Study of Safety and Pharmacokinetic Properties of Oral OKN-007 in Patients with Recurrent High-Grade Glioma

NCT05561374 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: OKN-007-OL-RMG-101
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 4

Brief Summary

This is a phase 1 open-label, multicenter study to investigate tolerability, safety and PK properties of oral OKN-007 in patients with recurrent high-grade glioma.

Conditions

High-grade Glioma; Oligodendroglioma; Astrocytoma; Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (5)

• Safety and tolerability: Adverse events

  Safety and tolerability will be evaluated from adverse events as reported according to CTCAE version 5.0.

  From Day 1 to 30 days after the last treatment

• Pharmacokinetic profile: Maximum plasma concentration (Cmax)

  Maximum plasma concentration (Cmax) will be calculated using the actual sample collection times.

  Pre-dose, 2 hours, 4 hours, 5 hours, 6 hours, and 8 hours post-dose on Days 1 in Cycle 1 and 2; 5 hours post-dose on Day 5; Pre-dose, 5 hours post-dose on Day 8 in Cycle 1; Pre-dose on Days 1 of Cycle 3 and 4 (each cycle is 28 days)

• Pharmacokinetic profile: Time to Cmax (Tmax)

  Time to Cmax (Tmax) will be calculated using the actual sample collection times.

  Pre-dose, 2 hours, 4 hours, 5 hours, 6 hours, and 8 hours post-dose on Days 1 in Cycle 1 and 2; 5 hours post-dose on Day 5; Pre-dose, 5 hours post-dose on Day 8 in Cycle 1; Pre-dose on Days 1 of Cycle 3 and 4 (each cycle is 28 days)

• Pharmacokinetic profile: Area under the curve (AUC)

  Area under the curve (AUC) will be calculated using the actual sample collection times.

  Pre-dose, 2 hours, 4 hours, 5 hours, 6 hours, and 8 hours post-dose on Days 1 in Cycle 1 and 2; 5 hours post-dose on Day 5; Pre-dose, 5 hours post-dose on Day 8 in Cycle 1; Pre-dose on Days 1 of Cycle 3 and 4 (each cycle is 28 days)

• Pharmacokinetic profile: Half-life time (t1/2)

  Half-life time (t1/2) will be calculated using the actual sample collection times.

  Pre-dose, 2 hours, 4 hours, 5 hours, 6 hours, and 8 hours post-dose on Days 1 in Cycle 1 and 2; 5 hours post-dose on Day 5; Pre-dose, 5 hours post-dose on Day 8 in Cycle 1; Pre-dose on Days 1 of Cycle 3 and 4 (each cycle is 28 days)

Study Arms (4)

Low-dose OKN-007, two times a day (BID)

EXPERIMENTAL

Dose Escalation Cohort 1

Drug: Low-dose OKN-007, BID

Low-dose OKN-007, three times a day (TID)

EXPERIMENTAL

Dose Escalation Cohort 2

Drug: Low-dose OKN-007, TID

Mid-dose OKN-007, three times a day (TID)

EXPERIMENTAL

Dose Escalation Cohort 3

Drug: Mid-dose OKN-007, TID

High-dose OKN-007, three times a day (TID)

EXPERIMENTAL

Dose Escalation Cohort 4

Drug: High-dose OKN-007, TID

Interventions

Low-dose OKN-007, BID DRUG

Participants will be administered low doses of oral OKN-007 two times a day daily in 28-day cycles.

Low-dose OKN-007, two times a day (BID)

Low-dose OKN-007, TID DRUG

Participants will be administered low doses of oral OKN-007 three times a day daily in 28-day cycles.

Low-dose OKN-007, three times a day (TID)

Mid-dose OKN-007, TID DRUG

Participants will be administered mid doses of oral OKN-007 three times a day daily in 28-day cycles.

Mid-dose OKN-007, three times a day (TID)

High-dose OKN-007, TID DRUG

Participants will be administered high doses of oral OKN-007 three times a day daily in 28-day cycles.

