Phase 2a Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of VENT-03 in Adults with Active Cutaneous Lupus Erythematosus
- Trial ID
- 2024-520098-12-00
- Protocol
- VENT-03-201
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the effect of **VENT-03** on disease severity in adult participants with active **Cutaneous Lupus Erythematosus** (CLE), with or without Systemic Lupus Erythematosus. This is measured using the Cutaneous Lupus Erythematosus Disease Area and Severity Index activity (CLASI-A) score. The clinical relevance of this objective lies in its potential to provide insights into the efficacy of VENT-03 in reducing disease activity, which could lead to improved management and outcomes for patients with CLE.
Secondary objectives include:
- Evaluating the safety and tolerability of VENT-03 administered at 300 mg once daily compared to placebo.
- Assessing the pharmacodynamics (PD) of VENT-03, as measured by Myxovirus-resistant protein A (MXA) immunostaining in lesional skin biopsy.
- Evaluating the pharmacokinetics (PK) of VENT-03 in plasma.
Participants
The clinical trial involves a total of **10 participants** diagnosed with **Cutaneous Lupus Erythematosus**. The study population comprises both male and female subjects, aged between **18 to 70 years**, with a body weight ranging from **40 to 110 kg**. Participants were selected based on their ability to provide written informed consent and their reliability and willingness to adhere to study procedures. The trial does not include a vulnerable population. Participants of childbearing potential and those who can produce sperm are required to use highly effective contraception methods during and after the trial period. The study does not specify any particular lifestyle considerations such as diet or physical activity. The sponsor has not provided additional information regarding the general health status of the participants.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** Phase 2a study with an open-label extension, aimed at evaluating the efficacy and safety of VENT-03 in adult participants with active **cutaneous lupus erythematosus**, with or without systemic lupus erythematosus. The trial will assess the effect of VENT-03 on disease severity, as measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index activity (CLASI-A) score. The primary endpoint is the change from baseline in the CLASI-A score on Day 28, while secondary endpoints include treatment-emergent adverse events, vital signs, electrocardiogram, physical examination, safety laboratory assessments, change from baseline in MXA immunostaining in lesional skin biopsy, and plasma concentrations and pharmacokinetic parameters of VENT-03.
The trial is expected to commence recruitment on September 1, 2025, and conclude by August 14, 2026. Participants will be involved in the study for a maximum treatment period of one month, with the study drug administered orally in tablet form. The sequence of study visits includes an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess final outcomes. Participants will be required to meet specific inclusion criteria, such as being between 18 to 70 years of age, having a body weight within 40 to 110 kg, and providing written informed consent. They must also agree to use highly effective contraception methods if of childbearing potential or capable of producing sperm.
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 not classified as low intervention, and the investigational product, VENT-03, is a chemically derived tablet. The placebo tablets are identical in appearance to the VENT-03 tablets and are composed of excipients found in the VENT-03 formulation. The study is conducted under the sponsorship of Ventus Therapeutics U.S. Inc., with the investigational medicinal product authorized for use in the trial.
Treatment
The clinical trial involves the administration of **VENT-03**, an experimental medication developed by Ventus Therapeutics U.S. Inc. **VENT-03** is formulated as a tablet and is intended for oral administration. The active substance in **VENT-03** is of chemical origin, and the medication is not a pediatric formulation. The trial aims to evaluate the efficacy and safety of **VENT-03** in adult participants with active cutaneous lupus erythematosus, with or without systemic lupus erythematosus. The dosage and frequency of administration are determined by the study protocol, with a maximum treatment period of one unit of time as specified in the trial documentation. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.
The study also includes a placebo control group. The placebo tablets are composed of excipients identical to those found in **VENT-03** tablets, ensuring that they are indistinguishable from the active medication in appearance. The placebo serves as a comparator treatment to assess the efficacy of **VENT-03** in a double-blind manner. The placebo tablets are administered orally, following the same dosing schedule as the experimental medication. This design allows for a rigorous evaluation of the treatment effect while maintaining the integrity of the study's blinding process.
Efficacy
The efficacy of VENT-03 in the treatment of **Cutaneous Lupus Erythematosus** will be assessed through a multicenter, randomized, double-blind, placebo-controlled, Phase 2a study. The primary endpoint for evaluating efficacy is the change from baseline in the Cutaneous Lupus Erythematosus Disease Area and Severity Index activity (CLASI-A) score on Day 28. This score is a validated measure used to assess disease severity in patients with cutaneous lupus erythematosus.
Secondary endpoints include the assessment of treatment-emergent adverse events (TEAEs), vital signs, electrocardiogram (ECG) results, physical examination findings, and safety laboratory assessments. Additionally, changes from baseline in MXA immunostaining in lesional skin biopsy will be evaluated, along with plasma concentrations and pharmacokinetic (PK) parameters of VENT-03. These assessments will provide a comprehensive evaluation of both the efficacy and safety of the investigational product.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or female participants of age 18 to 80 years, inclusive.
