Phase 2, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of AVTX-009 in Patients with Moderate to Severe Hidradenitis Suppurativa (LOTUS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Avalo Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

13 Mar 2025 → 18 Mar 2026

Decision date (initial)

2025-02-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of AVTX-009 versus placebo for the treatment of subjects with moderate to severe hidradenitis suppurativa (HS)

Secondary objectives 3

1. To assess the safety and tolerability of AVTX-009 in subjects with moderate to severe HS
2. To assess the efficacy of AVTX-009 versus placebo using additional outcome measures for the treatment of subjects with moderate to severe HS
3. To evaluate the immunogenicity of AVTX-009 in subjects with moderate to severe HS

Conditions and MedDRA coding

Hidradenitis suppurativa (HS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Subject is ≥ 18 years of age at the time of informed consent.
2. 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.
3. 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).
4. 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.
5. 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
6. 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.
7. 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 28

1. Subject has a draining fistula count of ≥ 20.
2. Subject has another active skin inflammatory condition or infection (viral, bacterial, or fungal) which could interfere with the assessment of HS.
3. Subject has another active ongoing inflammatory disease (other than HS) that requires treatment with a prohibited medication.
4. 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).
5. Subject has been hospitalized for an infection or received intravenous antibiotics for an infection during the 8 weeks prior to Screening.
6. 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).
7. Subject has a history of or laboratory evidence of human immunodeficiency virus (HIV) at Screening.
8. Subject has a history of symptomatic herpes zoster within the 30 days prior to Screening.
9. 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.
10. 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.
11. 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.
12. Subject has severe, progressive and/or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac (New York Heart Association Grade ≥ 3), neurologic or immunosuppressive disease.
13. 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.
14. 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.
15. 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.
16. Subject has received a biologic immunosuppressive medication within 6 weeks or 5 half-lives, whichever is longer, of Baseline.
17. Subject has received an immunosuppressive/immunomodulating medication within 28 days of Baseline.
18. Subject has received any live, attenuated vaccine within 3 months of Baseline.
19. 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
20. 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.
21. 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.
22. 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.
23. 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.
24. Subject has any of the laboratory abnormalities listed in the Protocol (exclusion criteria point 24)
25. 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.
26. Subject has a history of clinically significant drug or alcohol abuse within the 12 months prior to Screening.
27. 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).
28. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of subjects achieving Hidradenitis suppurativa Clinical Response 75 (HiSCR75) at Week 16 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 9

1. Incidence of adverse events (AEs), and changes from Baseline in vital signs, physical examinations, and clinical laboratory tests
2. The proportion of subjects achieving HiSCR50 by visit defined as: - At least a 50% reduction in the total AN count, with no increase in abscess count and no increase in draining fistula count relative to Baseline
3. The proportion of subjects achieving HiSCR90 by visit defined as: - At least a 90% reduction in the total AN count, with no increase in abscess count and no increase in draining fistula count relative to Baseline
4. Change from Baseline in International HS Severity Score System (IHS4)
5. Change from Baseline in AN count
6. Change from Baseline in draining fistula count
7. 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). NRS30 is based on worst skin pain in a 24-hour recall period (maximal daily pain)
8. Percentage of subjects with flares defined as ≥25% increase in AN count plus an increase of ≥2 in AN count compared to Baseline
9. Incidence of AVTX-009 anti-drug antibodies (ADA) at specified timepoints

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Avalo Therapeutics Inc.

Sponsor organisation

Avalo Therapeutics Inc.

Address

1500 Liberty Ridge Drive Suite 321

City

Chesterbrook

Postcode

19087-5574

Country

United States

Scientific contact point

Organisation

Avalo Therapeutics Inc.

Contact name

Mittie Doyle

Public contact point

Organisation

Avalo Therapeutics Inc.

Contact name

Mittie Doyle

Third parties 11

Locations

9 EU/EEA countries · 43 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 82 files

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

Application history

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