A Phase 2a, Randomized, Multicenter, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Multiple Subcutaneous Doses of TRIV-509 in Adults with Moderate to Severe Atopic Dermatitis

Trial ID: 2025-522113-35-00
Protocol: 509-101
Sponsor: Triveni Bio Inc.

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Diseases & Conditions

Dermatitis atopic

Objectives

The primary objective is to assess the efficacy of TRIV-509 administered by subcutaneous injection for 12 weeks in adults with moderate to severe atopic dermatitis. This evaluation is clinically relevant to determine the therapeutic benefit of this bispecific monoclonal antibody targeting kallikrein-5 and kallikrein-7 in managing moderate to severe disease manifestations.

The secondary objectives include:

• Further assessment of the efficacy of TRIV-509 administered by subcutaneous injection every 4 weeks for a total of 12 weeks in adults with moderate to severe atopic dermatitis.
• Evaluation of the safety and tolerability of TRIV-509 administered by subcutaneous injection every 4 weeks for a total of 12 weeks in adults with moderate to severe atopic dermatitis.
• Assessment of the pharmacokinetics of TRIV-509 administered by subcutaneous injection every 4 weeks for a total of 12 weeks in adults with moderate to severe atopic dermatitis.
• Evaluation of the immunogenicity of TRIV-509 administered by subcutaneous injection every 4 weeks for a total of 12 weeks in adults with moderate to severe atopic dermatitis.

Participants

This clinical trial enrolled a total of **36 participants** diagnosed with **atopic dermatitis**. The study population consisted of adults aged **18 to 75 years**, inclusive, with both male and female participants included. All participants had **chronic atopic dermatitis** classified as moderate to severe, active, and symptomatic. Eligible individuals were required to have a body weight of at least **40 kg** at screening. The trial population was selected based on participants who had required **systemic therapy** to achieve adequate control of their condition, could not use topical medications, or had a history of inadequate response to topical medications for at least 28 days. Participants were required to have had no significant flares in their atopic dermatitis for at least 28 days prior to screening. Regarding lifestyle considerations, all participants were required to apply a stable dose of **topical emollient** throughout the study and to minimize natural and artificial sunlight exposure, including refraining from using tanning booths, sun lamps, or other ultraviolet light sources during the trial. Additionally, participants were instructed to avoid excessive sun exposure and were not permitted to plan trips to sunny climates within 28 days before the study start. Those receiving concomitant medications for reasons other than atopic dermatitis were required to maintain stable dosing regimens.

Plans and Procedures

This is a Phase 2a, randomized, multicenter, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy, safety, and pharmacokinetics of multiple subcutaneous doses of TRIV-509 in adults with moderate to severe atopic dermatitis. The study investigates TRIV-509, a human IgG1 bispecific monoclonal antibody against kallikrein-5 and kallikrein-7, administered as a solution for injection via subcutaneous injection. The comparator is TRIV-509 placebo. The trial aims to assess the efficacy of TRIV-509 administered by subcutaneous injection for 12 weeks in adults with moderate to severe atopic dermatitis. The maximum treatment period is 14 weeks.

The primary endpoint is the percentage of participants with improvement of atopic dermatitis at Week 16. Secondary endpoints include the percentage of participants with improvement of atopic dermatitis at Week 16, percentage of participants with treatment-emergent adverse events (TEAEs), percentage of participants with serious adverse events (SAEs), changes in vital signs, ECG parameters, and safety laboratory values, single-dose and multiple-dose pharmacokinetic parameters, and percentage of participants with anti-TRIV-509 antibodies.

Eligible participants must be aged 18 to 75 years inclusive with chronic atopic dermatitis and no significant flares for at least 28 days prior to screening. Participants must have moderate to severe, active, and symptomatic atopic dermatitis and meet Pruritus NRS severity score requirements at baseline. Participants must have required systemic therapy to achieve adequate control of atopic dermatitis, cannot use topical medications, or have a history of inadequate response to topical medications for at least 28 days. Body weight must be at least 40 kg at screening. Female participants of childbearing potential must have negative pregnancy tests at screening and before the first dose, and must agree to use highly effective contraception with a failure rate of less than 1% per year until end of study or for at least 24 weeks after the last dose, whichever is later. Male participants of reproductive potential must refrain from donating sperm or fathering a child and must use highly effective contraception when having sexual intercourse with a partner of childbearing potential until end of study or for at least 24 weeks after the last dose, whichever is later. Participants must be willing to apply a stable dose of topical emollient throughout the study and minimize natural and artificial sunlight exposure during the study.

