Efficacy and Safety Evaluation of AVTX-009 in Moderate to Severe Hidradenitis Suppurativa: A Phase 2 Randomized, Double-blind, Placebo-controlled Study
- Trial ID
- 2024-514562-40-00
- Protocol
- AVTX-009-HS-201
- Sponsor
- Avalo Therapeutics Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of AVTX-009 compared to placebo in the treatment of subjects with moderate to severe **hidradenitis suppurativa** (HS). This is clinically relevant as hidradenitis suppurativa is a chronic inflammatory skin condition that significantly impacts patients' quality of life, and effective treatments are limited.
Secondary objectives include:
- Assessing the **safety** and tolerability of AVTX-009 in subjects with moderate to severe HS.
- Evaluating the efficacy of AVTX-009 versus placebo using additional outcome measures for the treatment of subjects with moderate to severe HS.
- Evaluating the **immunogenicity** of AVTX-009 in subjects with moderate to severe HS.
Participants
The clinical trial for evaluating the efficacy of AVTX-009 versus placebo in the treatment of **hidradenitis suppurativa (HS)** involves a total of 54 participants. The study population includes both male and female subjects, aged 18 years and older, who have been diagnosed with moderate to severe HS. Participants were selected based on their ability to understand and provide informed consent, as well as their compliance with study requirements, including the use of an electronic diary. The trial does not include vulnerable populations. Key lifestyle considerations include the requirement for non-pregnant, non-lactating female subjects of childbearing potential and their partners to use highly effective contraception methods during the study and for a specified period after the last dose. Participants must also agree not to donate eggs or sperm during the study and for a period following the study drug administration. The selection criteria ensure that subjects have no history of tuberculosis and meet specific health standards, as confirmed by medical history and screening tests.
Plans and Procedures
The clinical trial is a **Phase 2**, randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy and safety of **AVTX-009** in patients with moderate to severe **hidradenitis suppurativa**. The trial will involve the administration of AVTX-009, a solution for injection, and a placebo, both delivered via subcutaneous injection. The study aims to assess the primary endpoint of achieving Hidradenitis Suppurativa Clinical Response 75 (HiSCR75) at Week 16, defined as at least a 75% reduction in the total abscess and inflammatory nodule count, with no increase in abscess or draining fistula count relative to baseline. Secondary endpoints include the incidence of adverse events, changes in vital signs, and various measures of clinical response and symptom improvement.
The trial is expected to commence recruitment on February 12, 2025, and conclude by July 24, 2026. Participants will be involved in the study for a maximum treatment period of 16 weeks. The sequence of study visits includes an initial screening visit to confirm eligibility based on criteria such as age, disease severity, and tuberculosis screening. Following the screening, eligible participants will undergo a baseline visit where they will be randomized to receive either AVTX-009 or placebo. Subsequent follow-up visits will occur at regular intervals to monitor safety, efficacy, and any adverse events. The end-of-study visit will mark the completion of the participant's involvement, where final assessments will be conducted.
Participants are expected to adhere to the study protocol, including the use of contraception for eligible females and males, and agree not to donate reproductive cells during and after the study period. Conditions that may lead to early termination from the study include non-compliance with study procedures, withdrawal of consent, or the occurrence of significant adverse events. The trial is structured to ensure rigorous assessment of AVTX-009's therapeutic potential while maintaining participant safety and data integrity.
Treatment
The clinical trial involves the administration of **AVTX-009**, an investigational medication formulated as a **solution for injection**. The active substance, AVTX-009, is a protein-based compound developed by Avalo Therapeutics. The medication is administered via **subcutaneous injection**. The dosing regimen includes a maximum daily dose of 600 mg, with a total maximum dose of 1500 mg over a treatment period of up to 16 weeks. The trial aims to assess the efficacy and safety of AVTX-009 in patients with moderate to severe **hidradenitis suppurativa**.
In addition to the experimental treatment, a **placebo** is utilized as a comparator in this double-blind, placebo-controlled study. The placebo is designed to match the pharmaceutical form of AVTX-009, ensuring blinding is maintained throughout the trial. The placebo is administered following the same route and frequency as the active treatment, allowing for a direct comparison of outcomes between the treatment and control groups. Compliance with the dosing schedule is monitored to ensure adherence to the protocol and to accurately assess the efficacy of the investigational product.
