A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study With an Open-Label Extension Evaluating the Efficacy and Safety of VENT-03 in Adult Participants With Active Cutaneous Lupus Erythematosus With or Without Systemic Lupus Erythematosus

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ventus Therapeutics U.S. Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

16 Feb 2026 → ongoing

Decision date (initial)

2025-08-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ventus Therapeutics, U.S., Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenetic, Safety

Evaluate the effect of VENT-03 on the interferon (IFN) gene signature in the skin

Secondary objectives 1

1. Evaluate the effect of VENT-03 on disease severity, evaluate safety and tolerability of VENT-03 administered at 300 mg once daily (QD) compared to placebo Evaluate the pharmacodynamics (PD) of VENT-03 as measured by Myxovirus-resistant protein A (MXA) immunostaining in lesional skin biopsy Evaluate the pharmacokinetics (PK) of VENT-03 in plasma

Conditions and MedDRA coding

Cutaneous Lupus Erythematosus

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Male or female participants of age 18 to 80 years, inclusive.
2. 2. Body weight within the range of 40 to 110 kg (88 to 242 lbs), (inclusive).
3. 3. Has provided written informed consent
4. 4. 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.
5. 5. 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.*
6. 6. 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.
7. 7. Cutaneous lupus at Screening

Exclusion criteria 32

1. 1. 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
2. 12. Use of any restricted medications within the stated washout period
3. 13. Intra-articular, intramuscular or IV glucocorticosteroids within 6 weeks prior to Day 1
4. 14. 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;
5. 15. Blood transfusion within 4 weeks prior to Day1.
6. 16. 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
7. 17. Has drug induced lupus, rather than “idiopathic” lupus.
8. 18. 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
9. 19. 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
10. 20. History of, or current diagnosis of, a clinically significant non SLE-related vasculitis syndrome. Vasculitis due to SLE is permissible.
11. 21. Active severe or unstable neuropsychiatric SLE
12. 2. 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.
13. 22. Hospitalization for a severe lupus flare in the past 3 months, active severe SLE-driven renal disease
14. 23. History or current diagnosis of anti-phospholipid syndrome
15. 24. 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.
16. 25. Known history of a primary (HIV)
17. 26. Latent or active tuberculosis (TB)
18. 27. Confirmed positive test on hepatitis B serology
19. 28. Positive test for hepatitis C antibody
20. 29. History of any severe herpes infection
21. 30. Herpes zoster
22. 31. Opportunistic infection requiring hospitalization.
23. 3. Had a major surgery within 8 weeks before Day 1 or elective major surgery planned during thestudy period.
24. 32. Cancer screening result suspicious for malignancy or history of cancer within 2 years prior to Day 1
25. 4. Pregnant or nursing.
26. 7. Known hypersensitivity to any components of the VENT-03 formulation.
27. 8. Poor venous access.
28. 9. 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.
29. 10. History of alcohol or substance use disorder in the 12 months prior to Screening or positive drug test at Screening.
30. 11. 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.
31. 5. Any clinically significant abnormal ECG result at Screening that could increase risk of participation in the study.
32. 6. Moderate or severe liver impairment as classified by the Child-Pugh criteria (categories B and C).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change from baseline in the IFN gene signature in the skin at Day 28

Secondary endpoints 1

1. Treatment-emergent adverse events (TEAEs), vital signs, electrocardiogram (ECG), physical examination, and safety laboratory assessments Change from baseline in MXA immunostaining in lesional skin biopsy Plasma concentrations and PK parameters of VENT-03

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ventus Therapeutics U.S. Inc.

Sponsor organisation

Ventus Therapeutics U.S. Inc.

Address

100 Beaver Street Suite 201

City

Waltham

Postcode

02453-8400

Country

United States

Scientific contact point

Organisation

Ventus Therapeutics U.S. Inc.

Contact name

Amy Archer, MD

Public contact point

Organisation

Ventus Therapeutics U.S. Inc.

Contact name

Amy Archer, MD

Third parties 12

Locations

6 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 117 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications