Hypericin Ointment + Visible Light for Mycosis Fungoides

(RW-HPN-MF-01 Trial)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Ellen Kim, MD

Must not be taking: Topical steroids, Systemic steroids

Disqualifiers: Sun hypersensitivity, Systemic immunosuppression, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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 mycosis fungoides for up to 12 months (54 weeks). Funding Source: FDA OOPD.

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.

What data supports the effectiveness of the treatment Hypericin Ointment + Visible Light for Mycosis Fungoides?

Research shows that hypericin, when used with light therapy, has been effective in killing certain fungi and cancer cells in laboratory settings. It has also shown potential in treating skin conditions like psoriasis and cutaneous T-cell lymphoma, which are similar to mycosis fungoides. ^{1 2 3 4 5}

Is Hypericin Ointment + Visible Light safe for humans?

The treatment using topical synthetic hypericin ointment activated with visible light is described as having minimal short- and long-term adverse effects, indicating it is generally safe for humans. ^{6 7 8 9 10}

How is the treatment Hypericin Ointment + Visible Light unique for mycosis fungoides?

This treatment is unique because it uses hypericin, a natural compound activated by visible light, to specifically target and induce cell death in malignant T cells, which is different from traditional therapies that may not use light activation. This photodynamic approach allows for targeted treatment of skin disorders like mycosis fungoides, potentially reducing side effects compared to systemic treatments. ^{1 4 11 12 13}

Eligibility Criteria

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.

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

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

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

Trial Timeline

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

Treatment Details

Interventions

• Hypericin (Other)
• Visible Light (Other)

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.

Participant Groups

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.

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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 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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

In vitro fungicidal photodynamic effect of hypericin on Trichophyton spp. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Hypericin: a new laser phototargeting agent for human cancer cells. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Topical treatment of disseminated superficial actinic porokeratosis with hypericin-photodynamic therapy: a case report. [2021]

4. United States 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. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Hypericin in phototherapy. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Bexarotene and narrowband ultraviolet B phototherapy combination treatment for mycosis fungoides. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Monochromatic excimer light (308 nm) in patch-stage IA mycosis fungoides. [2006]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Contact Sensitization and Phototoxic and Photoallergic Potential of Tirbanibulin 1% Ointment in Healthy Volunteers. [2023]

9. United States 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. [2023]

10. United States 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. [2018]

11. United States 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. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

In vitro fungicidal photodynamic effect of hypericin on Candida species. [2022]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Skin photosensitization with topical hypericin in hairless mice. [2022]