Actinic KeratosesPhase 1NCT04319159

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

A Phase 1 study testing BF-200 ALA and red light LED lamp in people with Actinic Keratoses, run by Biofrontera Bioscience GmbH at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 85 years
Conditions the study is for: Actinic Keratoses
What is being tested?: BF-200 ALA and red light LED lamp
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 48 participants
Where: 1 siteUnited States
Study dates: 5 Mar 2020to 7 Oct 2020
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subjects with at least 12 distinctive and clinically confirmed mild to severe AK lesions (according to Olsen et al. 1991 (37)) with a diameter of ≥ 4 mm each, on either the face/scalp (including forehead, excluding eyes, nostrils, ears, and mouth) or the neck/trunk/extremities, within treatment field(s) of about 60 cm² in total. Treatment field(s) may be discontinuous but must be within 2 illumination areas of the BF-RhodoLED® lamp (6 cm x 16 cm each).
All genders 18-85 years of age (inclusive).
Willingness and ability of the subject to provide informed consent and to sign the Health Insurance Portability and Accountability Act (HIPAA) form. A study-specific informed consent form and HIPAA form must be obtained in writing for all subjects prior to starting any study procedures.
Willingness and ability to comply with study procedures, particularly willingness to receive one PDT with up to two illumination devices simultaneously.
Subjects with good general health and subjects with clinically stable medical conditions will be permitted to be included in the study.
Subjects receiving any drugs affecting coagulation (e.g. anticoagulants, anti-platelet drugs) should be on a stable dose.
Acceptance to abstain from extensive sunbathing and the use of solarium during the clinical study.
Women of child-bearing potential must have a negative serum pregnancy test and must use an adequate and highly effective or two effective methods of contraception throughout the study.

Who cannot join

Any known history of hypersensitivity to ALA, porphyrins or excipients of BF- 200 ALA.
History of soy or peanut allergy.
Subjects with sunburn within illumination areas (reassessment of subjects is allowed once if the sunburn is expected to resolve within the screening period. Reassessment can be done on the day of the actual treatment.).
Clinically significant medical conditions making implementation of the protocol or interpretation of the study results difficult or impairing subjects' safety such as:
Presence of porphyria or known photodermatoses
Known diagnosis of human immunodeficiency virus (HIV) based on clinical history

