Actinic KeratosisPhase 3NCT02799069
Evaluation of Safety and Efficacy of BF-200 ALA for the Treatment of Actinic Keratosis With Photodynamic Therapy
A Phase 3 study testing BF-200 ALA and MAL Cream in people with Actinic Keratosis, run by Biofrontera Bioscience GmbH.
Trial summary
The aim of the study is to evaluate the non-inferiority of BF-200 ALA (Ameluz) in the treatment of actinic keratosis (AK) with photodynamic therapy (PDT) compared to Metvix. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Actinic Keratosis
- What is being tested?
- BF-200 ALA and MAL Cream
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 571 participants
- Where
- No sites listed yet
- Study dates
- Apr 2008to Aug 2009
- Phase
- Phase 3
- 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
Main Inclusion Criteria:
- Written informed consent.
- Men and women between 18 and 85 years of age.
- 4-8 AK lesions of 0.5 to 1.5 cm diameter of mild to moderate intensity (Olsen grade 1 and 2) in the face and/or on the bald scalp. Lesions on the eyes, nostrils, ears and mouth were not considered for treatment during the planned study.
- Target AK lesions were to be discrete and quantifiable; adjacent AK lesions were to show a minimum distance of 1.0 cm from one another.
- Confirmation of AK by biopsy taken at screening.
- Free of significant physical abnormalities (e.g., tattoos, dermatoses) in the potential treatment region that could have caused difficulty with examination or final evaluation.
- Willingness to stop the use of moisturizers and any other topical treatments within the treatment region.
- Good general health condition.
- Healthy subjects and subjects with clinically stable medical conditions including, but not limited to the following diseases (controlled hypertension, diabetes mellitus type II, hypercholesterolemia, osteoarthritis) were permitted to be included in the study if the medication taken for the treatment of the disease did not match an exclusion criterion or was not specified as prohibited concomitant medication.
- No extensive sunbathing or solarium use during the trial.
- Negative pregnancy test at screening.
Main exclusion criteria:
- Known hypersensitivity to BF-200 ALA, MAL (methyl-aminolevulinic acid) and/or any of the ingredients of the formulations
- Clinically significant medical conditions (tumor disease etc.) making implementation of the protocol or interpretation of the study results difficult
- Presence of photodermatoses
- Presence of other tumors in the treatment areas within the last 4 weeks
- Start of treatment with phototoxic or photoallergic drugs within 8 weeks prior to screening
- Current treatment with immunosuppression therapy
- Hypersensitivity to porphyrins
- Presence of porphyria
- Presence of inherited or acquired coagulation defect
- Any topical treatment within the treatment area within 12 weeks before PDT1 (first PDT Treatment)
- Topical treatment with ALA or MAL outside the treatment area during participation in the study
- None of the specified systemic treatments within the designated period before PDT1
About this study
Official title: A Randomized, Observer Blind, Multinational Phase III Study to Evaluate the Safety and Efficacy of a Nanoemulsion Gel Formulation BF-200 ALA, in Comparison With Metvix® and Placebo, for the Treatment of Actinic Keratosis With PDT
The aim of the study is to evaluate the non-inferiority of BF-200 ALA (Ameluz) in the treatment of actinic keratosis (AK) with photodynamic therapy (PDT) compared to Metvix.
Read the detailed description
This was a randomized, observer-blind, multinational, comparator and placebo-controlled parallel group, (3:3:1 ratio) study to compare the efficacy and safety of BF-200 ALA with the comparator Metvix® (methyl-[5-amino-4-oxopentanoate]) and placebo, for the treatment of AK with PDT.
- Conditions
- Actinic Keratosis
- Being tested
- BF-200 ALA, MAL Cream, Vehicle
- 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 ALADrug
Also called Ameluz
topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
MAL CreamDrug
Also called Metvix, Metvixia
topical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
VehicleDrug
Also called matched placebo to BF-200 ALA gel
topical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source.
| Study group | Role | What they receive |
|---|---|---|
| BF-200 ALA | Active comparator | Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. Receives: Drug: BF-200 ALA |
| MAL Cream | Active comparator | Topical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. Receives: Drug: MAL Cream |
| Vehicle | Placebo comparator | Topical application of matched Placebo to BF-200 ALA gel (without containing active ingredient) ). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. Receives: Drug: Vehicle |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT), ITT
An overall complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) 12 weeks after the last PDT.
The outcome measure considered complete responders who were completely cleared 12 weeks after the first PDT and responders who were completely cleared 12 weeks after the second PDT if a re-treatment was necessary (in case of partial- or non-responding lesions 12 weeks after the first PDT)
Measured: 12 weeks after the last PDT, up to 24 weeks after the first treatment
Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT), PP
An overall complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) 12 weeks after the last PDT.