Efficacy
The efficacy of AVTX-009 in the treatment of moderate to severe **Hidradenitis Suppurativa** will be assessed through a series of primary and secondary endpoints. The primary endpoint is the proportion of subjects achieving Hidradenitis Suppurativa Clinical Response 75 (HiSCR75) at Week 16. This is defined as at least a 75% reduction in the total abscess and inflammatory nodule (AN) count, with no increase in abscess count and no increase in draining fistula count relative to Baseline.
Secondary endpoints include the incidence of adverse events, changes from Baseline in vital signs, physical examinations, and clinical laboratory tests. Additionally, the proportion of subjects achieving HiSCR50 and HiSCR90 by visit will be evaluated, defined as at least a 50% and 90% reduction in the total AN count, respectively, with no increase in abscess or draining fistula counts relative to Baseline. Other secondary measures include changes from Baseline in the International HS Severity Score System (IHS4), AN count, and draining fistula count. The percentage of subjects achieving at least a 30% reduction and at least a 1-unit reduction from Baseline on a Numerical Rating Scale (NRS) in Patient’s Global Assessment of Skin Pain (PGA Skin Pain) among subjects with Baseline NRS ≥3 (NRS30) will also be assessed. Furthermore, the percentage of subjects with flares, defined as a ≥25% increase in AN count plus an increase of ≥2 in AN count compared to Baseline, and the incidence of AVTX-009 anti-drug antibodies (ADA) at specified timepoints will be monitored.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Subject is ≥ 18 years of age at the time of informed consent.
- Subject can understand and provide written informed consent to participate in this study, agrees to comply with the requirements of the study, is able to read and understand study questionnaires, and has the ability to utilize an electronic diary.
- Subject has signs and symptoms of HS for at least 6 months prior to Screening as determined by the Investigator (e.g., through review of medical history, interview of the subject).
- Subject’s HS is considered moderate or severe defined as: -A total of at least 5 inflammatory lesions, i.e., an AN count of ≥ 5 AND - HS inflammatory lesions in at least 2 distinct anatomic areas, at least one of which is Hurley Stage 2 or 3.
- Subject is considered eligible according to the following tuberculosis (TB) screening criteria: -Has no history of latent or active TB, is not receiving concurrent treatment for TB, and does not show signs and/or symptoms of TB upon medical history review and/or physical examination at Screening. - Has a negative QuantiFERON-TB Gold test result or a negative tuberculin skin test. - Has a negative chest radiograph (posterior-anterior view) at Screening, or a negative chest radiograph/computed tomography (CT) taken within 3 months before Screening
- Non-pregnant, non-lactating female subjects of childbearing potential who are heterosexually active and female sexual partners of childbearing potential of non-sterile male subjects must be using a highly effective method of contraception for 28 days prior to Baseline and agree to use a highly effective method of contraception during the treatment period and for 5 half-lives (14 weeks) following the last dose of study drug.
- Subjects must agree not to donate eggs (ova, oocytes) or sperm for the purposes of assisted reproduction during participation in the study and for 5 half-lives (14 weeks) after the last study drug administration.
Exclusion Criteria
- Subject has a draining fistula count of ≥ 20.
- Subject has another active skin inflammatory condition or infection (viral, bacterial, or fungal) which could interfere with the assessment of HS.
- Subject has another active ongoing inflammatory disease (other than HS) that requires treatment with a prohibited medication.
- Subject has a history of chronic or recurrent infectious disease, including but not limited to chronic renal infection, chronic lung infection, recurrent urinary tract infection, or open, draining or infected skin wounds or ulcers (not related to HS).
- Subject has been hospitalized for an infection or received intravenous antibiotics for an infection during the 8 weeks prior to Screening.
- Subject has known or suspected immunosuppression, including but not limited to a history of invasive opportunistic infection or solid organ transplant (excluding corneal transplantation performed >3 months prior to Screening).
- Subject has a history of or laboratory evidence of human immunodeficiency virus (HIV) at Screening.
- Subject has a history of symptomatic herpes zoster within the 30 days prior to Screening.