Show all 43Show fewer

Metastatic tumor or tumor with high probability of metastasis
Infiltrating skin neoplasia (suspected or known)
Unstable cardiovascular disease (New York Heart Association [NYHA] class III, IV)
Unstable hematologic (including Myelodysplastic syndrome), hepatic, renal, neurologic, or endocrine condition
Unstable collagen-vascular condition
Unstable gastrointestinal condition
Immunosuppressive condition
Presence of clinically significant inherited or acquired coagulation defect
Clinical diagnosis of atopic dermatitis, Bowen's disease, BCC, eczema, psoriasis, rosacea, SCC, other malignant or benign tumors in the treatment field(s), or other possible confounding skin conditions (e.g. wounds, irritations, bleeding or skin infections) within or in close proximity (< 5 cm distance) to treatment field(s). (Reassessment of subjects is allowed once if wounds, irritations, bleeding or skin infections are expected to resolve within the screening period. Reassessment can be done on the day of the actual treatment.)
Presence of strong pigmentation, tattoos or any other abnormality that may impact lesion assessment or light penetration in the treatment field(s).
More than moderate smoker (e.g. > 10 cigarettes/day or equivalent).
Suspicion of drug or alcohol abuse. For the purpose of this study, alcohol abuse is defined as more than moderate alcohol consumption (> 1 drink/day for women and > 2 drinks/day for men).
Physical treatment of malignant or benign tumors of the skin within the treatment field(s) and at a distance of < 5 cm to the treatment field(s) during the last 4 weeks prior to screening.
Any therapy such as cryotherapy, laser therapy, electrodessication, surgical removal of lesions, curettage, or treatment with chemical peels such as trichloroacetic acid within the treatment field(s), or within a radius less than 5 cm away from the treatment field(s) 4 weeks prior to screening.
Any topical medical treatment of the skin within the designated time period below:
Topical treatment with ALA or methyl-aminolevulinate (MAL) or an investigational drug in- and outside the treatment field(s) within 8 weeks prior to screening.
Topical treatment with immunomodulatory/immunosuppressive antiinflammatory, or cytotoxic agents inside the treatment field(s) or within a radius less than 5 cm away from the treatment field(s) within 8 weeks prior to screening.
Start of topical administration of medication with hypericin or other drugs with phototoxic or photoallergic potential in- and outside the treatment field(s) within 8 weeks prior to screening. Subjects may, however, be eligible if such medication was applied for more than 8 weeks prior to screening visit without evidence of an actual phototoxic/photoallergic reaction.
Any use of the below specified systemic treatments within the designated periods:
Use of cytotoxic drugs within 24 weeks, immunomodulators or immunosuppressive therapies or use of ALA or ALA-esters (e.g. MAL) within 12 weeks, investigational drugs or drugs known to have major organ toxicity within 8 weeks, interferon or corticosteroids (oral or injectable) within 6 weeks prior to screening.
Start of intake of medication with hypericin or systemically-acting drugs with phototoxic or photoallergic potential within 8 weeks prior to screening. Subjects may, however, be eligible if such medication was taken in or applied for more than 8 weeks prior to screening visit without evidence of an actual phototoxic/photoallergic reaction.
Laboratory values outside the reference range that are clinically significant in the opinion of the investigator (e.g., suggesting an unknown disease and requiring further clinical evaluation according to investigator), especially aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (gamma- GT).
Impaired renal function (Glomerular filtration rate below 50 mL/min/1.73m² estimated by Modification of Diet in Renal Disease equation (MDRD)).
Positive test for HIV antibodies, Hepatitis B-virus surface antigen (HBsAg) or positive Anti-hepatitis C-virus antibody (Anti-HCV) test.
Significant blood donation or blood loss (≥ 500 mL) within three months prior to Visit 2.
Breast-feeding women.
Subject unlikely to comply with the protocol, e.g. inability to return for visits, unlikely to complete the study, or inappropriate in the opinion of the investigator.
Prior participation in the study (participation is defined as having been screened).
A member of study site staff or sponsor staff directly involved in the conduct of the protocol or a close relative thereof.
Simultaneous participation in a further clinical study.
Reassessment of subjects is allowed once if sunburn, wounds, irritations, bleeding or skin infections detected at Visit 1 are expected to resolve within the screening period.
Reassessment can be done on the day of the actual treatment.
Dosing day exclusion criteria:
Febrile or infectious illness within 7 days prior to Visit 2.
Subjects with sunburn, wounds, irritations, bleeding or other confounding skin conditions within illumination areas at Visit 2.
Use of topical NSAIDs inside and outside the treatment field(s) or systemic intake of NSAIDs within 7 days prior to Visit 2.
In case a subject meets one of the dosing day exclusion criteria, Visit 2 can be rescheduled once within 14 days. Meeting any of the dosing day exclusion criteria on the rescheduled visit will lead to discontinuation of the trial.

Trial locations and contacts

1 site in 1 country.

United States1 site

DermResearch Inc.
Austin, Texas, 78759

Other trials in United States

About this study

Official title: 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

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.

Conditions: Actinic Keratoses
Being tested: BF-200 ALA and red light LED lamp
Keywords: Actinic keratosis, Photodynamic therapy, 5-aminolevulinic acid, Protoporphyrin IX, Pharmacokinetics
Medical subject headings: Keratosis, Actinic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BF-200 ALA and red light LED lampCombination product
Combination Product: Photodynamic therapy (PDT) using BF-RhodoLED® (ALA-PDT, Ameluz®-PDT).

Study groups in NCT04319159
Study group	Role	What they receive
BF-200 ALA	Experimental	Topical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single Photodynamic therapy (PDT). Receives: Combination Product: BF-200 ALA and red light LED lamp

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
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.
Measured: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
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.
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.
Measured: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)

Secondary outcomes (18)

Evaluation of Baseline-adjusted Pharmacokinetic Parameters of ALA.
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.
Measured: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of ALA.
Parameter: AUC(0-∞) (Area Under Curve); area under the baseline-adjusted plasma concentration-time data extrapolated to infinity
Measured: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of ALA.
Parameter: %AUC(t-∞) (Area Under Curve); proportion of extrapolated part
Measured: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of ALA.
Parameter: Cmax (Maximum Plasma Concentration); observed maximum baseline-adjusted plasma concentration
Measured: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of ALA.
Parameter: Tmax (time to reach Cmax)
Measured: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of ALA.
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.
Measured: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of ALA.
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.
Measured: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of PpIX.
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.
Measured: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of PpIX.
Parameter: AUC(0-∞) (Area Under Curve); area under the baseline-adjusted plasma concentration-time data extrapolated to infinity
Measured: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of PpIX.
Parameter: %AUC(t-∞) (Area Under Curve); proportion of extrapolated part
Measured: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of PpIX.
Parameter: Cmax (Maximum Plasma Concentration); observed maximum baseline-adjusted plasma concentration
Measured: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of PpIX.
Parameter: Tmax (time to reach Cmax)
Measured: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of PpIX.
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.
Measured: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of PpIX.
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.
Measured: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
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.
Frequency of treatment-emergent adverse events (TEAEs),including serious adverse events (SAEs).
Measured: On treatment day until end of study approximately 4 weeks after treatment day (day 0)
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".
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)
Measured: On treatment day until end of study approximately 4 weeks after treatment day (day 0)
Assessment of Frequency and Severity of Application Site Discomfort in Response to PDT With BF-200 ALA Under Maximal Use Conditions.
Application site reactions: discomfort (burning, pain, itching, stinging, warmth, others)
Measured: On treatment day until end of study approximately 4 weeks after treatment day (day 0)
Assessment of Frequency and Severity of Application Site Skin Reactions in Response to PDT With BF-200 ALA Under Maximal Use Conditions.
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
Measured: On treatment day until end of study approximately 4 weeks after treatment day (day 0)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Mar 20207 Oct 2020

First posted24 Mar 2020
Study start5 Mar 2020
Primary completion9 Sep 2020
Study completion7 Oct 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Actinic KeratosesStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 48 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04319159
Sponsor's protocol ID: ALA-AK-CT015
Status last verified: Oct 2021
First submitted: 10 Mar 2020
Last updated: 11 Nov 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: Yes

Publications

Novak B, DuBois J, Chahrour O, Papusha T, Hirt S, Philippi T, Zogel C, Osenberg K, Schmitz B, Lubbert H. Clinical Pharmacokinetics and Safety of a 10% Aminolevulinic Acid Hydrochloride Nanoemulsion Gel (BF-200 ALA) in Photodynamic Therapy of Patients Extensively Affected With Actinic Keratosis: Results of 2 Maximal Usage Pharmacokinetic Trials. Clin Pharmacol Drug Dev. 2022 Apr;11(4):535-550. doi: 10.1002/cpdd.1023. Epub 2021 Oct 11.
PubMed 34633154

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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A Pilot Clinical Trial Comparing Topical Fluorouracil to Fluorouracil Plus Calcipotriene Field Treatments in Patients With Multiple Actinic Keratoses
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Basal Cell Carcinoma Chemoprevention Trial
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Cryotherapy in Combination With Red Light PDT for Actinic Keratosis of Full Face
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All Actinic Keratoses trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT04319159
Acronym / sponsor ID: ALA-AK-CT015
Conditions: Actinic Keratoses
Keywords: Actinic keratosis, Photodynamic therapy, 5-aminolevulinic acid, Protoporphyrin IX, Pharmacokinetics
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 48 participants (actual)
Lead sponsor: Biofrontera Bioscience GmbHIndustry (pharma, biotech, devices)
Study start: 5 Mar 2020 (actual)
Primary completion: 9 Sep 2020 (actual)
Study completion: 7 Oct 2020 (actual)
First posted: 24 Mar 2020 (actual)
Results: Posted 11 Nov 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
BF-200 ALA	Experimental	Combination Product: BF-200 ALA and red light LED lampTopical application of BF-200 ALA containing 7.8% 5-ALA (5-aminolevulinic acid). One single Photodynamic therapy (PDT).

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Subjects with at least 12 distinctive and clinically confirmed mild to severe AK lesions (according to Olsen et al. 1991 (37)) with a diameter of ≥ 4 mm each, on either the face/scalp (including forehead, excluding eyes, nostrils, ears, and mouth) or the neck/trunk/extremities, within treatment field(s) of about 60 cm² in total. Treatment field(s) may be discontinuous but must be within 2 illumination areas of the BF-RhodoLED® lamp (6 cm x 16 cm each).
All genders 18-85 years of age (inclusive).
Willingness and ability of the subject to provide informed consent and to sign the Health Insurance Portability and Accountability Act (HIPAA) form. A study-specific informed consent form and HIPAA form must be obtained in writing for all subjects prior to starting any study procedures.
Willingness and ability to comply with study procedures, particularly willingness to receive one PDT with up to two illumination devices simultaneously.
Subjects with good general health and subjects with clinically stable medical conditions will be permitted to be included in the study.

Key exclusion criteria (43 listed)

Any known history of hypersensitivity to ALA, porphyrins or excipients of BF- 200 ALA.
History of soy or peanut allergy.
Subjects with sunburn within illumination areas (reassessment of subjects is allowed once if the sunburn is expected to resolve within the screening period. Reassessment can be done on the day of the actual treatment.).
Clinically significant medical conditions making implementation of the protocol or interpretation of the study results difficult or impairing subjects' safety such as:
Clinical diagnosis of atopic dermatitis, Bowen's disease, BCC, eczema, psoriasis, rosacea, SCC, other malignant or benign tumors in the treatment field(s), or other possible confounding skin conditions (e.g. wounds, irritations, bleeding or skin infections) within or in close proximity (< 5 cm distance) to treatment field(s). (Reassessment of subjects is allowed once if wounds, irritations, bleeding or skin infections are expected to resolve within the screening period. Reassessment can be done on the day of the actual treatment.)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BF-200 ALA and red light LED lampCombination Product: Photodynamic therapy (PDT) using BF-RhodoLED® (ALA-PDT, Ameluz®-PDT).	Combination product	BF-200 ALA

Primary outcome

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.
Time frame: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
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.
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.
Time frame: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
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.