High-dose OKN-007, three times a day (TID)

Eligibility Criteria

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

You may qualify if:

• Confirmed recurrent gliomas that were originally diagnosed as high-grade glioma (World Health Organization \[WHO\] Grade 3 or 4; astrocytoma, oligodendroglioma, or glioblastoma) by histopathology or molecular studies.
• Progressive or recurrent gliomas documented by magnetic resonance imaging (MRI) no earlier than 180 days after first surgery for gliomas and no earlier than 90 days after completion of radiotherapy (applies to patients with first progression/recurrence only).
• Patients must have medical records available documenting known histology or molecular and genetic information resulting from prior analyses, or tumor tissue samples available from prior glioma surgery or open biopsy for correlative research.
• For patients with unresected recurrent tumor, unequivocal radiographic evidence of tumor progression by MRI as per the RANO criteria within 28 days prior to the first dose. These patients must have at least one measurable lesion per RANO.
• No more than two prior lines of therapy for high-grade glioma (WHO Grade 3 or 4). The first-line therapy must include radiotherapy (minimum of 50 Gy; 34 Gy in elderly patients) with concomitant or adjuvant standard chemotherapy (temozolomide (TMZ), or procarbazine, lomustine and vincristine in patients with anaplastic oligodendroglioma).
• Eastern Cooperative Oncology Group (ECOG) performance status \<2.
• Full recovery (grade ≤1) from the toxic effects of any earlier intervention and a minimum of 28 days from the last administration of any investigational agent that has not received regulatory approval for any indication at the time of registration.
• Adequate renal, liver and bone marrow function without packed red blood cell/platelet transfusions within 4 weeks of the date of lab test during screening:
• Leukocytes ≥3.0 × 10\^9/L
• Absolute neutrophil count (ANC) ≥1.5 × 10\^9/L
• Platelets ≥100 × 10\^9/L
• Hemoglobin ≥ 9.0 g/dL
• Total bilirubin ≤1.5 × upper limit of normal (ULN), unless documented Gilbert's syndrome.
• Aspartate transaminase/alanine transaminase ≤2.5 × ULN
• Creatinine clearance ≥60 mL/min calculated as per Cockcroft-Gault equation.

You may not qualify if:

• Prior malignancy (other than glioma) expected to require treatment within a 6-month period (except adequately treated basal cell carcinoma of the skin). Patients who had another malignancy in the past but have been free of active disease for more than 2 years, are eligible.
• Have received treatment within the last 28 days with a drug that has not received regulatory approval for any indication at the time of study registration.
• Have received chemotherapeutic agents (including TMZ) within 28 days or within 5 half-lives for non-cytotoxic agents (whichever is shorter) of study registration.
• Serious concomitant systemic disorders, for example, abnormal electrocardiogram (ECG) indicative of cardiac disease (patients with Fridericia-corrected QT interval \[QTcF\] \>480 msec.
• Patients with abnormal sodium, potassium, or creatinine levels grade ≥2.
• Inability to comply with protocol or study procedures.
• Women who are pregnant or breastfeeding.
• Patients who have received bevacizumab for recurrent glioblastoma or are planning to initiate treatment with bevacizumab for tumor necrosis.
• Patients completing radiotherapy treatment less than 2 weeks prior to planned study treatment initiation.

Sponsors & Collaborators

• Oblato, Inc.: lead

Study Sites (4)

Providence Saint John's Cancer Institute

Santa Monica, California, 90404, United States

Location

Norton Healthcare

Louisville, Kentucky, 40202, United States

Location

Atrium Health Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

Location

The University of Oklahoma Health Sciences Center, Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

MeSH Terms

Conditions

Glioma; Oligodendroglioma; Astrocytoma; Glioblastoma

Interventions

OKN 007; BID protein, human

Condition Hierarchy (Ancestors)

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

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: September 22, 2022
• First Posted: September 30, 2022
• Study Start: April 17, 2023
• Primary Completion: May 31, 2025
• Study Completion: June 30, 2025
• Last Updated: November 29, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)