High-grade GliomaPhase 1NCT05561374
Study of Safety and Pharmacokinetic Properties of Oral OKN-007 in Patients with Recurrent High-Grade Glioma
A Phase 1 study testing Low-dose OKN-007, BID, Low-dose OKN-007, TID and Mid-dose OKN-007, TID in people with High-grade Glioma and Oligodendroglioma, run by Oblato, Inc. at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- High-grade Glioma, Oligodendroglioma, Astrocytoma
- What is being tested?
- Low-dose OKN-007, BID, Low-dose OKN-007, TID and Mid-dose OKN-007, TID
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 4 sitesUnited States
- Study dates
- 17 Apr 2023to 30 Jun 2025
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Patients must be ≥18 years of age.
- Life expectancy (as assessed by the Investigator) at least three months.
- Patients must not have significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea, or inability to swallow oral medications.
- Have provided written informed consent.
- Patients must be willing to have multiple blood draws for PK analysis.
- Female patients, of childbearing potential, must have a negative serum pregnancy test within 7 days prior to study treatment initiation and agree to use adequate contraception or practice sexual abstinence as the preferred and usual lifestyle of the patient during the study and for up to 120 days (4 months) after the last dose of study treatment.
- Male patients with female partners of childbearing potential must, even if surgically sterilized, agree to practice effective barrier contraception and practice true abstinence.
- Human immunodeficiency virus infected patients on effective antiretroviral therapy with undetectable viral load within 6 months prior to study registration are eligible for this trial.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Norton Healthcare
Louisville, Kentucky, 40202
The University of Oklahoma Health Sciences Center, Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Providence Saint John's Cancer Institute
Santa Monica, California, 90404
Atrium Health Wake Forest Baptist Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157
About this study
Official title: A Phase 1b Open-Label Study Investigating the Tolerability, Safety, and Pharmacokinetic Properties of Oral OKN-007 in Patients with Recurrent High-Grade Glioma
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.
Read the detailed description
This phase 1 open-label study is based on the traditional 3+3 design following the initial single-participant cohort to determine the maximum tolerated dose (MTD). Eligible participants will be enrolled each of the cohorts with escalated dose levels and administered the study drug OKN-007 orally daily in 28-day cycles: Cohort 1, Cohort 2, Cohort 3, Cohort 4. Participants may receive study treatment up to 2 years or until tumor progression, unacceptable toxicity, death, or patient withdrawal. The safety and pharmacokinetic properties of oral OKN-007 will be investigated.
- Being tested
- Low-dose OKN-007, BID, Low-dose OKN-007, TID, Mid-dose OKN-007, TID, High-dose OKN-007, TID
- Medical subject headings
- Glioma, Oligodendroglioma, Astrocytoma, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-dose OKN-007, BIDDrug
Participants will be administered low doses of oral OKN-007 two times a day daily in 28-day cycles.
Low-dose OKN-007, TIDDrug
Participants will be administered low doses of oral OKN-007 three times a day daily in 28-day cycles.
Mid-dose OKN-007, TIDDrug
Participants will be administered mid doses of oral OKN-007 three times a day daily in 28-day cycles.
High-dose OKN-007, TIDDrug
Participants will be administered high doses of oral OKN-007 three times a day daily in 28-day cycles.
