AFA-281 Safety Study in Healthy Volunteers

Overseen By Dennis Gilman, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Afasci Inc

Disqualifiers: Significant medical history, others

Compensation: Varies

Number of Visits: 72

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to test the safety and tolerability of a new treatment called AFA-281 in healthy individuals. Participants will take AFA-281 as an oral capsule to observe how the body processes it and to identify any side effects. The study consists of two parts: first, a single dose, followed by multiple doses over two weeks. Participants must be in good health, have no major medical issues, and fit within a Body Mass Index (BMI) range of 18.0 to 30.0. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial is for healthy volunteers with no significant medical history, it's likely that participants should not be on any regular medications.

Will I have to stop taking my current medications?

The trial is for healthy volunteers with no significant medical history, which suggests that participants should not be on any current medications. The protocol does not specify a requirement to stop taking medications, but it implies that participants should not be taking any.

Is there any evidence suggesting that AFA-281 is likely to be safe for humans?

Research has shown that AFA-281 is likely safe. Studies have found that the body absorbs it well when taken orally. In animal tests, AFA-281 did not cause heart-related side effects. These results suggest that AFA-281 is safe enough for human testing.

Although data from humans is not yet available, the initiation of this trial indicates confidence in its safety based on earlier lab and animal studies. As the trial progresses, researchers will gather more information to better understand its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

AFA-281 is unique because it is an oral capsule that researchers are testing at multiple dose levels, offering a potential new way to address the condition it's targeting. Unlike many treatments that might require longer periods to demonstrate effectiveness, AFA-281 is being evaluated for its potential to show results more quickly, especially in Part 2 of the study where it's administered twice daily for 14 days. This new approach could make it more convenient and efficient compared to existing options. Researchers are excited because if successful, AFA-281 could provide a more rapid and accessible treatment option for patients.

What evidence suggests that AFA-281 might be an effective treatment?

Research has shown that AFA-281 has been promising in early animal studies. It provided significant pain relief and reduced brain inflammation in rats with nerve injuries. This suggests that AFA-281 might help with pain conditions in humans. However, specific data from human studies on its effectiveness is not yet available. In this trial, participants will receive either AFA-281 or a placebo. The trial will assess how the body processes the drug and its safety in humans, which are important first steps. ^{1 2 5 6 7}

Who Is on the Research Team?

Xinmin Xie, MD, PhD

Principal Investigator

Afasci Inc

Are You a Good Fit for This Trial?

This trial is for healthy volunteers with a BMI between 18.0 and 30.0, no significant medical history, normal lab values, and a normal ECG. People with any significant health issues or abnormal test results cannot participate.

Inclusion Criteria

Your heart test (ECG) should not show any important problems.

Your body mass index (BMI) must be between 18.0 and 30.0 kg/m2.

I am in good health with no major medical issues.

Exclusion Criteria

You have significant abnormal medical conditions.

Participants with significant medical history or clinically significant abnormalities

You have abnormal results on an ECG test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Part 1: Single Ascending Dose

Healthy volunteers receive a single ascending dose of AFA-281 or placebo. Safety, tolerability, and pharmacokinetics are evaluated.

1 week

Daily visits for up to 72 hours post-dose

Phase I Part 2: Multiple Ascending Doses

Pending results from Part 1, volunteers receive multiple doses of AFA-281 or placebo for 14-21 days. Safety, tolerability, and pharmacokinetics are evaluated.

2-3 weeks

Routine clinical monitoring throughout the dosing period

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AFA-281

Trial Overview

The study tests AFA-281 in two parts: Part 1 gives single doses to groups of volunteers to check safety and how the body processes the drug. If safe, Part 2 has them take it for 14 days to further assess these factors.

How Is the Trial Designed?

Group I: AFA-281 Experimental Treatment 1 Intervention

Part 1: AFA-281 administered as an oral capsule at 5 dose levels for one day. Part 2: AFA-281 administered as an oral capsule at 3 dose levels twice daily for 14 consecutive days. Doses will be determined after completion of Part 1.

Group II: Placebo Control Placebo Group 1 Intervention

Double blind placebo control

Who Is Running the Clinical Trial?

Afasci Inc

Lead Sponsor

Trials

4

Recruited

490+

Cognitive Research Corporation

Industry Sponsor

Trials

25

Recruited

2,400+

Published Research Related to This Trial

In a study of 182 patients aged 20-69 with femoral neck fractures treated with internal fixation, 73% of those with displaced fractures and 85% with non-displaced fractures reported good or excellent functional outcomes at 24 months.

Despite a significant percentage achieving good functional outcomes, patients did not fully regain their pre-fracture health-related quality of life, indicating that while surgical intervention is effective, it may not restore overall quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Good functional outcome but not regained health related quality of life in the majority of 20-69 years old patients with femoral neck fracture treated with internal fixation: A prospective 2-year follow-up study of 182 patients. Campenfeldt, P., Hedström, M., Ekström, W., et al.[2018]

In a review of 24 First-in-Man studies involving 1,017 healthy male volunteers, the incidence of adverse events (AEs) was low, with 98.3% of AEs being mild or moderate, indicating a favorable safety profile for small molecules in Phase I trials.

Only 0.4% of treatments resulted in serious adverse events, all of which were not medically concerning and did not require hospitalization, suggesting that small molecule trials can be conducted safely in healthy volunteers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of healthy volunteers in First-in-Man trials - an analysis of studies conducted at the Bayer in-house ward from 2000 to 2005. Wensing, G., Ighrayeb, IA., Boix, O., et al.[2019]

In a five-year analysis of 1,559 healthy volunteers across 142 phase I studies, the overall incidence of adverse events (AEs) was 8.8%, with most AEs being mild or moderate in severity, indicating that while AEs are common, they are generally not severe.

