BF-200 ALA + PDT for Actinic Keratosis

Not currently recruiting at 13 trial locations

Overseen By Corinna Zogel, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Biofrontera Bioscience GmbH

Must not be taking: Immunosuppressants, Cytostatics, Glucocorticosteroids, others

Disqualifiers: Hypersensitivity to ALA, Porphyria, 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

Compensation: Varies

Number of Visits: 3

Duration: 16-28 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for actinic keratosis, a skin condition that causes rough, scaly patches on sun-exposed areas. Researchers are testing the effectiveness and safety of a gel called BF-200 ALA (Ameluz®) combined with a specific light therapy known as Photodynamic Therapy with Red Light LED Lamp. Participants will receive either the active treatment or a placebo, both followed by red light exposure. Individuals with 4 to 15 mild to moderate actinic keratosis spots on their arms, legs, neck, or trunk may be suitable 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 does not specify if you need to stop all current medications, but certain medications must be stopped before joining. You cannot use specific topical treatments within 3 months or certain systemic treatments within 6 to 12 weeks before screening. Check with the trial team for details on your specific medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that BF-200 ALA with photodynamic therapy (PDT) is well-tolerated. Research indicates that this treatment is effective for mild-to-moderate actinic keratosis (AK), which are rough, scaly patches on the skin caused by sun exposure. Reports from these studies suggest that most patients handle the treatment well, with side effects usually mild and temporary. Common reactions include some redness and swelling at the treatment area, which are normal and expected. Overall, current data suggests the treatment is safe for human use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for actinic keratosis?

Unlike the standard creams and gels for actinic keratosis that mainly rely on chemical action, BF-200 ALA is unique because it combines a topical application with photodynamic therapy (PDT) using red light. This treatment uses 5-aminolevulinic acid (5-ALA), which is activated by the red light to specifically target and destroy abnormal skin cells. Researchers are excited about this approach because it offers a double-action method, potentially providing a more precise treatment with fewer side effects compared to traditional options. Plus, the use of light activation allows for targeted treatment, which could lead to quicker and more effective results.

What evidence suggests that BF-200 ALA + PDT could be an effective treatment for actinic keratosis?

Research has shown that using BF-200 ALA with photodynamic therapy (PDT) effectively treats actinic keratosis (AK), which are rough, scaly patches on the skin caused by sun damage. One study found that this treatment cleared 86% of AK spots, demonstrating its strong effectiveness. Another study showed that this combination is not only effective but also well-tolerated, with most people experiencing no serious side effects. Participants in this trial may receive BF-200 ALA with PDT, indicating it could be a reliable treatment option for managing AK. ^{1 3 4 6 7}

Who Is on the Research Team?

Nathalie Zeitouni, MD

Principal Investigator

Medical Dermatology Specialists; Phoenix, Arizona, United States

Are You a Good Fit for This Trial?

This trial is for adults with 4-15 mild to moderate Actinic Keratosis lesions on extremities or neck/trunk. Participants must be in good health, not use tanning beds, and agree to a biopsy if needed. Women of childbearing age must have a negative pregnancy test and use contraception.

Inclusion Criteria

I have 4-15 mild to moderate skin lesions on my arms, legs, neck, or trunk.

Women who can have babies need to have a negative pregnancy test.

I am willing to stop using skin products in the treatment area 24 hours before my next visit.

Exclusion Criteria

Receipt of any investigational drug or medical product within 8 weeks before screening or simultaneous participation in another clinical study

I do not have any health issues that would make it hard to follow the study or affect my safety.

I do not have sunburn or skin conditions near the treatment area.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

1 visit (in-person)

Treatment

Participants receive photodynamic therapy (PDT) with BF-200 ALA or vehicle treatment

16-28 weeks

Multiple visits (in-person) depending on treatment schedule

Follow-up

Participants are monitored for safety and effectiveness after treatment

40 weeks

2 visits (in-person) at 6 and 12 months after last PDT

What Are the Treatments Tested in This Trial?