18 secondary outcomes

Evaluation of Baseline-adjusted Pharmacokinetic Parameters of ALA.
Time frame: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of ALA.
Time frame: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of ALA.
Time frame: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of ALA.
Time frame: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of ALA.
Time frame: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of ALA.
Time frame: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of ALA.
Time frame: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of PpIX.
Time frame: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of PpIX.
Time frame: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of PpIX.
Time frame: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of PpIX.
Time frame: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of PpIX.
Time frame: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of PpIX.
Time frame: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
Evaluation of Baseline-adjusted Pharmacokinetic Parameters of PpIX.
Time frame: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)
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.
Time frame: On treatment day until end of study approximately 4 weeks after treatment day (day 0)
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".
Time frame: On treatment day until end of study approximately 4 weeks after treatment day (day 0)
Assessment of Frequency and Severity of Application Site Discomfort in Response to PDT With BF-200 ALA Under Maximal Use Conditions.
Time frame: On treatment day until end of study approximately 4 weeks after treatment day (day 0)
Assessment of Frequency and Severity of Application Site Skin Reactions in Response to PDT With BF-200 ALA Under Maximal Use Conditions.
Time frame: On treatment day until end of study approximately 4 weeks after treatment day (day 0)

Results and safety

Results posted to the registry on 11 Nov 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
BF-200 ALA (Stratum Face/Scalp and Stratum Periphery)	48	32

Primary outcome: 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.

Time frame: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination). Geometric mean (Standard Deviation). Unit: ng/mL

Measure	Stratum: Face/Scalp n = 16	Stratum: Periphery n = 16
0.5h	8.904 (3.3502)	10.21 (5.2811)
1h	12.45 (3.1865)	9.383 (5.2972)
1.5h	18.96 (2.4231)	10.15 (4.3289)
2h	18.02 (2.7917)	9.561 (6.3130)
2.5h	23.06 (2.1768)	6.233 (5.7572)
3h	24.71 (2.2076)	13.55 (5.3204)
3.5h	22.00 (1.9477)	10.77 (3.3921)
4h	16.54 (1.7954)	7.172 (3.4656)

Population analysed: 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.

Primary outcome: 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.

Time frame: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination). Geometric mean (Standard Deviation). Unit: ng/mL

Measure	Stratum: Face/Scalp n = 15	Stratum: Periphery n = 15
0.5h	0.2820 (2.2288)	0.2199 (3.7060)
1h	0.3078 (1.9993)	0.1957 (2.8664)
1.5h	0.2176 (2.8671)	0.3022 (1.7326)
2h	0.1497 (3.0551)	0.2265 (4.3780)
2.5h	0.1634 (2.2679)	0.3389 (1.8265)
3h	0.1369 (2.5145)	0.1972 (2.2296)
3.5h	0.2313 (1.5809)	0.2334 (3.4067)
4h	0.2021 (2.7651)	0.3522 (3.1629)

Population analysed: 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.

18 secondary outcomes are reported in the full results.

Adverse events

Time frame: On treatment day until end of study approximately 4 weeks after treatment day (07 October 2020, study completion date).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Stratum: Face/Scalp	0 of 16 (0%)	16 of 16 (100%)	0 of 16
Stratum: Periphery	0 of 16 (0%)	16 of 16 (100%)	0 of 16

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34633154Novak B, DuBois J, Chahrour O, Papusha T, Hirt S, Philippi T, Zogel C, Osenberg K, Schmitz B, Lubbert H. Clinical Pharmacokinetics and Safety of a 10% Aminolevulinic Acid Hydrochloride Nanoemulsion Gel (BF-200 ALA) in Photodynamic Therapy of Patients Extensively Affected With Actinic Keratosis: Results of 2 Maximal Usage Pharmacokinetic Trials. Clin Pharmacol Drug Dev. 2022 Apr;11(4):535-550. doi: 10.1002/cpdd.1023. Epub 2021 Oct 11.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BF-200 ALA and red light LED lamp in people with Actinic Keratoses, run by Biofrontera Bioscience GmbH at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: On treatment day (day 0): 0.5, 1, 1.5, 2, 2.5, 3*, 3.5, 4, 5, 6, 8, 10 hours post-dose (*prior to illumination)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04319159, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Nov 2021.