Cryotherapy + Red Light PDT for Actinic Keratosis

Overseen By Ashley Reed

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Psoriasis Treatment Center of Central New Jersey

Must not be taking: 5-FU, Imiquimod, Retinoids, others

Disqualifiers: Pregnancy, Uncontrolled major disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatment sequences for actinic keratosis, a skin condition with rough, scaly patches caused by sun damage. Researchers aim to determine if cryotherapy (freezing treatment) followed by light therapy with a 10% ALA gel (Ameluz 10% Topical Gel) is more effective than the reverse order. The trial includes two experimental groups to compare results. Adults with 6-12 actinic keratosis spots on their face who can avoid excessive sun exposure are suitable candidates for this study. As a Phase 4 trial, this research focuses on understanding how these FDA-approved treatments can benefit more patients.

Will I have to stop taking my current medications?

The trial requires that you stop using certain skin treatments and medications, such as 5-fluorouracil, imiquimod, and systemic retinoids, for a specific period before starting. If you are using any investigational drugs, you must stop them at least 4 weeks before enrolling.

What is the safety track record for these treatments?

Research has shown that Ameluz 10% Topical Gel, when combined with red light therapy, is generally safe and well-tolerated. This treatment effectively clears actinic keratosis (AK) lesions, which are rough, scaly patches on the skin caused by sun damage.

One study found that the gel with red light therapy was as effective as another light treatment for clearing these lesions but resulted in fewer skin reactions. Another study indicated that using three tubes of the gel with red light was generally well-tolerated by patients.

Additionally, researchers have studied the combination of cryotherapy (a treatment that freezes skin lesions) with the gel and red light therapy for both effectiveness and safety. Overall, these findings suggest that the treatment is safe for most people, with only minor and manageable side effects reported. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using Ameluz 10% Topical Gel with cryotherapy and red light photodynamic therapy (PDT) for actinic keratosis because it offers a potentially more effective and quicker treatment. Traditional treatments for actinic keratosis, like cryotherapy alone or standard PDT, often require multiple sessions and can be uncomfortable. This new approach combines the benefits of cryotherapy with the enhanced targeting capability of PDT using the active ingredient 5-aminolevulinic acid (ALA) in Ameluz gel. By alternating the sequence of cryotherapy and PDT, researchers aim to maximize the destruction of precancerous cells, potentially reducing treatment time and improving patient outcomes.

What evidence suggests that this trial's treatments could be effective for actinic keratosis?

Research shows that Ameluz 10% Topical Gel, when combined with red light therapy, effectively treats actinic keratosis (AK) spots. One study found this combination works well on mild-to-moderate AK spots on the face and scalp, with patients experiencing good results and minimal discomfort.

Cryotherapy, which involves freezing the spots, has also proven very successful in treating AKs, with some studies reporting cure rates as high as 98.8%. In this trial, one arm will test cryotherapy followed by Ameluz and red light therapy, while another will test Ameluz and red light therapy followed by cryotherapy. Using cryotherapy before or after Ameluz and red light therapy can enhance treatment effectiveness, significantly reducing AK spots.

Overall, research strongly supports both treatment methods as effective options for managing actinic keratosis. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with Actinic Keratosis, a skin condition caused by sun damage, affecting the full face. Participants must be suitable for both cryotherapy and red light PDT treatments.

Inclusion Criteria

Able and willing to give written informed consent prior to performance of any study-related procedures

I am not pregnant and will use approved birth control if I can have children.

I have 6-12 mild to severe actinic keratosis spots on my face.

Exclusion Criteria

I haven't had skin treatments like peels or laser in the last 60 days.

I haven't taken retinoids in the last 6 months.

I haven't taken any experimental drugs recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cryotherapy followed by 10% ALA gel Red light PDT or 10% ALA gel Red Light PDT followed by cryotherapy

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ameluz 10% Topical Gel
• Cryotherapy
• Red Light PDT

Trial Overview The study is testing two sequences of treatment: one group receives cryotherapy followed by ALA gel and red light PDT; the other gets ALA gel with red light PDT first, then cryotherapy. There are 40 patients split evenly between the two groups.

How Is the Trial Designed?

Group I: cryotherapy followed by 10% ALA gel Red light PDT Experimental Treatment 3 Interventions

Group II: 10% ALA gel Red Light PDT followed by cryotherapy Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

Psoriasis Treatment Center of Central New Jersey

Lead Sponsor

Trials

18

Recruited

530+

Biofrontera Bioscience GmbH

Industry Sponsor

Trials

12

Recruited

1,900+

Published Research Related to This Trial

Photodynamic therapy (PDT) is 14% more effective than cryotherapy for achieving complete clearance of actinic keratoses (AKs) on the face and scalp, based on a meta-analysis of 641 participants.

The study analyzed 13 randomized trials and found that PDT not only improves lesion response but also offers favorable cosmetic results and patient satisfaction compared to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of photodynamic therapy vs other interventions in randomized clinical trials for the treatment of actinic keratoses: a systematic review and meta-analysis. Patel, G., Armstrong, AW., Eisen, DB.[2018]

The combination of a fractional ablative 2,940nm erbium:yttrium-aluminum-garnet laser with blue light photodynamic therapy (PDT) is a safe and effective treatment for actinic keratoses (AKs), as demonstrated in a clinical experience with six patients.

