Neoplasms

All Conditions

Rare Diseases

Bowen's Disease

Carcinoma

Carcinoma, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Anti-Arrhythmia Agents

Channel Blockers

Central Nervous System Depressants

All Drugs and Chemicals

Dermatologic Agents

Lidocaine

Anesthetics

Aminolevulinic Acid

Prilocaine

Lidocaine, Prilocaine Drug Combination

Methyl 5-aminolevulinate

Protoporphyrin IX

Anesthetics, Local

Sodium Channel Blockers

Diuretics, Potassium Sparing

Photosensitizing Agents

Patients were randomly assigned to receive either AFL-PDT or MAL-PDT in a 1:1 ratio. As result, the patients were randomized to treatment with AFL-PDT or MAL-PDT

The lesions were then cleansed with saline gauze, and a lidocaine-prilocaine 5% cream (EMLA®; Astra Pharmaceuticals, LP, Westborough, MA, USA) was applied to the treatment area for 30 min under occlusion

lidocaine-prilocaine 5% cream application

After the anesthetic cream was removed, AFL was performed using a 2940-nm Er:YAG AFL (Joule; Sciton, Inc., Palo Alto, CA, USA) with a 500 µm ablation depth, level 1 coagulation, 22% treatment density, and a single pulse

2940-nm Er:YAG AFL pretreatment

Immediately after the AFL, a 1-mm thick layer of methyl-aminolevulinate (16% Metvix® cream; PhotoCure ASA, Oslo, Norway) was applied to the lesion and to 5 mm of the surrounding healthy tissue. The area was covered with an occlusive dressing (Tegaderm; 3M, Co., Saint Paul, MN, USA) for 3 h, after which the remaining cream was removed with saline gauze, and the red fluorescence of porphyrins was visualized with Wood's light.

methyl-aminolevulinate application

Each treatment area was then separately illuminated using red light-emitting diode lamps (Aktilite CL128; Galderma S.A., Bruchsal, Germany) with peak emission at 632 nm and a total light dose of 37 J/cm2. Areas scheduled to receive MAL-PDT received the second treatment 7 days later. During the illumination, patients were asked to evaluate pain intensity using an 11-point visual analog scale.

Illuminating using red light-emitting diode lamps

Er:YAG ablative fractional laser-assisted methyl aminolevulinate photodynamic therapy (AFL-PDT) has shown significantly higher efficacy and a lower recurrence rate at 12 months than methyl aminolevulinate photodynamic therapy (MAL-PDT) for treatment of Bowen's disease (BD). However, long-term follow up data are not available.

To compare the long-term efficacy and recurrence rates of AFL-PDT and standard MAL-PDT for the treatment of lower extremity BD.

Long-term Efficacy of Ablative Fractional Laser-assisted Photodynamic Therapy for Treatment of Lower Extremity Bowen's Disease

Long-term Efficacy of Ablative Fractional Laser-assisted Photodynamic Therapy for Treatment of Lower Extremity Bowen's Disease: A Prospective, Randomized, Controlled Trial With 5-year Follow up

Adverse events reported by the patients were noted at each follow-up visit, including severity, duration, and need for additional therapy. All events due to PDT were described as phototoxic reactions(e.g erythema, burning sensation, swelling, bleeding)

The response was classified as either complete response (complete disappearance of the lesion) or incomplete response (incomplete disappearance of the lesion)

In all cases of complete response, the patients were reviewed at 60 months to check for recurrence. Post-therapy punch biopsies were performed when there was doubt concerning incomplete-response and clinical recurrence

The overall cosmetic outcome was assessed by each investigator for all lesions that achieved complete response at 60 months, and was graded using a 4-point scale: excellent (only slight occurrence of redness or change in pigmentation), good (moderate redness or change in pigmentation), fair (slight to moderate scarring, atrophy, or induration), or poor (extensive scarring, atrophy, or induration)

Dong-A University

Associate professor

Skin and Connective Tissue Diseases

Keratosis, Actinic

Keratosis

Skin Diseases

Precancerous Conditions

Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid).

