Hypericin Ointment + Visible Light for Mycosis Fungoides

(RW-HPN-MF-01 Trial)

Overseen By Laura Cesar

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ellen Kim, MD

Must not be taking: Topical steroids, Systemic steroids

Disqualifiers: Sun hypersensitivity, Systemic immunosuppression, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 2

Duration: 54 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a synthetic hypericin ointment (HyBryte) combined with visible light for treating mycosis fungoides, a type of skin lymphoma, over up to 12 months. Participants will apply the ointment to affected skin areas and expose those areas to visible light twice a week. The trial targets individuals diagnosed with mycosis fungoides who have skin patches or plaques of any size and abnormal but non-cancerous lymph nodes. As a Phase 2 trial, the research focuses on assessing the treatment's efficacy in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications before enrolling. You must stop topical treatments for CTCL at least 2 weeks before, and systemic treatments like steroids or light therapy at least 3 weeks before joining the trial.

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

Research has shown that HyBryte, a treatment using a special ointment and safe, visible light, is effective and generally safe for early-stage mycosis fungoides, a type of skin cancer. The ointment contains synthetic hypericin, activated by the light to treat the skin.

Participants in studies have found this treatment well-tolerated, with most not experiencing serious side effects. While minor side effects can occur, the treatment aims to minimize discomfort.

Overall, evidence suggests this treatment is a promising and safe option for those considering joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about HyBryte because it offers a unique approach to treating mycosis fungoides, a type of cutaneous T-cell lymphoma. Unlike standard treatments that often involve systemic therapies or topical corticosteroids, HyBryte combines a natural compound called hypericin with visible light. This combination allows for targeted treatment of skin lesions, potentially reducing systemic side effects. Hypericin is derived from St. John's Wort and is activated by light exposure, which could offer a more precise and less invasive option for patients.

What evidence suggests that Hypericin ointment with visible light might be an effective treatment for mycosis fungoides?

Research shows that HyBryte, a special ointment activated by light, has promising results for treating mycosis fungoides, a type of skin cancer. In earlier studies, 75% of patients with this skin cancer, known as cutaneous T-cell lymphoma (CTCL), experienced positive results after 18 weeks of using HyBryte. This trial will evaluate HyBryte (0.25% Hypericin) with Visible Light, using photodynamic therapy, where light helps the ointment target cancer cells. Experts agree that this approach works well for early stages of CTCL and is generally easy for patients to tolerate. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with a specific skin cancer called mycosis fungoides, stages 1A to 2A. Participants must be willing to follow the study rules and not be pregnant or breastfeeding. They should use birth control and cannot have allergies to the treatment components or conditions that worsen with light exposure.

Inclusion Criteria

I am not pregnant or nursing and agree to use birth control or abstain from sex during the study.

I have been diagnosed with early-stage cutaneous T-cell lymphoma.

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

Exclusion Criteria

I haven't taken any medication that increases sun sensitivity in the last 2 weeks, or I've been on a stable dose for over 4 weeks without issues.

I am not willing to use birth control.

Subject with any condition that, in the judgment of the PI, is likely to interfere with participation in the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HyBryte ointment treatment followed by visible light activation twice a week for up to 54 weeks

54 weeks

2 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Hypericin
• Visible Light

Trial Overview The trial tests synthetic hypericin ointment (HyBryte) combined with visible light on patients over a period of up to 12 months. The aim is to see if this continuous treatment benefits those suffering from mycosis fungoides.

How Is the Trial Designed?

Group I: HyBryte (0.25 % Hypericin) with Visible Light Experimental Treatment 2 Interventions

HyBryte (0.25 % hypericin) ointment will be applied to CTCL lesions and treated with visible light 24 (±6) hours later starting at 5 J/cm\^2. Drug application/light sessions will be done twice a week (at least 2 calendar days apart) for up to 54 weeks.

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

Approved in United States as HyBryte for:

• Mycosis fungoides
• Cutaneous T-cell lymphoma

Approved in European Union as HyBryte for:

• Mycosis fungoides
• Cutaneous T-cell lymphoma

Who Is Running the Clinical Trial?

