HyBryte Cream for Cutaneous T-Cell Lymphoma

(FLASH2 Trial)

Recruiting at 17 trial locations

Overseen By Jennifer Bonfrisco

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Soligenix

Must not be taking: Topical steroids, Systemic steroids

Disqualifiers: Sun hypersensitivity, Allergy to HyBryte, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 39

Duration: 18 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cream treatment called HyBryte for cutaneous T-cell lymphoma (CTCL), specifically in its early stages, which appear as patches or plaques on the skin. The goal is to determine if applying HyBryte gel twice a week for 18 weeks can improve these skin symptoms. Individuals with CTCL who have at least three noticeable skin lesions and haven't recently used certain other treatments may qualify for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications before enrolling. You must stop using topical treatments for CTCL at least 2 weeks before, and systemic treatments like steroids or light therapy at least 4 weeks before joining the study.

Is there any evidence suggesting that HyBryte is likely to be safe for humans?

Research has shown that HyBryte, a cream for treating a type of skin cancer called lymphoma, is generally safe. One study found HyBryte safe for treating early-stage cutaneous T-cell lymphoma (CTCL), indicating most people can use it without serious side effects. The Data Monitoring Committee, responsible for patient safety, confirmed that HyBryte is well-tolerated. Thus far, it appears to be a safe choice for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cutaneous T-cell lymphoma?

HyBryte cream is unique because it uses hypericin, a photosensitive compound, which is not commonly found in current treatments for cutaneous T-cell lymphoma (CTCL). Unlike standard therapies such as radiation or systemic drugs like bexarotene and romidepsin, HyBryte is applied topically, providing a localized treatment option with potentially fewer systemic side effects. Researchers are excited about HyBryte because it represents a novel approach that could offer better tolerability and convenience for patients managing this chronic condition.

What evidence suggests that HyBryte might be an effective treatment for cutaneous T-cell lymphoma?

Research has shown that HyBryte, a cream containing hypericin, may help treat cutaneous T-cell lymphoma (CTCL) in the patch or plaque stage. In this trial, participants will receive either HyBryte or a placebo. Studies found that 75% of patients using HyBryte experienced positive results. This treatment works through a light-activated process. It is considered safe and generally well-tolerated by many patients. The consistent success observed in studies suggests it could be an effective treatment for CTCL. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with a specific skin cancer called cutaneous T-cell lymphoma (CTCL), stages IA, IB, or IIA. Participants must have at least three evaluable lesions and not be pregnant or nursing. They should agree to pregnancy testing before treatment and consent to follow the study rules.

Inclusion Criteria

Patients with a minimum of three (3) evaluable, discrete lesions

Patients willing to follow the clinical protocol and voluntarily give their written informed consent

I am not pregnant or nursing and agree to a pregnancy test before treatment.

Exclusion Criteria

History of allergy or hypersensitivity to any of the components of HyBryte

A Screening ECG with a QT interval >470 ms (corrected for heart rate using the Fridericia's formula)

I haven't used topical treatments on my skin cancer lesions for 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HyBryte or placebo gel applied twice weekly for 18 weeks, followed by visible light exposure

18 weeks

36 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• HyBryte

Trial Overview The trial tests HyBryte™, a topical medication applied directly on the skin, against a placebo in patients with patch/plaque phase CTCL (mycosis fungoides). The goal is to see if HyBryte™ can effectively treat this condition.

How Is the Trial Designed?

Group I: HyBryte (0.25% Hypericin) Experimental Treatment 1 Intervention

HyBryte gel is applied twice weekly for 18 weeks.

Group II: Placebo Placebo Group 1 Intervention

Placebo gel is indistinguishable from HyBryte gel, and is applied twice weekly for 18 weeks.

