AC-1101 Gel for Granuloma Annulare

Overseen By Nicole Olszewski, study coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: TWi Biotechnology, Inc.

Must not be taking: Biologics, Immunosuppressives

Disqualifiers: Active malignancy, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of a new topical gel, AC-1101, for treating Granuloma Annulare, a skin condition that causes red, ring-shaped bumps. Participants will apply the gel for four weeks, followed by a two-week observation period without treatment. Eligible individuals should have had active Granuloma Annulare for at least two years with stable symptoms and have previously struggled with or not tolerated other treatments like antibiotics or topical steroids.

As a Phase 1 trial, participants will be among the first to receive this new treatment, helping researchers understand how it works in people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that prescription medications should not be used within 14 days before the first dose, except for ongoing treatments for existing conditions as judged by the Investigator.

Is there any evidence suggesting that AC-1101 gel is likely to be safe for humans?

Research has shown that AC-1101, a topical gel, has undergone previous testing on people. In these early tests, most participants did not experience serious side effects, indicating that the treatment was generally safe. However, this study remains in its early stages. Initial trials primarily assess safety before evaluating effectiveness. Since AC-1101 is applied to the skin, it typically causes fewer side effects than oral medications. Overall, early results suggest that AC-1101 is safe for most individuals. As with any treatment, discussing potential risks with the medical team conducting the trial is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for granuloma annulare, which often include corticosteroids or systemic medications, AC-1101 is a topical gel designed to be applied directly to the skin. This method of delivery targets the affected area specifically, potentially minimizing systemic side effects associated with oral medications. Researchers are excited because AC-1101 might offer a more localized, safer, and user-friendly alternative for patients, with the gel formulation providing a novel approach in managing this skin condition.

What evidence suggests that AC-1101 gel might be an effective treatment for Granuloma Annulare?

Research suggests that AC-1101, the treatment under study in this trial, might help treat granuloma annulare, a skin condition. Earlier studies found that AC-1101 was well-tolerated and showed some signs of effectiveness. This treatment targets inflammatory skin diseases, such as granuloma annulare, offering hope to those affected. Although the research remains in its early stages, these initial findings indicate that AC-1101 could help reduce granuloma annulare symptoms. More studies are needed to confirm these results. ^{1 3 5 6 7}

Who Is on the Research Team?

William Damsky, M.D., Ph.D.

Principal Investigator

Yale Department of Dermatology

Are You a Good Fit for This Trial?

Inclusion Criteria

Adequate organ function and marrow function meaured at screening (Visit 1) and enrollment (Visit 2) as defined below: Hemoglobin ≥ 12.0 g/dL for male and 10.5 g/dL for female; Absolute neutrophil count ≥ 1,300 /µL; Absolute lymphocytes: 1.0-4.0 x 109/L (1000-4000 cells/mm3) as the reference range; Platelets ≥ 75,000/µL; Total bilirubin ≤ 1.5 x upper normal limit; AST(SGOT)/ALT(SGPT) ≤ 2.5 x upper normal limit; eGFR ≥ 60mL/min/1.73m2

Patients with 1-20% BSA of active Granuloma Annulare lesions will be enrolled.

Other subtypes of GA, such as linear, perforating, and subcutaneous will be excluded from the study. If there is suspicion that GA is medication-induced, the patient will not be enrolled. GA in association with human immunodeficiency virus (HIV) or malignancy will be excluded.

Exclusion Criteria

History of allergic reactions to tofacitinib or other related drugs, or to any excipient in the formulation.

Women of childbearing potential who are unable or unwilling to use birth control (oral pills, rings or patches are not permitted) while taking the medication.

Pregnant or breast-feeding women.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Treatment

Participants receive AC-1101 topical gel for 4 weeks to assess safety, tolerability, and efficacy

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• AC-1101

How Is the Trial Designed?

Group I: Patients with Granuloma Annulare Experimental Treatment 1 Intervention

4-week treatment and 2-week follow-up period (without treatment)

Who Is Running the Clinical Trial?

TWi Biotechnology, Inc.

Lead Sponsor

Trials

10

Recruited

690+

Published Research Related to This Trial

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 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 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 first-in-human clinical trial of BIA 10-2474 resulted in serious adverse events for 6 healthy volunteers, including 1 death, highlighting the heightened risks associated with novel investigational drugs transitioning from animal studies to human trials.

The symposium emphasized the need for careful planning and communication in clinical trials to minimize risks to participants, suggesting that a complex matrix of factors must be considered to ensure safety and integrity in first-in-human studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety in FIH Trials: A Summary of the Symposium "Fatal Drug Trial in Phase 1: Understanding Risk, Subject Safety, Timelines, and Cost". Greenberg, HE., van Iersel, MT., Westrick, ML., et al.[2020]

In a review of 24 Phase I studies involving 430 healthy male volunteers over 5 years, the overall incidence of adverse events was 13.5%, with a higher rate for active drug treatments (15.3%) compared to placebo (7.4%).

Severe adverse events occurred in 20 cases (0.36%), but there were no deaths or life-threatening incidents, indicating that while adverse events are common, they are generally not severe in Phase I trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in phase one studies: a study in 430 healthy volunteers. Sibille, M., Deigat, N., Olagnier, V., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05580042

Study to Evaluate the Safety and Tolerability of AC-1101 ... Study AC-1101-GA-001 is an early phase open-label study with a 4-week treatment and 2-week follow-up period (without treatment) to assess the safety, ...

2. withpower.com withpower.com/trial/phase-1-granuloma-8-2022-f6469

Study to Evaluate the Safety and Tolerability of AC-1101 ... In a review of 24 Phase I studies involving 430 healthy male volunteers over 5 years, the overall incidence of adverse events was 13.5%, with a higher rate for ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10500476/

Molecularly Targeted Therapies for Inflammatory ... To date, two patients with GA treated with compounded topical 2% tofacitinib ointment showed significant benefit after 12 or 15 weeks of twice-daily application ...

4. jidinnovations.org jidinnovations.org/article/S2667-0267(23)00045-0/pdf

Molecularly Targeted Therapies for Inflammatory ... Inflammatory cutaneous granulomatous diseases, including granuloma annulare, cutaneous sarcoidosis, and necrobiosis lipoidica, are distinct diseases unified.

5. elischolar.library.yale.edu elischolar.library.yale.edu/cgi/viewcontent.cgi?article=4240&context=ymtdl

Janus Kinase Inhibition In Granuloma Annulare - EliScholar Further results from this trial will clarify the efficacy of abrocitinib over 6 months of use. AC-1101 was well-tolerated and demonstrated evidence of efficacy.

6. ctv.veeva.com ctv.veeva.com/study/study-to-evaluate-the-safety-and-tolerability-of-ac-1101-topical-gel-in-patients-with-granuloma-annu

Study to Evaluate the Safety and Tolerability of AC-1101 ... Patients with 1-20% BSA of active Granuloma Annulare lesions will be enrolled. Duration of active GA must be at least two years with no ...

7. sigma.larvol.com sigma.larvol.com/product.php?e1=1022801&tab=ott&sourcepg=TZP

tofacitinib citrate topical gel (AC-1101) Trials NCT05580042: Study to Evaluate the Safety and Tolerability of AC-1101 Topical Gel in Patients with Granuloma Annulare. Completed. 1.