The incidence of AEs was significantly higher in multiple-dose studies compared to single-dose trials, highlighting the importance of study design in assessing the safety profile of active drugs, with a notable increase in AEs on the first day of drug administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in volunteers participating in phase I clinical trials: a single-center five-year survey in 1,559 subjects. Lutfullin, A., Kuhlmann, J., Wensing, G.[2019]

In a study involving 2990 potential volunteers across seven African sites, 2387 (80%) were enrolled, but only 2107 (71%) were included in the final analysis due to various health-related exclusions, highlighting the importance of health screening in clinical trials.

The study found that a significant number of volunteers were excluded from analysis due to positive tests for Hepatitis B and C, as well as abnormal physical examination findings, indicating the need for tailored health assessments in African populations participating in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline morbidity in 2,990 adult African volunteers recruited to characterize laboratory reference intervals for future HIV vaccine clinical trials. Stevens, W., Kamali, A., Karita, E., et al.[2022]

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 study of 120 healthy young adults, the intrinsic extension reserve (IER) of the hip joint was found to vary significantly among different sagittal alignment subtypes, indicating that spinal alignment can influence hip extension capacity.

The study revealed that individuals with a greater sacral slope had a higher range of motion in both the pelvis and hip joint, suggesting that pelvic alignment may play a crucial role in hip extension mechanics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hip-Spine Relationship between Sagittal Balance of the Lumbo-Pelvi-Femoral Complex and Hip Extension Capacity: An EOS Evaluation in a Healthy Caucasian Population. Kouyoumdjian, P., Mansour, J., Haignère, V., et al.[2023]

Human volunteer studies are crucial for gathering data on the biokinetics and metabolism of compounds, which is essential for accurate human risk assessment.

These studies can enhance the reliability of extrapolating results from animal studies to humans, helping to fill knowledge gaps that in vitro or animal studies cannot address.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Healthy volunteer studies in toxicology. Meulenbelt, J., Mensinga, TT., Kortboyer, JM., et al.[2019]

Surgical patients are significantly more willing to ask factual questions about their care than challenging questions, indicating a need for strategies to empower patients to engage more actively in their healthcare.

Patients who received instructions from doctors were more likely to ask challenging questions, suggesting that healthcare staff can play a crucial role in encouraging patient involvement in safety discussions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How willing are patients to question healthcare staff on issues related to the quality and safety of their healthcare? An exploratory study. Davis, RE., Koutantji, M., Vincent, CA.[2022]

In a study of 100 hospitalized flu patients (50 in isolation and 50 not), the incidence of adverse events (AEs) was found to be lower in those undergoing isolation measures, with significant differences in AE identification based on the observer's definition of a case.

The study highlighted the importance of inter-observer agreement in identifying AEs, showing good agreement for screening (over 76% Kappa index) but lower agreement for accurately identifying AEs related to care, indicating that methodology is crucial for reliable epidemiological studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Identification of adverse events in hospitalised influenza patients]. Aranaz-Andrés, JM., Gea-Velázquez de Castro, MT., Jiménez-Pericás, F., et al.[2017]

A study involving 134 patients found that 90% rated the animated video on patient safety as good or very good, while 100% of those receiving oral information felt the same, indicating high satisfaction with both methods.

Despite the positive feedback for the video, 74% of patients who received both formats preferred the oral presentation, suggesting that while videos can enhance understanding, they should not replace traditional verbal communication for optimal patient engagement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Communicating Patient Safety Information Through Video and Oral Formats-A Comparison. Bånnsgård, M., Nouri, A., Finizia, C., et al.[2023]

A quality improvement initiative at the Center for Cancer Care tracked adverse outcomes in 91 patients receiving radiotherapy, revealing that 54.9% experienced treatment-related toxicity and 21.1% died during or shortly after treatment.

The study found that advanced age was linked to poorer overall and disease-free survival, indicating that healthcare providers should pay special attention to elderly patients undergoing radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality improvement program in radiation oncology: understanding patient hospitalizations, treatment breaks, and weight loss in patients receiving radiotherapy. Chowdhry, V., Jangro, P., Goldberg, S., et al.[2019]

The workshop highlighted the potential of using very low dose human studies (microdoses) to assess drug candidates earlier in the development process, which could improve the selection of effective drugs while ensuring volunteer safety.

Incorporating advanced techniques like accelerator mass spectrometry (AMS) and positron emission tomography (PET) in these early human studies could provide valuable data on how drugs are processed in the body, potentially reducing reliance on animal testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early microdose drug studies in human volunteers can minimise animal testing: Proceedings of a workshop organised by Volunteers in Research and Testing. Combes, RD., Berridge, T., Connelly, J., et al.[2019]

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Pending the results from Part 1, healthy volunteers will be administered AFA-281 for 14 to 21 consecutive days in 3 cohorts. At scheduled intervals after dosing ...

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Researchers will compare AFA-281 to a placebo (a look-alike substance that contains no drug) to see if AFA-281 works to treat chronic low back and leg pain.

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Clinical Phase I trials on an IND single molecule ... - NIH RePORTER

AFA-281 produces significant analgesia and reduction of brain microglia activation in a neuropathic pain model of spared nerve injury (SNI) in rats. GLP safety ...

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Based on pharmacokinetic and pharmacodynamic (PK/PD) studies, AFA-281 has shown an excellent oral bioavailability (70% in rats and 92% in dogs), acceptable t1/2 ...

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A Study of the Safety and Exploratory Efficacy of Oral AFA-281 ...

This study will evaluate the safety and exploratory efficacy of AFA-281 in ... Biphasic alcohol effects scale and profile of negative mood states. Time ...