HyBryte is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as HyBryte for:

• Cutaneous T-cell lymphoma (CTCL)

Approved in European Union as HyBryte for:

• Cutaneous T-cell lymphoma (CTCL)

Approved in United Kingdom as HyBryte for:

• Cutaneous T-cell lymphoma (CTCL)

Who Is Running the Clinical Trial?

Soligenix

Lead Sponsor

Trials

12

Recruited

900+

Published Research Related to This Trial

Bexarotene gel is effective in resolving mycosis fungoides (MF) lesions and may work even better when combined with topical steroids or phototherapy, making it a promising treatment for early-stage patients.

DAB(389)IL-2 has shown a 30% remission rate in highly refractory CTCL patients, but due to potential side effects like capillary leak syndrome, it is reserved for advanced cases and requires careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bexarotene and DAB(389)IL-2 (denileukin diftitox, ONTAK) in treatment of cutaneous T-cell lymphomas: algorithms. Duvic, M.[2019]

Bexarotene gel is a new topical treatment for early-stage cutaneous T-cell lymphomas (CTCL) that has shown efficacy in patients with stage IA or IB disease, especially those who have not responded to or cannot tolerate traditional therapies.

This treatment is generally well tolerated and offers a more convenient administration compared to traditional skin-directed therapies, which often have significant side effects like skin damage and secondary malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bexarotene gel: a new skin-directed treatment option for cutaneous T-cell lymphomas. Martin, AG.[2018]

Vorinostat is an effective treatment for advanced cutaneous T-cell lymphoma (CTCL), showing a 30% overall response rate in Phase II studies, with significant reductions in skin lesions and a time to response of about 10 weeks.

The drug is generally well tolerated at the approved dose of 400 mg once daily, with common mild side effects like fatigue and nausea, and severe toxicities occurring in less than 6% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vorinostat: A novel therapy for the treatment of cutaneous T-cell lymphoma. Kavanaugh, SM., White, LA., Kolesar, JM.[2022]

Patients with cutaneous T-cell lymphoma who have aggressive features, such as cutaneous tumors or lymph node involvement, typically experience rapid disease progression and shorter survival rates.

Allogeneic hematopoietic stem cell transplant (HSCT) offers the only potentially curative treatment option, providing durable long-term remissions compared to high-dose chemotherapy, which often leads to recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose therapy and bone marrow transplantation in cutaneous T-cell lymphoma. Oyama, Y., Guitart, J., Kuzel, TM., et al.[2019]

Cutaneous T-cell lymphoma (CTCL) treatment is tailored to the specific stage and type of the disease, with early-stage therapies including phototherapy and local steroids, while higher stages may require systemic treatments like interferon alpha and bexarotene.

Due to high relapse rates in advanced CTCL, new treatment options are needed, and the fusion protein brentuximab-vedotin, which targets CD30, shows promising potential in clinical studies for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of mycosis fungoides and Sézary syndrome]. Nicolay, JP., Assaf, C.[2022]

In a clinical trial involving 67 adults with early-stage cutaneous T-cell lymphoma (CTCL), topical bexarotene gel demonstrated a 63% overall response rate, indicating its efficacy in treating this condition.

The gel was well tolerated by most patients, with mild to moderate side effects primarily limited to the application sites, and a median response duration of 99 weeks, suggesting it is a viable long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 and 2 trial of bexarotene gel for skin-directed treatment of patients with cutaneous T-cell lymphoma. Breneman, D., Duvic, M., Kuzel, T., et al.[2019]

In a phase 3 clinical trial involving 169 patients with early-stage mycosis fungoides-cutaneous T-cell lymphoma (MF/CTCL), topical synthetic hypericin ointment activated by visible light showed a significant improvement in lesion response rates compared to placebo, with a 16% response rate after 6 weeks, increasing to 49% after 3 treatment cycles.

