HyBryte (Synthetic Hypericin) Versus Valchlor (Mechlorethamine) in the Treatment of CTCL

Participants will be randomized to receive HyBryte or Valchlor in a 1:1 randomization. Participants will be treated for 12 weeks and follow-up visits will be conducted 1, 2, and 4 weeks after completion of the treatment phase of the trial.

Prior to randomization, each participant will have at least 3 and up to 5 lesions identified (index lesions) that will be evaluated during the treatment phase and during the follow-up visits.

• Hypericin (Drug), also known as HyBryte, SGX301: HyBryte is synthetic hypericin formulated as a 0.25% hypericin ointment.
• Mechlorethamine Topical Gel (Drug), also known as Valchlor: Valchlor is an FDA-approved drug for the treatment of CTCL.

Primary outcomes

• Number of Participants With a Treatment Response in the Modified Composite Assessment of Index Lesion Disease Severity (mCAILS) Score [12 weeks]: A treatment response is defined as a ≥50% improvement in mCAILS score at Week 12 when compared to the mCAILS score at baseline. The Modified Composite Assessment of Index Lesion Disease Severity (mCAILS) score measures: Erythema (or redness) on a scale of 0 (no redness) to 8 (very red), Scaling on a scale of 0 (no scaling) to 8 (all of the lesion is covered by a very rough surface), Plaque Elevation on a scale of 0 (no evidence of plaque above normal skin level) to 3 (plaque shows marked elevation above normal skin level) and Surface Area on a scale of 0 (no lesion/surface area is 0 cm\^2) to 18 (the lesion is larger than 300 cm\^2). A lower score means a better outcome.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Minimum of 3 active treatment-accessible CTCL lesions
* Subjects must have a clinical diagnosis of cutaneous T-cell lymphoma (CTCL, mycosis fungoides), Stage IA, IB, or Stage IIA
* Subjects willing to follow the clinical protocol and voluntarily give their written informed consent
* Female subjects not pregnant nor nursing and willing to undergo a pregnancy test within 30 days prior to treatment initiation

Exclusion Criteria:

* History of severe allergic reaction to any of the components of HyBryte or mechlorethamine (Valchlor)
* Pregnancy or mothers who are breast-feeding
* All women of childbearing potential (WOCBP) and males with female partners who are WOCBP not willing to use effective contraception
* Subjects with history of sun hypersensitivity or photosensitive dermatoses (eg, porphyria, systemic lupus erythematosus (SLE), Sjogren's syndrome, etc.)
* Subjects whose condition is spontaneously improving
* Subjects receiving Valchlor (or any topical compound containing Mechlorethamine) in the preceding 2 months
* Subjects receiving topical steroids or other topical treatments (eg, targretin gel) on treatment accessible lesions for CTCL within 2 weeks of enrollment
* Subjects receiving systemic steroids, psoralen ultraviolet A (UVA) radiation therapy (PUVA), narrow band ultraviolet B (UVB) light therapy (NB-UVB) or carmustine (BCNU) or other systemic therapies for CTCL within 3 weeks of enrollment
* Subjects who have received electron beam irradiation within 3 months of enrollment
* Subjects with a history of significant systemic immunosuppression
* Subjects taking other investigational drugs or drugs of abuse within 30 days of enrollment
* Subject has any condition that, in the judgment of the Investigator, is likely to interfere with participation in the study
* Subjects receiving drugs known to cause photosensitization within 2 weeks of starting HyBryte therapy unless they have not had evidence of photosensitization after receiving a stable dose of the medication for a minimum of 4 weeks

Participant flow

Outcome results

• Number of Participants With a Treatment Response in the Modified Composite Assessment of Index Lesion Disease Severity (mCAILS) Score (Primary), Count of participants, Participants: HyBryte (0.25 % Hypericin) 3; Valchlor (Mechlorethamine) 1

Adverse events

Time frame: From enrollment until end of follow-up, up to 16 weeks

Other adverse events by term

• Results publication: Poligone B, Pullion C, Rumage A, Straube R, Donini O, Schaber CJ, Gilmore ES. Results from a Pilot Study of HyBryte (Topical Synthetic Hypericin) Versus Valchlor(R) (Mechlorethamine) in the Treatment of CTCL. Oncol Ther. 2026 Jun;14(2):693-705. doi: 10.1007/s40487-026-00430-1. Epub 2026 Apr 1. PMID 41920467

• Study Protocol and Statistical Analysis Plan (PDF, 2024-03-05)