This laser-assisted drug delivery method offers a promising option for the field treatment of AKs, which are precursors to skin cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractional Ablative Laser-Assisted Photodynamic Therapy as Field Treatment for Actinic Keratoses: Our Anecdotal Experience. Wang, JV., Griffin, TD.[2021]

Tirbanibulin 1% ointment is an effective new treatment for actinic keratosis (AK), showing similar efficacy to established treatments like fluorouracil and photodynamic therapy, with an odds ratio of 11.1 for complete clearance.

The systematic review included 46 studies and confirmed that tirbanibulin has a favorable safety profile and can be applied in a single short treatment period, making it a convenient option for patients compared to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Efficacy and Safety of Tirbanibulin for Actinic Keratosis of the Face and Scalp in Europe: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. Heppt, MV., Dykukha, I., Graziadio, S., et al.[2022]

5-aminolaevulinic acid (Ameluz) has been authorized for use in the European Union to treat mild to moderate actinic keratosis on the face and scalp, based on its effectiveness in improving the complete response rate of lesions.

The treatment involves applying the gel to the lesions and surrounding area, followed by illumination with red light, which activates a compound that destroys the target cells; common side effects include local reactions at the application site.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency approval of 5-aminolaevulinic acid (Ameluz) for the treatment of actinic keratosis of mild to moderate intensity on the face and scalp: summary of the scientific assessment of the Committee for Medicinal Products for Human Use. Tzogani, K., Straube, M., Hoppe, U., et al.[2018]

Photodynamic therapy (PDT) using a methyl-ester of 5-aminolevulinic acid is effective in treating resistant actinic keratoses (AKs) while also providing excellent cosmetic results, such as improved skin smoothness.

In a case study of an elderly patient, PDT not only removed the AK lesion but also significantly reduced signs of photoaging, including wrinkles, as demonstrated by 3D-profilometry measurements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Hotline: Facial skin rejuvenation in a patient treated with photodynamic therapy for actinic keratosis. Bruscino, N., Rossi, R., Dindelli, M., et al.[2013]

Photodynamic therapy (PDT) is an effective first-choice treatment for actinic keratoses (AKs), but it can cause significant side effects like pain and inflammation during and after treatment.

This review suggests modifications to the classic PDT procedure, such as omitting curettage and reducing incubation time, which aim to decrease side effects while maintaining treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Counteracting Side-effects of Photodynamic Therapy for Actinic Keratoses. Wulf, HC., Heerfordt, IM.[2023]

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]

Aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) photodynamic therapy (PDT) are highly effective treatments for actinic keratosis (AK) and have shown high clearance rates for these lesions.

MAL/PDT offers advantages over ALA/PDT, including shorter incubation times, greater selectivity, reduced pain, fewer systemic side effects, and better cosmetic outcomes compared to traditional treatments like cryosurgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current methods for photodynamic therapy in the US: comparison of MAL/PDT and ALA/PDT. Lee, PK., Kloser, A.[2016]

In a study of 204 patients with actinic keratosis, photodynamic therapy (PDT) using methyl aminolevulinate showed a 91% lesion response rate, significantly outperforming cryotherapy (68%) and placebo PDT (30%).

PDT not only provided better clinical outcomes but also resulted in superior cosmetic results and higher patient satisfaction compared to cryotherapy, making it a preferred treatment option for patients with widespread lesions or those in cosmetically sensitive areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of photodynamic therapy using topical methyl aminolevulinate (Metvix) with single cycle cryotherapy in patients with actinic keratosis: a prospective, randomized study. Freeman, M., Vinciullo, C., Francis, D., et al.[2019]

Citations

1. ameluz.com ameluz.com/hcp/why-ameluz

Demonstrated efficacy – AMELUZ® and BF-RhodoLED® See the results of AMELUZ® and the BF-RhodoLED® lamp on patients with mild-to-moderate AK lesions on the face and scalp from a phase 3 clinical trial.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6440706/

Safety and Efficacy of Aminolevulinic Acid 10% Topical Gel ... GEL was equivalent to SOL for clearing AK lesions on the face and scalp with blue-light PDT; however, SOL caused significantly more local skin reactions.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1572100025002303

Painless PDT using 10% aminolevulinate gel and red light ... Short-contact red light PDT regimens are essentially painless and appear to provide very good AK lesion clearance.

4. us.ameluz.com us.ameluz.com/hcp/treat-the-field-with-pdt

treat the field with photodynamic therapy (pdt) These data were derived from an observational, non-interventional, prospective study including 305 patients. Patients were required to fill in a ...

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

208081Orig1s000 ... (ALA) in patients with actinic keratosis following topical application of a gel formulation containing 78 mg/g ALA. (Ameluz®) under maximal ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06745999

Cryotherapy in Combination with Red Light PDT for Actinic ... A Single Center, Observational Study to Evaluate the Effectiveness and Safety of Cryotherapy in Combination with 10% ALA Gel Red Light PDT in the Treatment of ...

7. jcadonline.com jcadonline.com/10-aminolevulinic-acid-gel-actinic-keratosis/

A Non-randomized, Open-label, Multicenter Study to ... It can be concluded that PDT with three tubes of 10% ALA gel and red light illumination on an expanded treatment field of 60cm 2 was generally well tolerated.