One single Photodynamic therapy (PDT).

Combination Product: Photodynamic therapy (PDT) using BF-RhodoLED® (ALA-PDT, Ameluz®-PDT).

BF-200 ALA and red light LED lamp

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 (PpIX) during photodynamic therapy with 3 tubes of BF-200 ALA 10% gel (Ameluz®) in combination with the BF-RhodoLED® lamp in the systemic circulation of diseased individuals presenting with actinic keratosis (AK) on the face/scalp or in the periphery (neck/trunk/extremities) along with subjects' safety/tolerability during and after treatment.

Study to Evaluate the Safety of BF-200 ALA (Ameluz®) for Photodynamic Therapy (PDT) in the Treatment of Expanded Fields of Actinic Keratosis (AK)

An Open-label Phase I Study to Evaluate the Pharmacokinetics of 5-aminolevulinic Acid and Protoporphyrin IX in Human Plasma Under Maximal Use Conditions After Topical Application of 3 Tubes of BF-200 ALA 10% Gel for Photodynamic Therapy (PDT) in Subjects Suffering From Actinic Keratosis

Blood samples for ALA analysis for each subject were collected, starting at Visit 1 and then 0.5h prior to BF-200 ALA application for up to 10h afterwards. The concentrations of ALA in plasma were measured by an analytical laboratory using validated, internally standardized liquid chromatography-tandem mass spectrometry methods.

Blood samples for PpIX analysis for each subject were collected, starting at Visit 1 and then 0.5h prior to BF-200 ALA application for up to 10h afterwards. The concentrations of PpIX in plasma were measured by an analytical laboratory using validated, internally standardized liquid chromatography-tandem mass spectrometry methods.

Parameter: AUC(0-t) (Area Under Curve); area under the baseline-adjusted plasma concentration-time curve from time zero to the last sampling time point at which the concentration was at or above lower limit of quantification; t(last) is defined as the last value \>0 after baseline adjustment.

Parameter: AUC(0-∞) (Area Under Curve); area under the baseline-adjusted plasma concentration-time data extrapolated to infinity

Parameter: %AUC(t-∞) (Area Under Curve); proportion of extrapolated part

Parameter: Cmax (Maximum Plasma Concentration); observed maximum baseline-adjusted plasma concentration

Parameter: λz (Elimination Rate Constant); λz denotes the terminal rate constant estimated by linear regression analysis from a range of concentrations in the terminal phase estimated for each treatment and subject by log-linear regression from the linear portion of the logarithmic transformed concentration-time plot. The algorithm will start with the last 3 points with quantifiable concentrations and increases the number of involved points by 1 until the time point after Cmax restricted on time points after removing of the BF-200 ALA gel (all PK samples after the gel is wiped off \[after 3h±10 min); λz was only determined in subjects in which the log-linear terminal phase could clearly be defined. Resulting unreliable parameters were flagged accordingly and not used in descriptive statistics. If any pharmacokinetic parameter should have been classified as unreliable, all calculations that use this parameter were considered missing.

Parameter: t1/2 (apparent terminal half-life); calculated by ln2/λz; t1/2 was only determined in subjects in which the log-linear terminal phase could clearly be defined. Resulting unreliable parameters were flagged accordingly and not used in descriptive statistics. If any pharmacokinetic parameter should have been classified as unreliable, all calculations that use this parameter were considered missing.

Frequency of treatment-emergent adverse events (TEAEs),including serious adverse events (SAEs).

Assessment of pain at the application site using an 11-point Numeric Rating Scale (NRS-11) ranging from 0 (no pain) to 10 (worst imaginable pain)

Application site reactions: discomfort (burning, pain, itching, stinging, warmth, others)

Application site reactions: skin reactions (erythema, edema, induration, vesicles, erosion, ulceration, scaling/flaking, scabbing/crusting, discharge/exudate, others); maximum severity of AE: mild, moderate, or severe

Biofrontera Bioscience GmbH

TEAEs (treatment emergent adverse events) are defined as all AEs or SAEs that occurred after lesion preparation at Visit 2, which was at maximum one hour before IMP application (i.e. AE onset date/time ≥ date/time of IMP application (Visit 2) - 1 h).

• Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid) • Each subject received three entire tubes of the IMP (2 g each, containing 156 mg ALA), resulting in a total dose of 468 mg ALA (free base) • The amount was sufficient to cover one treatment field (continuous field or discontinuous field with several patches), totaling approx. 60 cm² with BF-200 ALA gel at a thickness of approx. 1 mm • Treatment field(s) could be located on either the face/scalp or in the periphery (neck/trunk/extremities) excluding the genitalia (minimal distance of about 1 cm) • IMP dried for approx. 10 min • Subjects had to stay in a well-tempered environment during 3h incubation under light-blocking, occlusive dressing • Dressing was removed; remnant gel wiped off • Illumination with BF-RhodoLED® (10 min; 37 J/cm²) • In case of discontinuous treatment field(s), two BF-RhodoLED® lamps were used simultaneously • One single PDT was performed

Stratum: Face/Scalp

Stratum: Periphery

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Subjects' skin type was assessed at the screening visit using a six-level Fitzpatrick Skin Type Rating Scale, which ranges from very fair (skin type I) to very dark (skin type VI).

Fitzpatrick skin type

Clinical Trial Department

0.5h

1.5h

2.5h

3.5h

ALA Pharmacokinetic Set (PKS ALA): includes all subjects who had at least one evaluable pre-dose and post-dose pharmacokinetic sample (i.e., samples taken after the application of BF-200 ALA); a pre-dose/post-dose sample was regarded evaluable if the plasma concentration was at or above LLOQ.

Assessment of Baseline-adjusted Plasma Concentration-time Curves for ALA After a Single PDT Treatment Applying 3 Tubes of BF-200 ALA in Conjunction With the BF-RhodoLED® Under Maximal Use Conditions in Subjects With Mild to Severe Actinic Keratosis.

PpIX Pharmacokinetic Set (PKS PpIX): includes all subjects who had at least one evaluable pre-dose and post-dose pharmacokinetic sample (i.e., samples taken after the application of BF-200 ALA); a pre-dose/post-dose sample was regarded evaluable if the plasma concentration was at or above LLOQ.

Assessment of Baseline-adjusted Plasma Concentration-time Curves for PpIX After a Single PDT Treatment Applying 3 Tubes of BF-200 ALA in Conjunction With the BF-RhodoLED® Under Maximal Use Conditions in Subjects With Mild to Severe Actinic Keratosis.

Evaluation of Baseline-adjusted Pharmacokinetic Parameters of ALA.

Evaluation of Baseline-adjusted Pharmacokinetic Parameters of PpIX.

Application site erythema

Application site exfoliation

Application site hyperaesthesia

Application site induration

Application site oedema

Application site pain

Application site paraesthesia

Application site pruritus

Application site scab

Application site vesicles

Application site warmth

Safety analysis set (SAF): includes all subjects who underwent at least one of the following treatment procedures: preparation of the treatment field(s), application of BF-200 ALA, or illumination. If the conduct of any treatment procedures was not certain, the subject was to be included in the SAF.

Assessment of the Frequency and Severity of All Treatment-emergent Adverse Events (TEAEs), Including Serious Adverse Events (SAEs) in Response to PDT With BF-200 ALA Under Maximal Use Conditions.

Assessment of Pain Intensity at the Application Site in Response to PDT With BF-200 ALA Under Maximal Use Conditions Using an 11-point Numeric Rating Scale (NRS-11), Where a Score of 0 Means "no Pain" and a Score of 10 Means "Worst Imaginable Pain".

Burning

Itching

Other

Pain

Pain during PDT

Stinging

Warmth

Assessment of Frequency and Severity of Application Site Discomfort in Response to PDT With BF-200 ALA Under Maximal Use Conditions.

Discharge/exudate

Oedema

Erythema

Induration

Scabbing/crusting

Scaling/flaking

Assessment of Frequency and Severity of Application Site Skin Reactions in Response to PDT With BF-200 ALA Under Maximal Use Conditions.

