Study to Evaluate the Safety and Tolerability of AC-1101 Topical Gel in Patients with Granuloma Annulare

NCT05580042 | Completed Phase 1 FDA Drug

• 1 other identifier: AC-1101-GA-001
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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, tolerability, and efficacy of AC-1101 gel in patients with Granuloma Annulare.

Conditions

Granuloma Annulare

Keywords

Tofacitinib Topical Gel 2%; AC-1101 gel

Outcome Measures

Primary Outcomes (7)

• Incidence and proportion of subjects with treatment emergent adverse events (TEAEs), AEs and serious adverse events (SAEs).

  Adverse events (AEs), Significant Adverse Events (SAEs), treatment emergent adverse events (TEAEs)

  Up to 6 weeks

• Number of subjects with abnormal vital signs

  Vital sign parameters will be analyzed including oral temperature, pulse rate, respiratory rate, and blood pressure.

  Up to 6 weeks

• Number of subjects with abnormal ECG

  ECGs will be obtained by using an automated ECG machine to measure PR, QRS, QT, and QTc intervals and calculates heart rate.

  Up to 6 weeks

• Number of subjects with abnormal hematology parameters

  Hematology parameters will be analyzed including platelet count, RBC count, hemoglobin, hematocrit, MCV, MCH, percent reticulocytes, WBC count, neutrophils, lymphocytes, monocytes, eosinophils and basophils.

  Up to 6 weeks

• Number of subjects with abnormal biochemistry parameters

  Biochemistry parameters will be analyzed including blood urea nitrogen (BUN), creatinine, glucose, phosphorus, calcium, phosphate, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, creatine phosphokinase (CPK), total bilirubin, direct bilirubin, total protein, albumin to gloulin ratio, globulin, lipase, and Hemoglobin A1C..

  Up to 6 weeks

• Number of subjects with abnormal urinalysis parameters

  Urinalysis parameters will be analyzed including specific gravity, urine creatinine, phosphate and pregnancy test..

  Up to 6 weeks

• Change in skin irritation using Dermal Rating Scale (DRS)

  This is a 0-4 rating with 0 representing the best.

  Up to 4 weeks

Secondary Outcomes (6)

• Plasma concentration of AC-1101

  Day 1, Day 14, Day 42:Pre-dose; Day 28: Pre-dose, 2 through 24 hours post-dose

• Area under the plasma concentration-time curve from time 0 to last time of quantifiable concentration (AUC[0-t]) of AC-1101

  Day 1, Day 14, Day 42:Pre-dose; Day 28: Pre-dose, 2 through 24 hours post-dose

• Area under the plasma concentration-time curve from time 0 to extrapolated to infinity (AUC[0-infinity]) of AC-1101

  Day 1, Day 14, Day 42:Pre-dose; Day 28: Pre-dose, 2 through 24 hours post-dose

• Maximum observed plasma drug concentration (Cmax) of AC-1101

  Day 1, Day 14, Day 42:Pre-dose; Day 28: Pre-dose, 2 through 24 hours post-dose

• Time to maximum observed plasma drug concentration (Tmax) of AC-1101

  Day 1, Day 14, Day 42:Pre-dose; Day 28: Pre-dose, 2 through 24 hours post-dose

Other Outcomes (7)

• Change in Patient Global Impression of Change in GA (PGIC-GA)

  Up to 4 weeks

• Change in Dermatology Life Quality Index (DLQI)

  Up to 4 weeks

• Change in Skindex-16

  Up to 4 weeks

Study Arms (1)

Patients with Granuloma Annulare

EXPERIMENTAL

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

Drug: AC-1101

Interventions

AC-1101 DRUG

For each patient, once daily (QD)

Also known as: Tofacitinib Topical Gel 2%, AC-1101 gel

Patients with Granuloma Annulare

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients 18 years of age or older, male or female, will be enrolled.
• Diagnosis of granuloma annulare with supportive skin biopsy (diagnostic shave biopsy or punch biopsy) or historical biopsy (a provided report would be sufficient and would not require to repeat the diagnostic biopsy). A biopsy at any point is sufficient. If a diagnostic biopsy has never been performed, one will be performed prior to enrollment in the study. Patients with both localized and generalized GA will be enrolled in the proposed study.
• 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.
• 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 significant change in size or number of lesions in the 6 months prior to treatment as supported by a combination of record review and history/patient interview.
• Patients who might be recalcitrant to or intolerant of conventional treatment, such as antibiotics (e.g., doxycycline or minocycline), triple antibiotic therapy of rifampin, ofloxacin, and minocycline, topical corticosteroids, topical calcineurin inhibitors, intralesional/intramuscular corticosteroid and/or phototherapy.
• 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
• Females of childbearing potential who are sexually active with a male partner must be willing to use one of the following acceptable contraceptive methods throughout the study and for 30 days after the last study drug administration.

You may not qualify if:

• Patients with active malignancy will not be permitted to enroll in the proposed study. Patients with a history of treated nonmelanoma skin cancer will be eligible to enroll.
• Patients under treatment with biologics or other systemic immunosuppressive medications (e.g., methotrexate (MTX), mycophenolate) within the last 3 months.
• Presence of any clinically significant abnormality at physical examination, clinically significant abnormal laboratory assessment or positive test for hepatitis B (HBs-Ag), hepatitis C (HCV-Ab), or HIV found during medical screening.
• History of allergic reactions to tofacitinib or other related drugs, or to any excipient in the formulation.
• Positive pregnancy test at screening. If a woman becomes pregnant during the study, she will stop the study medication and be removed from the study. She will be urged to follow up with her Primary Care Physician or obstetrician-gynecologist. The study doctors will ask to follow the pregnancy to its outcome.
• 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.
• Current active smokers.
• Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing, or concomitant participation in an investigational study involving drug or device administration.
• History of active tuberculosis or exposure to endemic areas within 8 weeks prior to QuantiFERON®-TB testing performed at screening.
• Positive QuantiFERON®-TB indicating possible tuberculosis infection.
• Immunization with a live attenuated vaccine within 1 month prior to dosing or planned vaccination during the study.
• History of clinically significant opportunistic infection, e.g., invasive fungal infections or pneumocystis pneumonia.
• Serious local infection, e.g., cellulitis, abscess, or systemic infection, e.g., septicemia, within 3 months prior to screening.
• Use of medications for the timeframes specified below, with the exception of medications exempted by the Investigator on a case-by-case basis, such as Acetaminophen (2g in 24-hour period) because they are judged unlikely to affect the PK profile of the study drug or subject safety:

Sponsors & Collaborators

• TWi Biotechnology, Inc.: lead

Study Sites (1)

Yale Center for Clinical Investigation

New Haven, Connecticut, 06519, United States

Location

MeSH Terms

Conditions

Granuloma Annulare

Condition Hierarchy (Ancestors)

Necrobiotic Disorders; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Granuloma; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• William Damsky, M.D., Ph.D.

  Yale Department of Dermatology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: patients with Granuloma Annulare

Study Record Dates

• First Submitted: October 2, 2022
• First Posted: October 14, 2022
• Study Start: October 3, 2022
• Primary Completion: November 15, 2023
• Study Completion: November 15, 2023
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)