Interventions

• BF-200 ALA (Ameluz®)
• Photodynamic Therapy with Red Light LED Lamp

Trial Overview The study tests the safety and effectiveness of BF-200 ALA gel with RhodoLED lamp light therapy versus a placebo treatment for Actinic Keratosis. Patients will receive up to two treatments within about 12 weeks.

How Is the Trial Designed?

Group I: BF-200 ALA Experimental Treatment 1 Intervention

Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). Red light photodynamic therapy (PDT)

Group II: Vehicle Placebo Group 1 Intervention

Topical application of vehicle to BF-200 ALA containing no active ingredient. Red light photodynamic therapy (PDT)

BF-200 ALA (Ameluz®) is already approved in European Union, United Kingdom, United States for the following indications:

Approved in European Union as Ameluz for:

• Actinic keratosis of mild to moderate intensity on the face and scalp
• Actinic keratosis on extremities and trunk/neck

Approved in United Kingdom as Ameluz for:

• Actinic keratosis of mild to moderate intensity on the face and scalp
• Actinic keratosis on extremities and trunk/neck

Approved in United States as Ameluz for:

• Actinic keratosis of mild to moderate severity on the face and scalp

Who Is Running the Clinical Trial?

Biofrontera Bioscience GmbH

Lead Sponsor

Trials

12

Recruited

1,900+

Published Research Related to This Trial

In a study of 88 patients with actinic keratosis, photodynamic therapy using visible light combined with water-filtered infrared light (PD750) resulted in significantly lower pain scores compared to incoherent light (Wa1200L).

Both light sources showed similar efficacy rates for clearing lesions, with complete clearance rates remaining high at 85% to 91% after 1 month and 69% to 85% after 12 months, indicating that while pain levels differed, the effectiveness of treatment was largely comparable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled trial of photodynamic therapy of actinic keratosis comparing different red light sources. Giehl, KA., Kriz, M., Grahovac, M., et al.[2014]

In a study involving 27 patients with actinic keratosis, different doses of red light (70, 100, and 140 J/cm2) for ALA-PDT showed similar efficacy, with complete remission rates of 89% to 92% one month after treatment, indicating that lower doses can be effective.

The study suggests that a red light dose of 70 J/cm2 is sufficient for effective treatment, as it achieved comparable results to higher doses while also potentially reducing treatment-related pain, which was substantial across all doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of 3 different light doses in the treatment of actinic keratosis with 5-aminolevulinic acid photodynamic therapy: a randomized, observer-blinded, intrapatient, comparison study. Radakovic-Fijan, S., Blecha-Thalhammer, U., Kittler, H., et al.[2013]

Topical aminolevulinic acid (ALA) photodynamic therapy (PDT) was tested in a small study involving 26 patients with conditions like acne, photoaging, and vitiligo, showing promising results after three to four treatments.

The treatment was applied at very low strengths (1-2%) over large areas, and side effects were minimal and self-limited, indicating a good safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy with low-strength ALA, repeated applications and short contact periods (40-60 minutes) in acne, photoaging and vitiligo. Serrano, G., Lorente, M., Reyes, M., et al.[2021]

Photodynamic therapy (PDT) using BF-200 ALA demonstrated high long-term efficacy in treating actinic keratosis (AK), with 47% of patients remaining completely clear of lesions for at least 12 months after treatment, compared to 36% for the methyl aminolaevulinate (MAL) cream.

The recurrence rates for BF-200 ALA were lower than those for MAL, particularly in patients treated with narrow wavelength LED lamps, indicating that BF-200 ALA may offer a superior treatment outcome without any reported safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term (6 and 12 months) follow-up of two prospective, randomized, controlled phase III trials of photodynamic therapy with BF-200 ALA and methyl aminolaevulinate for the treatment of actinic keratosis. Dirschka, T., Radny, P., Dominicus, R., et al.[2021]

BF-200 ALA, a new gel formulation of 5-aminolaevulinic acid, demonstrated a significantly higher complete clearance rate for actinic keratosis (AK) lesions compared to placebo (78.2% vs. 17.1%) and was also more effective than the registered methyl-5-aminolaevulinate (MAL) cream (78.2% vs. 64.2%) in a study involving 600 patients.