Ellen Kim, MD

Lead Sponsor

Trials

1

Recruited

20+

Office of Orphan Products Development

Collaborator

Trials

1

Recruited

20+

Soligenix

Industry Sponsor

Trials

12

Recruited

900+

Published Research Related to This Trial

Hypericin, when activated by laser light, can reduce the viability of human cancer cells by over 95%, demonstrating its potential as a powerful agent in phototherapy for various cancer types.

This study found that hypericin combined with laser activation was highly effective across multiple cancer cell lines, while showing minimal toxicity when used alone, suggesting it could be a safe option for targeted cancer treatment using imaging-guided laser techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypericin: a new laser phototargeting agent for human cancer cells. VanderWerf, QM., Saxton, RE., Chang, A., et al.[2021]

Topical hypericin, a dye from St. John's wort, was tested in photodynamic therapy (PDT) for two patients with disseminated superficial actinic porokeratosis (DSAP).

While one patient showed a partial response to the treatment, overall, topical hypericin-PDT is not considered a promising option for treating DSAP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical treatment of disseminated superficial actinic porokeratosis with hypericin-photodynamic therapy: a case report. Boiy, A., de Witte, PA., Roelandts, R.[2021]

Hypericin can effectively penetrate the skin when formulated in an emulsifying ointment with solketal, showing potential as a topical treatment for psoriasis and other skin conditions.

While hypericin shows promise for localized treatment, high doses administered systemically can lead to severe photosensitivity and toxicity, highlighting the importance of careful dosing and formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skin photosensitization with topical hypericin in hairless mice. Kamuhabwa, AR., Roelandts, R., de Witte, PA.[2022]

Hypericin, a natural photosensitizer, demonstrated a strong in vitro fungicidal effect against dermatophytes, specifically Trichophyton rubrum and Trichophyton mentagrophytes, achieving a 3-log reduction in fungal viability with optimal concentrations and exposure times.

The study found that hypericin localized within the dermatophytes, indicating its potential as an effective treatment for localized fungal infections like tinea pedis and onychomycosis when used in photodynamic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro fungicidal photodynamic effect of hypericin on Trichophyton spp. Paz-Cristobal, MP., Gilaberte, Y., Alejandre, C., et al.[2021]

Adjunctive excimer laser therapy combined with psoralen plus ultraviolet A (PUVA) and oral bexarotene effectively treated recalcitrant mycosis fungoides (MF) lesions in a patient, leading to both clinical and histologic resolution.

The treatment regimen was well-tolerated, with only mild and short-lived side effects, suggesting it is a safe option for managing cutaneous MF lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case experience of 308-nm excimer laser therapy compatibility with PUVA and oral bexarotene for the treatment of cutaneous lesions in mycosis fungoides. Huang, J., Cowper, S., Moss, J., et al.[2018]

An 81-year-old male with mycosis fungoides showed significant improvement when treated with a combination of bexarotene and narrowband ultraviolet B (NB-UVB) therapy, suggesting this approach can enhance therapeutic efficacy.

The patient's condition worsened when NB-UVB was interrupted, highlighting the importance of this combination therapy in managing plaque-stage mycosis fungoides and indicating it may be a safe alternative for patients with contraindications to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bexarotene and narrowband ultraviolet B phototherapy combination treatment for mycosis fungoides. Lokitz, ML., Wong, HK.[2018]

In a study involving 4 patients with early-stage mycosis fungoides (MF), treatment with 308-nm monochromatic excimer light resulted in complete clinical and histological remission of all treated lesions, with a mean of 6.5 sessions per patient.

The treatment was well-tolerated, with no significant side effects reported, and all lesions remained in stable remission for up to 28 months, suggesting that this phototherapy could be an effective option for patch stage IA MF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monochromatic excimer light (308 nm) in patch-stage IA mycosis fungoides. Mori, M., Campolmi, P., Mavilia, L., et al.[2006]

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]

Hypericin, when activated by light, effectively inhibits the growth of malignant T cells from patients with cutaneous T cell lymphoma, with IC50 values indicating significant potency (0.34 to 0.53 microM).

