TBD11 Safety Study in Healthy Adults

Overseen By Gates MRI

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Bill & Melinda Gates Medical Research Institute

Must not be taking: Opioids, Amphetamines

Disqualifiers: Cardiovascular disease, Cancer, Drug abuse, others

Trial Summary

What is the purpose of this trial?

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 two parts. Part 1 will consist of single ascending dose (SAD) and Food effect (FE) cohorts, and Part 2 will consist of multiple ascending dose (MAD) cohorts.

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.

What safety data exists for TBD11 in humans?

There is no specific safety data available for TBD11 in humans from the provided research articles. ^{1 2 3 4 5}

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• TBD11 (Other)

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.

Participant Groups

Group I: TBD11 Experimental Treatment 2 Interventions

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

Group II: Placebo Placebo Group 1 Intervention

Participants in in Part 1 (cohorts 1-5 and optional 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+

Findings from Research

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]

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]

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]

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]

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]

References

1. United States 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. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Adverse events in phase-I studies: a report in 1015 healthy volunteers. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Quantifying the risks of non-oncology phase I research in healthy volunteers: meta-analysis of phase I studies. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

In vitro approach to assess the potential for risk of idiosyncratic adverse reactions caused by candidate drugs. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Implications of the BIA-102474-101 study for review of first-into-human clinical trials. [2021]