BF-200 ALA + PDT for Actinic Keratosis

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

172 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment BF-200 ALA + PDT for actinic keratosis?

Research shows that photodynamic therapy (PDT) with BF-200 ALA, a gel formulation of 5-aminolevulinic acid (ALA), has high clearance rates for mild-to-moderate actinic keratosis (AK) and is more effective than a similar treatment using methyl aminolaevulinate (MAL) cream. ^{1 2 3 4 5}

Is BF-200 ALA + PDT safe for humans?

Photodynamic therapy (PDT) with BF-200 ALA has been shown to be a safe treatment option for actinic keratosis, a skin condition, in several studies. It is generally well-tolerated in humans, with no major safety concerns reported. ^{1 2 4 6 7}

What makes BF-200 ALA + PDT unique for treating actinic keratosis?

BF-200 ALA + PDT is unique because it uses a nanoemulsion gel formulation of 5-aminolevulinic acid (ALA) that improves skin penetration and stability, leading to higher clearance rates of actinic keratosis compared to other treatments like methyl aminolaevulinate (MAL) cream. ^{1 2 3 4 8}

What is the purpose of this trial?

The aim of this study is to test the safety. tolerability and efficacy of field-directed photodynamic therapy (PDT) with 10% aminolevulinic acid gel (Ameluz®, BF-200 ALA) in combination with one of the narrow spectrum red light RhodoLED lamps in comparison to vehicle treatment for actinic keratosis (AK) on the extremities and neck/trunk.

Research Team

Nathalie Zeitouni, MD

Principal Investigator

Medical Dermatology Specialists; Phoenix, Arizona, United States

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2016]

2. England 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. [2021]

3. France pubmed.ncbi.nlm.nih.gov

A controlled trial of photodynamic therapy of actinic keratosis comparing different red light sources. [2014]

4. England pubmed.ncbi.nlm.nih.gov

In vitro and in vivo comparison of two different light sources for topical photodynamic therapy. [2013]

5. United States 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. [2021]

6. United States 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. [2013]

7. United States 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. [2013]

8. United States 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. [2013]