BF-200 ALA (Stratum Face/Scalp and Stratum Periphery)

Overall Study

Standard PDT using topical aminolevulinate followed by red light illumination for actinic keratosis. A region of interest (ROI) on the skin of the arms, hands, legs, or feet will be selected for monitoring. This ROI will be marked and baseline measurements will be taken. The topical drug Levulan (ALA) will be applied to the ROI and other areas being treated, and covered with plastic wrap. Prior to red light illumination, post topical measurements and baseline values will be performed to measure PpIX and sO2. Red light illumination will follow, and sO2 phosphorescence will be recorded continuously from the ROI. After, a post-PpIX measurement will be taken.

Topical Levulan Kerastick is applied to actinic keratoses.

Topical Aminolevulinate

PDT is a technique that combines a photosensitizing drug and an intense light source to kill tumor cells.

Photodynamic therapy (PDT)

To occur post-PTD; used for activation of ALA during photodynamic therapy.

Red light illumination

Edward Maytin, MD, PhD

The purpose of the study is to test a new video device for actinic keratoses. The device takes images of your skin lesions during the treatment, to learn whether this device can predict how well the treatment is working.

This intervention is designed to help establish what the optimal conditions are for treating actinic keratoses with photodynamic therapy (PDT). The primary outcome of this study is to determine whether the rate of singlet oxygen (sO2) production and/or the initial intralesional photosensitize (PpIX) levels, can predict the clinical responsiveness of AK lesions to PDT. Participants will receive standard red light PDT treatment, except that lesions will be carefully counted beforehand. During the window of red light illumination, photos and a video of one area of skin will be taken to allow us to monitor the progress of the treatment. Any remaining lesions will be counted upon follow-up.

Imaging Techniques to Monitor Photosensitizer and sO2 Levels During Photodynamic Therapy of Actinic Keratoses

Noninvasive Imaging Techniques to Monitor Photosensitizer and Singlet Oxygen Levels During Photodynamic Therapy of Actinic Keratoses

All IPD that underlie results in publication

Based on the rate of sO2 production, and/or the initial level of PpIX, is significantly correlated with the clinical responsiveness of AK lesions to PDT treatment. The clinical responsiveness will be measured by the decrease in the number of lesions

To determine whether the initial level of PpIX can predict the clinical responsiveness of AK lesions to PDT treatment. The clinical responsiveness will be measured by the change in PpIX value before and after red light illumination.

To determine whether the rate of sO2 production can predict the clinical responsiveness of AK lesions to PDT treatment. The clinical responsiveness will be measured by the change in sO2 value before and after red light illumination.

To characterize the variability in PpIX production between similarly-sized lesions. This will be measured by the accumulation of PpIX.

To characterize the variability in sO2 generation between similarly-sized lesions, and to test whether production of sO2 during PDT correlates with the amount of photosensitizer available in AK lesions. This will be measured by sO2 production, measured in real-time by sO2 dosimeter.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Long-term Efficacy of Ablative Fractional Laser-assisted Photodynamic Therapy for Treatment of Lower Extremity Bowen's Disease	NCT03320447	Bowen's Disease	lidocaine-prilo... 2940-nm Er:YAG ... methyl-aminolev... Illuminating us...	42 Years - 89 Years	Dong-A University
Study to Evaluate the Safety of BF-200 ALA (Ameluz®) for Photodynamic Therapy (PDT) in the Treatment of Expanded Fields of Actinic Keratosis (AK)	NCT04319159	Actinic Keratos...	BF-200 ALA and ...	18 Years - 85 Years	Biofrontera Bioscience GmbH
Imaging Techniques to Monitor Photosensitizer and sO2 Levels During Photodynamic Therapy of Actinic Keratoses	NCT05923060	Actinic Keratos...	Topical Aminole... Photodynamic th... Red light illum...	18 Years -	Case Comprehensive Cancer Center

Spots Global Cancer Trial Database for protoporphyrin ix