The estimated recruitment start date is December 30, 2025, and the estimated end date is June 29, 2027. The overall trial duration from recruitment start to estimated completion is approximately 18 months. Participant involvement includes screening, baseline visit on Day 1, treatment visits for 12 weeks with subcutaneous injections, and follow-up assessments through Week 16. Participants receiving concomitant medications for reasons other than atopic dermatitis must be on a stable dose defined as not starting a new drug, changing, or stopping dosage within 7 days or 5 half-lives, whichever is longer, before Day 1 and through the treatment duration. Early termination from the study may occur under conditions specified in the protocol, though specific termination criteria are not detailed in the provided information.

Treatment

The experimental treatment in this clinical trial is **TRIV-509**, a **human IgG1 bispecific monoclonal antibody** targeting **kallikrein-5** and **kallikrein-7**. The investigational medicinal product is manufactured by Triveni Bio, Inc. and is formulated as a **solution for injection**. The active substance is a protein of biological origin. TRIV-509 is administered via **subcutaneous injection** for a treatment period of 14 weeks in adults with moderate to severe **atopic dermatitis**. The study is designed to evaluate the efficacy, safety, and pharmacokinetics of multiple subcutaneous doses of TRIV-509 over a 12-week treatment period.

The comparator treatment used in this study is **TRIV-509 Placebo** (PRD12690501), which serves as the control intervention in this randomized, double-blind, placebo-controlled trial. The placebo is designed to match the experimental treatment to maintain blinding throughout the study. Both the experimental product and placebo are administered according to the same dosing schedule and route of administration to ensure consistency in study conduct and participant compliance monitoring.

Efficacy

Efficacy will be assessed through the evaluation of atopic dermatitis improvement in participants receiving treatment. The primary efficacy endpoint is the percentage of participants with improvement of AD at Week 16. Secondary efficacy endpoints include the percentage of participants with improvement of AD at Week 16, assessed through additional parameters. The treatment period extends for 14 weeks with subcutaneous administration of TRIV-509. Efficacy assessments will also incorporate Pruritus NRS severity score requirements measured at baseline to establish entry criteria for participants with moderate to severe, active, and symptomatic AD. The study design includes a 12-week treatment phase with efficacy evaluation continuing through Week 16 to capture treatment response in the study population.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Aged ≥ 18 to ≤75 years, inclusive, at the time of signing the informed consent. 2. Has chronic AD 3. Has had no significant flares in AD for at least 28 days prior to Screening, in the opinion of the Investigator. 4. Has moderate to severe, active, and symptomatic AD 5. Meets Pruritus NRS severity score requirements at baseline. 6. Has required systemic therapy to achieve adequate control of AD OR cannot use topical medications OR has a history of inadequate response to topical medications for at least 28 days, as judged by the Investigator. 7. Body weight ≥ 40 kg (88.2 pounds) at Screening
A participant is eligible to participate if not pregnant or breastfeeding, and one of the following conditions applies: a. Is of nonchildbearing potential (NCBP) as defined in Appendix 4: Contraceptive and Barrier Guidance. OR b. Is of childbearing potential (CBP) and has a negative serum pregnancy test at Screening and a negative urine pregnancy test before the first dose of study intervention on Day 1 AND must agree to use a contraceptive method that is highly effective (with a failure rate of < 1% per year), preferably with low user dependency, as described in Appendix 4: Contraceptive and Barrier Guidance until EOS or for at least 24 weeks after the last dose of study intervention, whichever is later. Note: If the form of contraception used is a hormonal contraceptive, the participant must be on a stable dose of the hormonal contraceptive from weeks before Day 1 until the EOS or for at least 24 weeks after the last study intervention administration, whichever is longer. AND agrees not to donate ova until the EOS or for at least 24 weeks after the last dose of study intervention, whichever is later.
Male participants of reproductive potential must a. refrain from donating sperm or fathering a child from Day 1 (first dose of study intervention) until at least 24 weeks after the last study intervention administration, AND b. must agree to use an additional highly effective contraceptive method with a failure rate of <1% per year, preferably with low user dependency, as described in Appendix 4: Contraceptive and Barrier Guidance, when having sexual intercourse with a partner of CBP until EOS or for at least 24 weeks after the last dose of study intervention, whichever is later. Note: If the female partner of a male participant uses any hormonal contraceptive, the female partner must be on a stable dose of hormonal contraceptive for ≥4 weeks before Day 1 until EOS or for at least 24 weeks after the last study intervention administration, whichever is longer.
Signed informed consent as described in Section 10.1.3, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. 11. Willing to apply a stable dose of topical emollient throughout the study. 12. If currently receiving concomitant medications for any reason other than AD, is on a stable dose defined as not starting a new drug, changing, or stopping dosage within 7 days or 5 half-lives (whichever is longer) before Day 1 and through the treatment duration of the study. 13. Has not had excessive sun exposure, is not planning a trip to a sunny climate, has not used tanning booths within 28 days before Day 1, and is willing to minimize natural and artificial sunlight exposure during the study and to not use tanning booths, sun lamps or other ultraviolet light sources during the study.