| Study group | Role | What they receive |
|---|---|---|
| Low-dose OKN-007, two times a day (BID) | Experimental | Dose Escalation Cohort 1 Receives: Drug: Low-dose OKN-007, BID |
| Low-dose OKN-007, three times a day (TID) | Experimental | Dose Escalation Cohort 2 Receives: Drug: Low-dose OKN-007, TID |
| Mid-dose OKN-007, three times a day (TID) | Experimental | Dose Escalation Cohort 3 Receives: Drug: Mid-dose OKN-007, TID |
| High-dose OKN-007, three times a day (TID) | Experimental | Dose Escalation Cohort 4 Receives: Drug: High-dose OKN-007, TID |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability: Adverse events
Safety and tolerability will be evaluated from adverse events as reported according to CTCAE version 5.0.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2022
- Study start17 Apr 2023
- Primary completion31 May 2025 (estimated)
- Study completion30 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High-grade GliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oblato, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05561374
- Sponsor's protocol ID
- OKN-007-OL-RMG-101
- Status last verified
- Nov 2024
- First submitted
- 22 Sep 2022
- Last updated
- 29 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Open-Label Study Investigating the Tolerability, Safety, and Pharmacokinetic Properties of Oral OKN-007 in Patients with Recurrent High-Grade Glioma
- ClinicalTrials.gov ID
- NCT05561374
- Acronym / sponsor ID
- OKN-007-OL-RMG-101
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Oblato, Inc.Industry (pharma, biotech, devices)
- Study start
- 17 Apr 2023 (actual)
- Primary completion
- 31 May 2025 (estimated)
- Study completion
- 30 Jun 2025 (estimated)
- First posted
- 30 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This phase 1 open-label study is based on the traditional 3+3 design following the initial single-participant cohort to determine the maximum tolerated dose (MTD). Eligible participants will be enrolled each of the cohorts with escalated dose levels and administered the study drug OKN-007 orally daily in 28-day cycles: Cohort 1, Cohort 2, Cohort 3, Cohort 4. Participants may receive study treatment up to 2 years or until tumor progression, unacceptable toxicity, death, or patient withdrawal. The safety and pharmacokinetic properties of oral OKN-007 will be investigated.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Low-dose OKN-007, two times a day (BID) | Experimental | Drug: Low-dose OKN-007, BIDDose Escalation Cohort 1 |
| Low-dose OKN-007, three times a day (TID) | Experimental | Drug: Low-dose OKN-007, TIDDose Escalation Cohort 2 |
| Mid-dose OKN-007, three times a day (TID) | Experimental | Drug: Mid-dose OKN-007, TIDDose Escalation Cohort 3 |
| High-dose OKN-007, three times a day (TID) | Experimental | Drug: High-dose OKN-007, TIDDose Escalation Cohort 4 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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).
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low-dose OKN-007, BIDParticipants will be administered low doses of oral OKN-007 two times a day daily in 28-day cycles. | Drug | Low-dose OKN-007, two times a day (BID) |
| Low-dose OKN-007, TIDParticipants will be administered low doses of oral OKN-007 three times a day daily in 28-day cycles. | Drug | Low-dose OKN-007, three times a day (TID) |
| Mid-dose OKN-007, TIDParticipants will be administered mid doses of oral OKN-007 three times a day daily in 28-day cycles. | Drug | Mid-dose OKN-007, three times a day (TID) |
| High-dose OKN-007, TIDParticipants will be administered high doses of oral OKN-007 three times a day daily in 28-day cycles. | Drug | High-dose OKN-007, three times a day (TID) |
Primary outcome
Safety and tolerability: Adverse events
Time frame: From Day 1 to 30 days after the last treatment
Safety and tolerability will be evaluated from adverse events as reported according to CTCAE version 5.0.
Pharmacokinetic profile: Maximum plasma concentration (Cmax)
Time frame: 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)
Maximum plasma concentration (Cmax) will be calculated using the actual sample collection times.
Pharmacokinetic profile: Time to Cmax (Tmax)
Time frame: 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)
Time to Cmax (Tmax) will be calculated using the actual sample collection times.
Pharmacokinetic profile: Area under the curve (AUC)
Time frame: 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)
Area under the curve (AUC) will be calculated using the actual sample collection times.
Pharmacokinetic profile: Half-life time (t1/2)
Time frame: 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)
Half-life time (t1/2) will be calculated using the actual sample collection times.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Low-dose OKN-007, BID, Low-dose OKN-007, TID and Mid-dose OKN-007, TID in people with High-grade Glioma and Oligodendroglioma, run by Oblato, Inc. at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability: Adverse events (time frame: From Day 1 to 30 days after the last treatment). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2024.