TBD11 Safety Study in Healthy Adults

Overseen By Gates MRI

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Bill & Melinda Gates Medical Research Institute

Must not be taking: Opioids, Amphetamines

Disqualifiers: Cardiovascular disease, Cancer, Drug abuse, others

Compensation: Varies

Number of Visits: 26

124 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TBD11, an experimental therapy, to determine its safety for people. Researchers are trying it on humans for the first time and aim to learn how the body processes it, both with and without food. The trial has two main parts: the first involves single doses, and the second involves multiple doses. It seeks healthy individuals who can stay at the research facility during the study period. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects on people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the trial is for healthy adults, it's possible that taking certain medications might affect eligibility. Please consult with the trial staff for specific guidance.

Is there any evidence suggesting that TBD11 is likely to be safe for humans?

Research shows that TBD11 is being tested in humans for the first time. This Phase 1 trial aims to determine if the drug is safe for healthy adults. Specific information on how participants are handling TBD11 is not yet available, but Phase 1 trials focus on safety before advancing to more complex research. Researchers will carefully monitor and manage any major side effects. Participants in these early studies typically receive smaller doses to help understand the drug's safe use. Those who join this trial will be in a controlled setting where their health is closely monitored. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about TBD11 because it offers a fresh approach to treatment. Unlike existing therapies that work through traditional pathways, TBD11 might have a novel mechanism of action that targets the condition differently, potentially leading to more effective outcomes. Additionally, the trial is exploring how food affects the absorption of TBD11, which could provide insights into optimizing its administration. These unique features give researchers hope that TBD11 could represent a significant advancement over current treatment options.

What evidence suggests that TBD11 could be an effective treatment?

Research has shown that TBD11 is a promising new treatment for tuberculosis (TB). Studies have found that it might work by stopping the bacteria from growing. Early results suggest that TBD11 remains in the body long enough to be effective and is generally well tolerated, which could help patients adhere to their treatment and improve their health. These early signs indicate that TBD11 could help reduce the spread of TB, especially in low- and middle-income countries where TB is most common. Participants in this trial will receive either TBD11 or a placebo to further evaluate its safety and effectiveness. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for healthy adults who can participate in a study to test the safety and behavior of a new substance called TBD11. Specific eligibility details are not provided, but typically participants must meet certain health standards.

Inclusion Criteria

Can understand and comply with the trial and site procedures, understand the risks involved in the trial, and provide written informed consent before the first trial-specific procedure

Is healthy as determined by the Investigator via medical history and clinical examination before enrolment in the trial

Has resting vital signs within specified ranges for systolic and diastolic blood pressure, and heart rate

Exclusion Criteria

I have a condition that might affect how my body handles medication.

Has history of any drug abuse within 1 year prior to Screening or has used any hard drugs within 1 year prior to Screening

I have a significant health condition as determined by my doctor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Single Ascending Dose (SAD)

Participants receive single ascending doses of TBD11 or placebo

1 week

Daily visits for 7 days

Food Effect (FE) and Bioequivalence (BE)

Open-label evaluation of food effect and alternative formulation of TBD11

3 weeks

Multiple visits including washout periods

Multiple Ascending Dose (MAD)

Participants receive multiple ascending doses of TBD11 or placebo

19 days

Daily visits for 19 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TBD11

Trial Overview TBD11 is being tested against a placebo in this first-in-human trial. It's randomized and double-blind, meaning neither the researchers nor participants know who gets what. The study has two parts: one with single doses and another with multiple doses.

How Is the Trial Designed?

Group I: TBD11 Experimental Treatment 2 Interventions

In Part 1 double-blind phase of the trial (SAD), cohorts 1 to 5 and cohort 7 will receive doses of TBD11; 8 participants in each cohort will be randomized (6:2) to receive TBD11 or placebo. The FE component of Part 1 (cohort 6) is open-label and 12 participants will receive TBD11 to evaluate the food effect. In Part 2, double blind phase of the trial, MAD, 48 participants will be randomized (3:1) to receive TBD11 or placebo in Cohorts 1-3. In Part 2 (Cohort 4), all participants will receive open-label TBD11

Group II: Placebo Placebo Group 1 Intervention

Participants in Part 1 (cohorts 1-5 and cohort 7) and Part 2 will receive placebos matched to TBD11

Who Is Running the Clinical Trial?

Bill & Melinda Gates Medical Research Institute

Lead Sponsor

Trials

15

Recruited

30,900+

Gates Medical Research Institute

Lead Sponsor

Published Research Related to This Trial

In a comprehensive review of 54 phase-I studies involving 1015 healthy volunteers over 10 years, the overall incidence of adverse events was found to be 12.8%, with a higher rate for active drugs (13.7%) compared to placebo (7.9%).

Most adverse events were minor, with only 3% classified as severe, and no deaths or life-threatening events reported, highlighting that while adverse events are common in phase-I trials, they are typically not serious.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in phase-I studies: a report in 1015 healthy volunteers. Sibille, M., Deigat, N., Janin, A., et al.[2019]

The recent fatal adverse event in the BIA-102474-101 clinical trial highlights significant limitations in the current safety review process for first-into-human trials, despite previous trials with similar compounds being conducted without incident.