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Exclusion Criteria

Severe or uncontrolled medical conditions (including but not limited to cardiovascular, respiratory, endocrine, neurologic, immunologic, or psychiatric disease) that would put the participant at undue risk for participation in a clinical trial or compromise clinical trial interpretation. 2. History of cancer or lymphoproliferative disease within 5 years before Day 1. Participants with successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix remain eligible. 3. Had a major surgery within 8 weeks before Screening or has a major surgery planned during the study. 4. Evidence of an active and/or concurrent dermatologic condition (e.g., seborrheic dermatitis, psoriasis, acute allergic contact dermatitis) that would interfere with the Investigator or participant-driven evaluations of AD. 5. Active chronic or acute infection that requires treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 14 days before Day 1, or superficial skin infection (if requiring topical or systemic antibiotics) within 14 days before Day 1.
History of active tuberculosis (TB), positive QuantiFERON-Gold TB test, or two indeterminate QuantiFERON-Gold TB tests. If the participant has a history of latent TB and/or positive QuantiFERON-Gold TB test but no history of active TB or signs/symptoms consistent with active TB with a regiment and duration consistent with country-specific guidelines before Screening, the participant remains eligible. If the first QuantiFERON-Gold TB test is indeterminant but the second is negative, the participant remains eligible. 7. Positive human immunodeficiency virus (HIV) antibody test. 8. Positive hepatitis B surface antigen (HBsAg) OR hepatitis B core antibody (anti-Hbc) test; for positive hepatitis B core antibody only, if reflex hepatitis B surface antibody (anti-Hbs) is positive AND hepatitis B DNA PCR is negative, participant remains eligible. Refer to Section 10.5 for additional guidance on hepatitis B testing. 9. Positive hepatitis C antibody test result with reflex positive HCV RNA at Screening. Note: For participants previously treated for hepatitis C, treatment must have been completed at least 84 days prior to Screening, with negative HCV RNA documented at that time and no positive RNA results thereafter. 10. Alcohol use disorder or substance use disorder within the past 12 months.
Participant has a laboratory test result at Screening that would put the participant at undue risk for participation in a clinical trial or compromise clinical trial interpretation. 12. Known chronic liver disease, or elevations of AST or ALT ≥2× ULN, or total bilirubin 1.5× ULN at Screening. Participants with known Gilbert syndrome with persistent but otherwise not clinically significant elevations in total bilirubin remain eligible. 13. Use of topical treatments that could affect AD presentation or that could affect the assessment of AD (e.g., prescription moisturizers, moisturizers containing additives such as ceramide, hyaluronic acid, urea, or filaggrin; calcineurin inhibitors, tars, antibiotic creams, PDE-4 inhibitors, topical antihistamines, corticosteroids, bleach baths, and medical devices) within 14 days before Day 1. 14. Received phototherapy narrowband NB-UVB, broad-band phototherapy, psoralen-UV-A, or excimer laser within 28 days before Day 1. 15. Treatment with systemic immunosuppressive or immunomodulatory therapy that could affect AD (e.g., azathioprine, cyclosporine, systemic corticosteroids, Janus kinase inhibitors, methotrexate, mycophenolate-mofetil) within 28 days before Day 1.
Treatment with immunomodulatory biologics as follows: • Dupilumab or other biologic targeting IL-13 or IL-4Ra within 90 days before Day 1. • Cell-depleting biologics, including rituximab, within 180 days before Day 1. 17. Other marketed or investigational immunomodulatory biologics within 5 half-lives (if known) or 112 days before Day 1, whichever is longer. 18. Treatment with oral antihistamines for AD within 7 days before Day 1. Note: A daily oral antihistamine for non-AD symptoms (e.g., allergies) is permitted if the dose is stable for at least 14 days before Day 1 and plans to continue to use the same agent at the same dose through the EOS/EOT visit. 19. Currently receiving a nonbiological investigational product or device or has received one within 5 half-lives of the drug or 28 days (whichever is longer) before Day 1.
Only for Participants Consenting to Biopsy Collection 20. History of an allergic reaction or significant sensitivity to lidocaine or other local anesthetics. 21. History of hypertrophic scarring or keloid formation in scars or suture sites. 22. Has taken anticoagulant medication, such as heparin, low molecular weight (LMW)‑heparin, warfarin, antiplatelets, within 14 days before Day 1, or has a contraindication to skin biopsies. Note: Nonsteroidal anti-inflammatory drugs (NSAIDs) will not be considered antiplatelets and will be allowed.