FLASH [Fluorescent Light Activated Synthetic Hypericin] Clinical Study: Topical SGX301 (Synthetic Hypericin) for the Treatment of Cutaneous T-Cell Lymphoma (Mycosis Fungoides)

Study Overview
=================
Brief Summary
-----------------
To evaluate the use of SGX301, a topical photosensitizing agent, to treat patients with patch/plaque phase cutaneous T-cell lymphoma (mycosis fungoides).

Official Title
-----------------
A Phase 3 Multicenter, Randomized, Double-Blind, Placebo Controlled Study to Determine the Efficacy of Topical SGX301 (Synthetic Hypericin) and Fluorescent Bulb-Light Irradiation for the Treatment of Cutaneous T-Cell Lymphoma

Conditions
-----------------
Cutaneous T-Cell Lymphoma

Intervention / Treatment
-----------------
* Drug: SGX301 (synthetic hypericin)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must have a clinical diagnosis of CTCL (mycosis fungoides), Stage IA, Stage IB, or Stage IIA. Subjects must have a minimum of three (3) evaluable, discrete lesions. Subjects must be willing to refrain from sunbathing for the duration of the study. Exclusion Criteria: History of sun hypersensitivity and photosensitive dermatoses including porphyria, systemic lupus erythematosus, Sjögren's syndrome, xeroderma pigmentosum, polymorphous light eruptions or radiation therapy within 30 days of enrolling. Pregnancy or mothers who are breast feeding. Males and females not willing to use effective contraception. Unhealed sunburn. Subjects receiving topical steroids or other topical treatments for CTCL within 2 weeks. Subjects receiving systemic steroids, nitrogen mustard, psoralen UVA radiation therapy (PUVA), narrow band UVB light therapy (NB-UVB) or carmustine (BCNU) or other systemic therapies for CTCL within 3 weeks of enrollment. Subjects with significant history of systemic immunosuppression due to drugs or infection with HIV or HTLV 1. Subjects taking other investigational drugs or drugs of abuse within 30 days of entry into this study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SGX301<br>Three treatment cycles, each six (6) weeks followed by a two (2) week rest period. Treatment uses 0.25% SGX301 in USP Hydrophilic Ointment (or placebo) applied twice per week followed by fluorescent light therapy. Cycle 1: Patients randomized 2:1 to active/placebo will have three (3) index lesions treated and evaluated. Cycle 2: All patients will have three (3) index lesions treated and evaluated with active SGX301 ointment. Cycle 3: All patients will be given the opportunity to enter an open-label cycle of active SGX301 ointment treatment for all lesions (index and non-index). | Drug: SGX301 (synthetic hypericin)<br>* 0.25% SGX301 in USP Hydrophilic Ointment applied twice per week, covered by opaque bandage for 12-24 hours, then treated with an initial dose of 5 J/cm^2 fluorescent light.<br>* Other names: Synthetic Hypericin;|
| Placebo Comparator: Placebo<br>Placebo ointment is indistinguishable from ointment containing active SGX301 and is only used in Cycle 1. Treatment paradigm (ointment application and fluorescent light therapy) is identical. | Drug: Placebo<br>* USP Hydrophilic Ointment applied twice per week, covered by opaque bandage for 12-24 hours, then treated with an initial dose of 5 J/cm^2 fluorescent light.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Responders and Non-Responders With a Treatment Response in 3 Treated Lesions as Defined as a ≥50% Improvement in the Composite Assessment of Index Lesion Disease Severity (CAILS) Score When Compared to Patients Receiving Placebo | The percentage of patients achieving a treatment response in each of the 2 treatment groups. A treatment response was defined as a ≥50% improvement in CAILS score at Week 8 when compared to the CAILS score at baseline. The Composite Assessment of Index Lesion Disease Severity (CAILS) 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. The overall CAILS score was calculated by adding the total score as described above for each of the 3 lesions. The overall CAILS score has a range of 0 to 111. A lower score means a better outcome. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Responders and Non-Responders With a Treatment Response in 3 Treated Lesions as Measured by the Composite Assessment of Index Lesion Disease Severity (CAILS) Score (Cycle 1 and 2 SGX301 vs Cycle 1 Placebo) | The percentage of patients achieving a treatment response at Week 16 that received SGX301 for both Cycle 1 and 2 compared to the response rate in patients that received Placebo in Cycle 1. The Composite Assessment of Index Lesion Disease Severity (CAILS) score was measured as previously described. | 16 weeks | 
| Number of Responders and Non-Responders With a Treatment Response of 3 Treated Lesions as Measured by the Composite Assessment of Index Lesion Disease Severity (CAILS) Score in Patients Who Received 3 Cycles of SGX301 | The percentage of patients achieving a treatment response at Week 24 compared at Week 16 in SGX301 treatment group. A treatment response was defined as a ≥50% improvement in CAILS score when compared to the CAILS score at baseline. The Composite Assessment of Index Lesion Disease Severity (CAILS) score was measured as previously described. | 24 weeks | 
| Patch Lesion Response Rates With Extended Treatment (Cycle 1 & 2 SGX301 vs Cycle 1 Placebo) | The proportion of patch lesions achieving a treatment response at Week 16 in the SGX301 treatment group compared to Week 8 in the Placebo treatment group. A treatment response was defined as a ≥50% improvement in CAILS score when compared to the CAILS score at baseline for individual lesions. The Composite Assessment of Index Lesion Disease Severity (CAILS) score was measured as previously described. | 16 weeks | 
| Plaque Lesion Response Rates With Extended Treatment (Cycle 1 & 2 SGX301 vs Cycle 1 Placebo) | The proportion of plaque lesions achieving a treatment response at Week 16 in the SGX301 treatment group compared to Week 8 in the Placebo treatment group. A treatment response was defined as a ≥50% improvement in CAILS score when compared to the CAILS score at baseline for individual lesions. The Composite Assessment of Index Lesion Disease Severity (CAILS) score was measured as previously described. | 16 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CTCL, Mycosis fungoides, Hypericin, SGX301, MF