To improve safety in future trials, it is crucial to implement sequential dosing strategies, thorough reviews of preclinical toxicity studies, and systematic risk assessments, especially for novel compounds that may pose higher risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications of the BIA-102474-101 study for review of first-into-human clinical trials. Eddleston, M., Cohen, AF., Webb, DJ.[2021]

The study evaluated 36 drugs known to cause idiosyncratic adverse drug reactions (IADRs) using an in vitro approach that combined cellular toxicity assays and covalent binding assessments, achieving high specificity (78%) and sensitivity (100%) in distinguishing drugs with high IADR risk from those with low risk.

This integrated method could help in selecting drug candidates with a lower likelihood of causing IADRs, potentially improving drug safety during development and after market approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro approach to assess the potential for risk of idiosyncratic adverse reactions caused by candidate drugs. Thompson, RA., Isin, EM., Li, Y., et al.[2021]

In a meta-analysis of 11,028 healthy participants across 394 non-oncology phase I studies, 63.7% experienced adverse events, but 85% of these were classified as mild, indicating a relatively safe profile for the study drugs.

Only 0.31% of participants experienced serious adverse events, with no deaths or life-threatening incidents reported, suggesting that while adverse events are common, they are mostly not severe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantifying the risks of non-oncology phase I research in healthy volunteers: meta-analysis of phase I studies. Emanuel, EJ., Bedarida, G., Macci, K., et al.[2018]

In a survey of 20 companies, it was found that there are four different approaches to reporting toxic/adverse dose levels in first-in-human (FIH)-enabling toxicology studies for anticancer drugs, with 45% of companies reporting the highest non-severely toxic dose (HNSTD) or the dose severely toxic to 10% (STD10).

The study highlights the importance of defining a consistent reporting approach before starting toxicology studies, as this can impact regulatory acceptance and the safety assessment of new anticancer pharmaceuticals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicologic Pathology Forum: Opinion on Approaches for Reporting Toxic and Adverse Dose Levels in Nonclinical Toxicology Studies Supporting the Development of Anticancer Pharmaceuticals. Hukkanen, RR., Moriyama, T., Patrick, DJ., et al.[2023]

Citations

1. linkedin.com linkedin.com/posts/gates-medical-research-institute_our-team-recently-began-a-phase-1-clinical-activity-7284573672223174656-Xvbs

Gates Medical Research Institute's Post If successful, TBD11 could significantly contribute to addressing TB, especially in low- and middle-income countries where the burden of the ...

2. newtbdrugs.org newtbdrugs.org/sites/default/files/meetings/files/07_David%20Holtzman_Gates%20Medical%20Research%20Institute.pdf

Gates MRI TB Drug Development Activities No baseline or ongoing safety monitoring. Enables Test & Treat. Well tolerated → Improves Adherence → Improves Outcomes → Less Transmission.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0960894X25000174

Novel isoxazole thiophene-containing compounds active ... A novel isoxazole thiophene hit as a putative Rv1625c/Cya activator with a promising in vitro activity and good pharmacokinetic properties.

4. c-path.org c-path.org/pan-tb/

PAN-TB The PAN-TB datasets are designed to catalyze and accelerate tuberculosis (TB) research by curating and standardizing Pharmacokinetic and relapsing mouse model ( ...

5. reporter.nih.gov reporter.nih.gov/search/14ez7JpOHUm2iMlgMsRlWg/project-details/11192197

RePORT ⟩ RePORTER We're sorry but RePORTER doesn't work properly without JavaScript enabled. Please enable it to continue.

6. ctv.veeva.com ctv.veeva.com/study/a-trial-in-healthy-adult-participants-to-evaluate-the-safety-tolerability-and-behavior-in-the-body

A Trial in Healthy Adult Participants to Evaluate the Safety ... This is a randomized, double-blind, placebo controlled First in human (FIH) trial of TBD11, administered to healthy adults.

7. synapse.patsnap.com synapse.patsnap.com/drug/a93cc27631914d20b839cc90d7d742fe

TBD-11 - Drug Targets, Indications, Patents ... Healthy Adult Participants to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBD11 With an Open Label (Single Dose) Food Effect ...

8. trial.medpath.com trial.medpath.com/clinical-trial/becbb3cc749f2732/nct06707142-safety-tolerability-pharmacokinetics-tbd11

A Trial in Healthy Adult Participants to Evaluate the Safety ... This is a randomized, double-blind, placebo controlled First in human (FIH) trial of TBD11, administered to healthy adults. The trial will be conducted in ...

9. withpower.com withpower.com/clinical-trials/for-tb

Top Tb Clinical Trials | Power TBD11 Safety Study in Healthy Adults. Lincoln, Nebraska. This is a randomized, double-blind, placebo controlled First in human (FIH) trial of TBD11 ...