The study highlighted that BF-200 ALA is a well-tolerated treatment option for AK, with varying efficacy and adverse events depending on the type of light source used during photodynamic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a multicentre, randomized, observer-blind phase III study in comparison with a registered methyl-5-aminolaevulinate cream and placebo. Dirschka, T., Radny, P., Dominicus, R., et al.[2016]

Photodynamic therapy (PDT) using aminolevulinic acid (ALA) is highly effective for clearing actinic keratoses (AKs) on the upper extremities, achieving an 88.7% clearance rate with occlusion after 12 weeks.

Using an occlusive dressing during the ALA treatment significantly enhances efficacy compared to non-occluded treatments, although it also increases the incidence and severity of some side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, randomized, vehicle-controlled phase 2 study of blue light photodynamic therapy with aminolevulinic acid HCl 20% topical solution for the treatment of actinic keratoses on the upper extremities: the effect of occlusion during the drug incubation period. Schmieder, GJ., Huang, EY., Jarratt, M.[2013]

Photodynamic therapy (PDT) using 5-aminolaevulinic acid (ALA) with a newly developed LED system is as effective as traditional incoherent lamps for treating actinic keratosis, showing similar complete remission rates of 84.3% for LEDs and 82.8% for incoherent lamps after 6 weeks.

Both treatment methods resulted in comparable levels of patient satisfaction, pain during treatment, and cosmetic outcomes, indicating that the LED system is a safe and effective alternative for ALA-PDT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo comparison of two different light sources for topical photodynamic therapy. Babilas, P., Kohl, E., Maisch, T., et al.[2013]

In a study of 243 patients, photodynamic therapy (PDT) using 20% aminolevulinic acid (ALA) and blue light resulted in a high efficacy rate, with 77% of patients achieving significant lesion clearing by week 8 and 89% by week 12, compared to only 18% and 13% in the placebo group.

The treatment was generally safe, with most side effects like erythema and edema resolving within 1 to 4 weeks, indicating that ALA PDT is a viable option for treating multiple actinic keratoses on the face and scalp.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy with aminolevulinic acid topical solution and visible blue light in the treatment of multiple actinic keratoses of the face and scalp: investigator-blinded, phase 3, multicenter trials. Piacquadio, DJ., Chen, DM., Farber, HF., et al.[2013]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26921093/

A randomized, double-blind, phase III, multicentre study to ... Field-directed therapy with BF-200 ALA and BF-RhodoLED lamp is highly effective and well tolerated for multiple mild-to-moderate AK lesions, providing greatly ...

2. ameluz.com ameluz.com/hcp/why-ameluz

Demonstrated efficacy – AMELUZ® and BF-RhodoLED® A randomized, double-blind, phase III, multicentre study to evaluate the safety and efficacy of BF-200 ALA (Ameluz) vs. placebo in the field-directed treatment ...

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2016/208081Orig1s000ClinPharmR.pdf

208081Orig1s000 Title: A single center, non-randomized, open-label, placebo-controlled, fixed sequence. Phase I study to evaluate the PK of 5-aminolevulinic ...

4. jaad.org jaad.org/article/S0190-9622(21)00575-2/fulltext

Red light photodynamic therapy with BF-200 ALA showed ... Treatment with BF-200 ALA and red light photodynamic therapy was well tolerated and yielded positive responses, with 86% of lesions cleared.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04319159

Study to Evaluate the Safety of BF-200 ALA (Ameluz®) for ... The aim of this study is to assess the pharmacokinetics (PK) of the parent drug 5-aminolevulinic acid (ALA) and its active metabolite protoporphyrin IX ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04319159?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(Aminolevulinic%20acid))&rank=6

Study to Evaluate the Safety of BF-200 ALA (Ameluz®) for ... The aim of this study is to assess the pharmacokinetics (PK) of the parent drug 5- aminolevulinic acid (ALA) and its active metabolite protoporphyrin IX ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12007652/

A Non-randomized, Open-label, Multicenter Study to Evaluate ... Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a multicentre, randomized, observer-blind phase III study in ...