ORC-13661 for Preventing Ototoxicity

Recruiting at 4 trial locations

Overseen By Alyssa Schroeder

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kevin Winthrop

Must be taking: IV amikacin

Must not be taking: CYP3A4 inducers, CYP3A4 inhibitors

Disqualifiers: Amikacin exposure, Congenital hearing loss, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12-13 weeks

105 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, ORC-13661, to determine if it can prevent or reduce hearing loss caused by the antibiotic amikacin, used to treat a lung infection called NTM. Participants will be divided into three groups: two receiving different doses of ORC-13661 and one taking a placebo (a non-active substance). The goal is to assess the effectiveness of ORC-13661 and whether the dose affects outcomes. Ideal participants have an NTM infection, are scheduled to receive amikacin for at least 30 days, and have not recently used similar antibiotics. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Do I need to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot take certain drugs like strong CYP3A4 inducers or inhibitors during the study. It's best to discuss your current medications with the study team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ORC-13661 can protect hearing by blocking certain processes in the ear that cause damage when taking antibiotics like amikacin. So far, studies have not identified any major safety concerns with ORC-13661.

The current study is in an early phase, so researchers are still assessing how well people tolerate the treatment. This phase primarily evaluates the safety and side effects of the treatment. While ORC-13661 remains under investigation, earlier findings suggest it is likely safe. Participants in this trial will help confirm its safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ORC-13661 because it offers a new way to prevent ototoxicity, which is hearing damage often caused by certain antibiotics like amikacin. Unlike typical treatments that don't specifically protect hearing, ORC-13661 is designed to directly prevent this side effect. The drug works by using a unique active ingredient that could potentially shield the inner ear from damage. This proactive approach could make a big difference for patients who need these powerful antibiotics but want to avoid the risk of hearing loss.

What evidence suggests that this trial's treatments could be effective for preventing hearing loss?

Studies have shown that ORC-13661 can protect against hearing damage caused by certain antibiotics, such as amikacin. It blocks the process that harms the tiny hair cells in the ear, which are essential for hearing. Research indicates that ORC-13661 can effectively prevent hearing loss in this manner. In this trial, participants will receive either a low dose or a high dose of ORC-13661, or a placebo, to evaluate its effectiveness in reducing the risk of hearing problems in patients receiving amikacin treatment. This makes ORC-13661 a promising option for protecting hearing health. ^{1 2 3 6 7}

Who Is on the Research Team?

Kevin L Winthrop, MD, MPH

Principal Investigator

Oregon Health and Science University

Edwin Rubel, PhD

Principal Investigator

Oricula Therapeutics

Are You a Good Fit for This Trial?

Adults aged 18-80 with NTM infection requiring IV amikacin treatment, who can take oral medication and follow the study's procedures. They must not have had amikacin in the last 6 months or known resistance to it. Participants need effective contraception if of reproductive potential and cannot be pregnant, lactating, or under correctional supervision.

Inclusion Criteria

Providing informed consent, documented by signing and dating the currently valid informed consent form

I agree to use effective contraception or practice abstinence for 3 months after the last dose.

I will be on IV amikacin for at least 30 days starting now.

Exclusion Criteria

Presence of any circumstance, condition, ECG or laboratory finding that, based on investigator judgment, would interfere with study procedures or assessments or present to the patient an unreasonable risk from participation in this study

I am taking clofazimine or bedaquiline and have heart issues or low potassium.

Pregnant or lactating

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either high-dose ORC-13661, low-dose ORC-13661, or placebo concurrently with IV amikacin for up to 90 days

12-13 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ORC-13661
• Placebo

Trial Overview The trial is testing ORC-13661's ability to prevent hearing loss from IV amikacin therapy in NTM patients. It compares two different doses of ORC-13661 against a placebo over at least 30 days. Researchers will monitor participants' hearing and overall health during this period.

How Is the Trial Designed?

Group I: Low Dose ORC-13661 Experimental Treatment 1 Intervention

This arm is a daily treatment regimen of study drug (ORC-13661) with a loading dose of 60mg capsules followed by a daily dose of 12mg capsules. Treatment regimen will run concurrently with treatment with IV amikacin. Study drug treatment will continue until treatment with IV amikacin ends or 90 days, whichever is earlier.

Group II: High Dose ORC-13661 Experimental Treatment 1 Intervention

This arm is a daily treatment regimen of study drug (ORC-13661) with a loading dose of 150mg followed by a daily dose of 30mg. Treatment regimen will run concurrently with treatment with IV amikacin. Study drug treatment will continue until treatment with IV amikacin ends or 90 days, whichever is earlier.

Group III: Placebo Placebo Group 1 Intervention

This arm is a daily treatment regimen of a placebo with a loading dose and a daily dose of placebo capsules to match the treatment arms. Placebo regimen will run concurrently with treatment with IV amikacin. Placebo regimen will continue until treatment with IV amikacin ends or 90 days, whichever is earlier.

Who Is Running the Clinical Trial?

Kevin Winthrop

Lead Sponsor

Trials

4

Recruited

760+

Oricula Therapeutics

Collaborator

Trials

1

Recruited

110+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

National Institute on Deafness and Other Communication Disorders (NIDCD)

Collaborator

Trials

377

Recruited

190,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

National Jewish Health

Collaborator

Trials

145

Recruited

318,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

The University of Texas Health Science Center at Tyler

Collaborator

Trials

15

Recruited

25,700+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6693895/

ORC-13661 protects sensory hair cells from ... ORC-13661 robustly protects against ototoxicity by aminoglycoside antibiotics and cisplatin by reversibly blocking mechanotransduction of sensory hair cells.

2. trial.medpath.com trial.medpath.com/clinical-trial/ac9189ee7c89014c/efficacy-safety-ORC-13661-hearing-loss-prevention

Prevention of Ototoxicity in NTM Patients Treated With IV Amikacin ... This main goal of this study is to test the effectiveness of the study drug, ORC-13661, a small molecule compound being developed as an adjunct therapy to be ...

3. reporter.nih.gov reporter.nih.gov/search/JTL5ueAA3EivxtyPGYtArA/project-details/10900457

Project Details - NIH RePORTER Oral ORC-13661was developed from a small molecule screen aimed finding a way to mitigate AG-induced hair cell toxicity. It is robustly effective at preventing ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05730283/prevention-of-ototoxicity-in-ntm-patients-treated-with-iv-amikacin

Prevention of Ototoxicity in NTM Patients Treated With IV ... The main question this study aims to answer is: Is ORC-13661 effective for preventing or lessening hearing loss induced by amikacin treatment?

5. withpower.com withpower.com/trial/phase-2-ototoxicity-7-2023-80f61

ORC-13661 for Preventing Ototoxicity This trial is testing a drug called ORC-13661 to see if it can prevent hearing loss in older patients with a lung infection who are being treated with ...

6. reporter.nih.gov reporter.nih.gov/search/6cX7XxLR7k-82nFfE5XCxg/project-details/11195429

Project Details - NIH RePORTER Developing ORC-13661 for Preventing Aminoglycoside Antibiotics-induced Hearing Loss ... Phase 2 Study of the Efficacy and Safety of ORC-13661 for the Prevention ...

7. medsci.org medsci.org/v22p0732.htm

Protective effects of MET channels on aminoglycosides But compounds such as ORC-13661 and UoS-7692 have also been shown to provide protection against ototoxicity without affecting the antitumor and antibacterial ...