the subject can be re-screened if the subject falls out of the screening window.
• Subjects who are on steroids must be on a stable to decreasing dose of steroids (maximum dexamethasone of 1 mg/m2/day) prior to Day 1.
• Minimum of 5 years of age. Subjects younger than 5 years old may be eligible after discussion with the Sponsor Medical Monitor/designee.
• A minimum head circumference of 52 cm as measured by physical exam. Subjects with a minimum head circumference smaller than 52 cm may be eligible after discussion with the Sponsor Medical Monitor/designee.
• Females of childbearing potential (FOCP) must have a negative serum or urine pregnancy test at screening. Subjects 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 ALA SDT, condom and spermicidal or diaphragm and spermicidal. Other acceptable forms of birth control include a) abstinence for subjects 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 ALA SDT treatment). Subjects 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 study entry and must not change their dosing regimen during the study.
• Ability to provide written, signed, and dated (personally or via a legally authorized representative) informed consent/and assent at screening as applicable to participate in the study.

You may not qualify if:

• DIPG Subjects:
• Evidence of progressive disease by radiologic criteria (RAPNO for subjects ≤ 21 years of age or mRANO for subjects \> 21 years of age).
• Increasing steroid dose prior to Day 1.
• Diagnosis of porphyria.
• Hypersensitivity against porphyrins.
• Current malignancies or relevant history of other malignancy, physical, or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures.
• Known history of human immunodeficiency virus (HIV), hepatitis B or C infection, or any active systemic infection.
• 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 Day 1 is allowed if the subject's clotting parameters fall within normal limits.
• Use of blood thinning agents within 7 days prior to Day 1. Subjects whose medical condition does not permit discontinuation of this therapy are excluded.
• Significant acute deterioration in neurologic status within 7 days prior to Day 1, in the opinion of the investigator.
• Inability to undergo MRI (e.g., presence of a pacemaker).
• Pregnancy or breastfeeding.
• Inability to return to study site for required study treatment and follow-up visits (i.e., due to residing or traveling outside of the United States). This includes inability to have local follow-up visits as allowed and outlined per protocol.
• Metal devices including but not limited to implanted devices in the brain or skull (e.g., shunts, catheters, drains, implants, clips, or other metallic implanted objects) are not allowed. NOTE: Ommaya Reservoirs, VP shunts (non-metallic) or similar are allowed.

Sponsors & Collaborators

• SonALAsense, Inc.: lead

Study Sites (3)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Children's National / Children's Research Institute

Washington D.C., District of Columbia, 20010-2916, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Corina Andresen, MD

  SonALAsense, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Drug/energy dose escalation to identify the RP2D as guided by BOIN for the combination of SONALA-001 and Exablate 4000 Type 2.0 MRgFUS. The primary focus of the proposed study is safety, tolerability and determination of the MTD and RP2D; therefore, statistical modeling and inferential statistics are not planned.

Study Record Dates

• First Submitted: October 11, 2021
• First Posted: November 17, 2021
• Study Start: August 12, 2022
• Primary Completion: July 30, 2024
• Study Completion: October 30, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)