- Subject has laboratory evidence of active or chronic Hepatitis B (HBV) as evidenced by: - A positive Hepatitis B surface antigen test, OR - A positive anti-Hepatitis B core antibody test, except in the circumstance of a negative HBV DNA PCR test, in which case the subject is permitted to enroll.
- Subject has a history of or laboratory evidence of Hepatitis C virus (HCV) (HCV antibody positive) at Screening except in the circumstance of a negative HCV RNA PCR test result.
- Subject has an active malignancy or lymphoproliferative disorder or a history thereof within the last 5 years, with the exception of resected non-melanoma (basal or squamous cell) skin cancer with no evidence of metastatic disease, or effectively managed cervical carcinoma in situ.
- Subject has severe, progressive and/or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac (New York Heart Association Grade ≥ 3), neurologic or immunosuppressive disease.
- Subject has had suicidal ideation or suicidal behavior within the previous 6 months or has severe depression as indicated by a PHQ-9 score of ≥ 20, or the subjects answers anything other than “Not at all” to Question #9 on the PHQ-9 questionnaire at Screening or Baseline.
- Subject has any other clinically significant acute or chronic medical condition(s) that, in the judgment of the Investigator, would preclude the use of a subcutaneous (SC) injection or the study drug that could compromise subject safety, limit the subject’s ability to complete the study, and/or confound the results or compromise the objectives of the study.
- Subject has had prior exposure to AVTX-009 (previously known as LY2189102 and FL-101) or prior therapy with an anti-IL-1 targeting agent.
- Subject has received a biologic immunosuppressive medication within 6 weeks or 5 half-lives, whichever is longer, of Baseline.
- Subject has received an immunosuppressive/immunomodulating medication within 28 days of Baseline.
- Subject has received any live, attenuated vaccine within 3 months of Baseline.
- Subject has received any other investigational agent within 5 half-lives (or 30 days for chemical agents, 8 weeks for biologic agents, whichever is longer) of Baseline
- Subject has used any topical therapy for HS within 14 days prior to the Baseline Visit, with the exception of OTC antiseptics if the subject has been on a stable regimen for at least 14 days prior to Baseline and no intent to change during the study.
- Subject has used any systemic therapies that may be effective for treating HS within 28 days prior to the Baseline Visit, with the exceptions listed in the Protocol.
- Subject has received intralesional injections, surgical intervention (other than incision and drainage) or other physical modalities (e.g., light, laser, radiofrequency) for treatment of HS within 28 days prior to the Baseline Visit.
- Subject has used opioid analgesics (including tramadol) within 14 days prior to Baseline, or it is anticipated that the subject will require opioid analgesics for any reason during the study period.
- Subject has any of the laboratory abnormalities listed in the Protocol (exclusion criteria point 24)
- Female subject who is pregnant or is breastfeeding and will not abstain from breastfeeding during participation in the study and for 14 weeks after the last dose of study drug.
- Subject has a history of clinically significant drug or alcohol abuse within the 12 months prior to Screening.
- Subject has a known or suspected intolerance or hypersensitivity to the study drug, other biologics, or closely related compounds, or any ingredients of the study drug(s).
- Subject for whom there is any concern on the part of the Investigator regarding the subject’s legal or mental incapacitation, the subject’s ability to understand the protocol or regarding the subject’s safety, compliance, or suitability with respect to his/her participation in the study. Notably, the following subjects are excluded in France: vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection, or who are unable to express their consent per article L.1121-8 of the French Public Health Code, not affiliated to a social security per article L.1121-8-1 of the French Public Health Code.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Not Recruiting | 12 Feb 2025 | 40 |
 Czechia | Not Recruiting | 12 Feb 2025 | 13 |
 France | Not Recruiting | 12 Feb 2025 | 18 |
 Germany | Not Recruiting | 12 Feb 2025 | 12 |
 Greece | Not Recruiting | 12 Feb 2025 | 42 |
 Italy | Not Recruiting | 12 Feb 2025 | 34 |
 Poland | Not Recruiting | 12 Feb 2025 | 59 |
 Slovakia | Not Recruiting | 12 Feb 2025 | 10 |
 Spain | Not Recruiting | 12 Feb 2025 | 15 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo to AVTX-009 | Placebo | N/A | — | — | — | N/A |
AVTX-009 | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS INJECTION | 600 | 16 | PRD11518304 |