The treatment demonstrated a favorable safety profile, with only mild local skin reactions reported and no serious adverse events, making it a promising nonmutagenic photodynamic therapy option for patients with early-stage MF/CTCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Topical Hypericin Photodynamic Therapy for Early-Stage Cutaneous T-Cell Lymphoma (Mycosis Fungoides): The FLASH Phase 3 Randomized Clinical Trial. Kim, EJ., Mangold, AR., DeSimone, JA., et al.[2023]

In a retrospective study of 21 patients treated with bexarotene for refractory cutaneous T-cell lymphoma (CTCL), the overall response rate was 81%, with early-stage patients showing a complete response rate of 100% compared to 77.8% in advanced-stage patients.

Despite the high response rate, the study revealed a concerning overall mortality rate of 52.8%, particularly in advanced-stage patients, indicating that bexarotene may not be effective for all stages of CTCL and suggesting a need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polish Lymphoma Research Group Experience With Bexarotene in the Treatment of Cutaneous T-Cell Lymphoma. Sokolowska-Wojdylo, M., Florek, A., Zaucha, JM., et al.[2018]

Phototherapy, especially with treatments like broadband UVB and narrowband UVB, is effective for early-stage cutaneous T-cell lymphoma (CTCL), but it carries risks such as sunburn and potential skin damage.

Combining phototherapy with systemic treatments like IFN-alpha and retinoids can improve treatment outcomes and reduce the required doses of phototherapy, while extracorporeal photopheresis is beneficial for more advanced cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of phototherapy in cutaneous T-cell lymphoma. Pothiawala, SZ., Baldwin, BT., Cherpelis, BS., et al.[2010]

Citations

1. ir.soligenix.com ir.soligenix.com/2025-04-14-Positive-Outcome-in-75-of-CTCL-Patients-Treated-with-HyBryte-TM-for-18-Weeks

Positive Outcome in 75% of CTCL Patients Treated with ... Interim Results from FDA-Funded Study Reinforces HyBryte's™ Rapid Response and Strong Safety Profile. PRINCETON, N.J., April 14, ...

2. onclive.com onclive.com/view/hybryte-has-an-acceptable-safety-profile-in-cutaneous-t-cell-lymphoma

HyBryte Has an Acceptable Safety Profile in Cutaneous T- ... HyBryte shows a promising safety profile in CTCL treatment, confirmed by the Data Monitoring Committee in the phase 3 FLASH2 study. The therapy ...

3. cancernetwork.com cancernetwork.com/view/synthetic-hypericin-achieves-treatment-success-in-cutaneous-t-cell-lymphoma

Synthetic Hypericin Achieves Treatment Success in ... Synthetic hypericin (HyBryte™), a first-in-class photodynamic therapy utilizing light for activation, achieved treatment success in 75% of a ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06470451

NCT06470451 | Confirmatory Study of Topical HyBryte™ ... The study will evaluate the efficacy and safety of HyBryte (0.25% hypericin) gel or placebo gel applied twice weekly for 18 weeks. Treated lesions will be ...

5. ir.soligenix.com ir.soligenix.com/2025-10-07-Soligenix-Achieves-Important-Safety-Milestone-in-its-Confirmatory-Phase-3-Clinical-Trial-of-HyBryte-TM-for-the-Treatment-of-Cutaneous-T-Cell-Lymphoma

News Releases Despite the statistically significant result achieved in the first HyBryte™ (SGX301) Phase 3 clinical trial for the treatment of cutaneous T- ...

6. ir.soligenix.com ir.soligenix.com/2025-10-14-Soligenix-Updates-United-States-Medical-Advisory-Board-for-Cutaneous-T-Cell-Lymphoma

Soligenix Updates United States Medical Advisory Board for ... HyBryte™ (research name SGX301) is a novel, first-in-class, photodynamic therapy utilizing safe, visible light for activation. The active ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02448381

Topical SGX301 (Synthetic Hypericin) for the Treatment of ... To evaluate the use of SGX301, a topical photosensitizing agent, to treat patients with patch/plaque phase cutaneous T-cell lymphoma (mycosis fungoides).