- Body weight within the range of 40 to 110 kg (88 to 242 lbs), (inclusive).
- Has provided written informed consent
- Participants of childbearing potential, participants who are not post-menopausal or surgically sterile must agree to use a highly effective method of contraception from ≥ 30 days prior to dosing through 30 days after the last IMP administration.
- Participants (or partners of POCBP) who can produce sperm must use a highly effective methods of contraception from ≥ 30 days prior to dosing through 90 days after the last IMP administration. Participants who can produce sperm must agree to not donate sperm through 90 days after the last IMP administration.*
- Participant is, per the investigator’s assessment, reliable and willing to be available for the duration of the study and is willing and able to perform and follow all study procedures and requirements.
- Cutaneous lupus at Screening
Exclusion Criteria
- Has any clinical condition or clinically significant abnormality at Screening that in the opinion of the Investigator would interfere with evaluation of the IMP, affect participant safety, or interpretation of study results
- Use of any restricted medications within the stated washout period
- Intra-articular, intramuscular or IV glucocorticosteroids within 6 weeks prior to Day 1
- Any live or attenuated vaccine within 8 weeks prior to signing the ICF or Bacillus Calmette-Guerin (BCG) vaccine within 1 year prior to Day 1. Administration of killed vaccines is acceptable;
- Blood transfusion within 4 weeks prior to Day1.
- Patient is taking a strong inhibitor or inducer of cytochrome P450 Patient is taking a strong inhibitor of the BCRP transporter Patient is taking a narrow therapeutic index medication that is a substrate of CYP2C8 or CYP2C9 Patient is taking a narrow therapeutic index medication that is a substrate of the BCRP, OAT1, OAT3, OATP1B1 or OATP1B3 transporters
- Has drug induced lupus, rather than “idiopathic” lupus.
- History of, or current, inflammatory joint or skin disease other than SLE and cutaneous lupus, including other autoimmune that, in the opinion of the Investigator, could interfere with disease activity assessments
- Diagnosis of mixed connective tissue disease or any history of overlap syndromes of SLE or systemic sclerosis (SSc) within 1 year prior to signing the ICF
- History of, or current diagnosis of, a clinically significant non SLE-related vasculitis syndrome. Vasculitis due to SLE is permissible.
- Active severe or unstable neuropsychiatric SLE
- Participant is involved with the conduct of the study, or is an employee, or immediate family member of individuals involved with the conduct of the study.
- Hospitalization for a severe lupus flare in the past 3 months, active severe SLE-driven renal disease
- History or current diagnosis of anti-phospholipid syndrome
- History of any non-lupus disease that has required treatment with oral or parenteral corticosteroids for more than a total of 2 weeks within the last 24 weeks prior to Day 1.
- Known history of a primary (HIV)
- Latent or active tuberculosis (TB)
- Confirmed positive test on hepatitis B serology
- Positive test for hepatitis C antibody
- History of any severe herpes infection
- Herpes zoster
- Opportunistic infection requiring hospitalization.
- Had a major surgery within 8 weeks before Day 1 or elective major surgery planned during thestudy period.
- Cancer screening result suspicious for malignancy or history of cancer within 2 years prior to Day 1
- Pregnant or nursing.
- Known hypersensitivity to any components of the VENT-03 formulation.
- Poor venous access.
- Currently enrolled in any other interventional clinical trial involving an investigational product within 30 days or 5 half-lives (whichever is longer) prior to dosing or enrolled in any other type of medical research.
- History of alcohol or substance use disorder in the 12 months prior to Screening or positive drug test at Screening.
- Regular use of > 1 nonsteroidal anti-inflammatory drug (NSAID) within 2 weeks prior to Day 1 or receipt of fluctuating doses of a NSAID within 2 weeks prior to Day 1.
- Any clinically significant abnormal ECG result at Screening that could increase risk of participation in the study.
- Moderate or severe liver impairment as classified by the Child-Pugh criteria (categories B and C).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Recruiting | 01 Sept 2025 | 2 |
 Czechia | Not Recruiting | 01 Sept 2025 | 1 |
 France | Recruiting | 01 Sept 2025 | 1 |
 Hungary | Recruiting | 01 Sept 2025 | 1 |
 Poland | Recruiting | 01 Sept 2025 | 7 |
 Spain | Recruiting | 01 Sept 2025 | 1 |
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 tablets are composed of excipients found in VENT-03 tablets. Placebo tablets are identical to VENT-03 tablets. | Placebo | N/A | — | — | — | N/A |
VENT-03 | Test | TABLET | ORAL | 0.00 | 1 | PRD12290826 |