The compound induces high levels of apoptosis (up to 94%) in malignant T cells, demonstrating its potential as a targeted treatment for this type of cancer, while also affecting normal cells to a lesser extent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photoactivated hypericin is an anti-proliferative agent that induces a high rate of apoptotic death of normal, transformed, and malignant T lymphocytes: implications for the treatment of cutaneous lymphoproliferative and inflammatory disorders. Fox, FE., Niu, Z., Tobia, A., et al.[2021]

Hypericin was successfully used as a photosensitizer in photodynamic therapy for a patient with recurrent malignant mesothelioma, showing initial satisfactory results when applied locally after previous treatment with hematoporphyrin derivatives.

The combination of hypericin and hematoporphyrin derivatives demonstrated potential for enhanced tumor destruction, although subsequent treatments did not yield the same therapeutic effect, indicating the need for further investigation into optimal application methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypericin in phototherapy. Koren, H., Schenk, GM., Jindra, RH., et al.[2021]

Tirbanibulin 1% ointment, used for treating actinic keratosis, was found to be safe in three phase 1 studies involving a total of 319 healthy adults, showing no signs of sensitization, phototoxicity, or photoallergy.

The studies indicated that while mild-to-moderate contact irritations were reported, the overall safety profile supports its use as a topical treatment applied once daily for 5 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contact Sensitization and Phototoxic and Photoallergic Potential of Tirbanibulin 1% Ointment in Healthy Volunteers. Dosik, J., Cutler, DL., Fang, J., et al.[2023]

Topical hypericin, when combined with visible light therapy, showed significant improvement in skin lesions for patients with mycosis fungoides and plaque psoriasis after 6 weeks of treatment, indicating its efficacy as a therapeutic option.

The study suggests that hypericin therapy is well-tolerated and could serve as an effective alternative to standard treatments like psoralen plus ultraviolet A, although it was conducted with a small number of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II placebo-controlled study of photodynamic therapy with topical hypericin and visible light irradiation in the treatment of cutaneous T-cell lymphoma and psoriasis. Rook, AH., Wood, GS., Duvic, M., et al.[2021]

Hypericin shows a strong fungicidal effect against various Candida species, achieving a 3 log reduction at lower concentrations and light doses, indicating its potential as an effective treatment in photodynamic therapy (PDT).

The study found that hypericin concentrations below 1 μM and light doses under 37 J cm(-2) can preserve healthy skin cells, suggesting that hypericin PDT can effectively target fungal infections like C. albicans while minimizing damage to surrounding tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro fungicidal photodynamic effect of hypericin on Candida species. Rezusta, A., López-Chicón, P., Paz-Cristobal, MP., et al.[2022]

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 ... About HyBryte™. HyBryte™ (research name SGX301) is a novel, first-in-class, photodynamic therapy utilizing safe, visible light for activation.

2. clfoundation.org clfoundation.org/hybryte-flash

HyBryte™ (FLASH) May 2025 - Dr. Ellen Kim shares her update on the real world clinical study of the treatment of mycosis fungoides with hypericin ointment and visible light.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05872854

Treatment of Mycosis Fungoides With Hypericin Ointment ... The goal of this clinical trial is to assess the benefit of continuous treatment with synthetic hypericin ointment (HyBryte) and visible light in patients with ...

4. 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 ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35857290/

The FLASH Phase 3 Randomized Clinical Trial The findings of this randomized clinical trial indicate that synthetic hypericin PDT is effective in early-stage patch and plaque MF/CTCL and has a favorable ...

6. jamanetwork.com jamanetwork.com/journals/jamadermatology/fullarticle/2794396

Efficacy and Safety of Topical Hypericin Photodynamic ... Topical synthetic hypericin activated with visible light is an effective and well-tolerated PDT for early-stage MF/CTCL.

7. ir.soligenix.com ir.soligenix.com/2025-01-14-HyBryte-TM-Expanded-Treatment-Continues-to-Demonstrate-Positive-Outcomes-in-Early-Stage-Cutaneous-T-Cell-Lymphoma

HyBryte™ Expanded Treatment Continues to Demonstrate ... HyBryte™ (research name SGX301) is a novel, first-in-class, photodynamic therapy utilizing safe, visible light for activation. The active ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06149247

Study Details | NCT06149247 | HyBryte (Synthetic ... Minimum of 3 active treatment-accessible CTCL lesions; Subjects must have a clinical diagnosis of cutaneous T-cell lymphoma (CTCL, mycosis fungoides), Stage IA, ...