The outcome measure considered complete responders who were completely cleared 12 weeks after the first PDT and responders who were completely cleared 12 weeks after the second PDT if a re-treatment was necessary (in case of partial- or non-responding lesions 12 weeks after the first PDT)
Measured: 12 weeks after the last PDT, up to 24 weeks after the first treatment
Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT) Illuminated With Narrow Spectrum Devices Only
Subgroup analysis of patients treated with a narrow spectrum device for PDT Illumination (~630 nm).
An overall complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) 12 weeks after the last PDT.
The outcome measure considered complete responders who were completely cleared 12 weeks after the first PDT and responders who were completely cleared 12 weeks after the second PDT if a re-treatment was necessary (in case of partial- or non-responding lesions 12 weeks after the first PDT)
Measured: 12 weeks after the last PDT, up to 24 weeks after the first treatment
Secondary outcomes (32)
Percentage of Participants With Complete Response 3-4 Weeks After First Photodynamic Therapy (PDT)
A complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) at 3-4 weeks after the first PDT.
Measured: 3-4 weeks after the first PDT
Percentage of Participants With Complete Response 12 Weeks After First Photodynamic Therapy (PDT)
A complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) at 12 weeks after the first PDT.
Measured: 12 weeks after the first PDT
Percentage of Participants With Complete Response 3-4 Weeks After the Second Photodynamic Therapy (PDT)
A complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) at 3-4 weeks after the second PDT. A second PDT was applied in case partial- or non-responding lesions remained 12 weeks after the first PDT.
Measured: 3-4 weeks after the second PDT, 15-16 weeks after first treatment
Percentage of Participants With Complete Response 12 Weeks After Second Photodynamic Therapy (PDT)
A complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) at 12 weeks after the second PDT. A second PDT was applied in case partial- or non-responding lesions remained 12 weeks after the first PDT.
Measured: 12 weeks after the second PDT, 24 weeks after first treatment
Percentage of Participants With Complete Response 3-4 Weeks After Last Photodynamic Therapy (PDT)
A complete responder at week 3-4 after treatment was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission). This outcome measure considered patients who were completely cleared at 3-4 weeks after the last PDT which included complete responders 3-4 weeks after the first and complete responders 3-4 weeks after the second PDT ( a second PDT was applied in case of remaining lesions 12 weeks after the first PDT).
Measured: 3-4 weeks after the last PDT, up to 16 weeks after the first treatment
Percentage of Participants With Partial Response at 3-4 Weeks After First Photodynamic Therapy (PDT)
A partial responder was defined as a subject in whom at least 75% of the treated lesions were cleared (lesions showing complete remission). This outcome measure considers partial responders at 3-4 weeks after the first PDT.
Measured: 3-4 weeks after the first PDT
Percentage of Participants With Partial Response at 12 Weeks After the First Photodynamic Therapy (PDT)
A partial responder was defined as a subject in whom at least 75% of the treated lesions were cleared (lesions showing complete remission). This outcome measure considers partial responders at 12 weeks after the first PDT.
Measured: 12 weeks after the first PDT
Percentage of Participants With Partial Response at 3-4 Weeks After the Second Photodynamic Therapy (PDT)
A partial responder was defined as a subject in whom at least 75% of the treated lesions were cleared (lesions showing complete remission). This outcome measure considers partial responders at 3-4 weeks after the second PDT.
A second PDT was applied in case of partial- or non-responding lesions 12 weeks after the first PDT.
Measured: 3-4 weeks after the second PDT, 15-16 weeks after first treatment
Percentage of Participants With Partial Response at 12 Weeks After the Second Photodynamic Therapy (PDT)
A partial responder was defined as a subject in whom at least 75% of the treated lesions were cleared (lesions showing complete remission). This outcome measure considers partial responders at 12 weeks after the second PDT.
A second PDT was applied in case of partial- or non-responding lesions 12 weeks after the first PDT.
Measured: 12 weeks after the second PDT, 24 weeks after first treatment
Percentage of Participants With Partial Response at 3-4 Weeks After Last Photodynamic Therapy (PDT)
A partial responder was defined as a subject in whom at least 75% of the treated lesions were cleared (lesions showing complete remission). This outcome measure considers partial responders at 3-4 weeks after last PDT.
The outcome measure combined partial responders with at least 75% of lesions cleared at 3-4 weeks after the first PDT or after the second PDT (a second PDT was applied in case of partial- or non-responding lesions 12 weeks after the first PDT).
Measured: 3-4 weeks after the last PDT, up to 16 weeks after the first treatment
Percentage of Participants With Partial Response at 12 Weeks After Last Photodynamic Therapy (PDT)
A partial responder was defined as a subject in whom at least 75% of the treated lesions were cleared (lesions showing complete remission). This outcome measure considers partial responders at 12 weeks after last PDT.
The outcome measure combined partial responders with at least 75% of lesions cleared at 12 weeks after the first PDT and after the second PDT (a second PDT was applied in case of partial- or non-responding lesions 12 weeks after the first PDT) .
Measured: 12 weeks after the last PDT, up to 24 weeks after first treatment
Complete Lesion Response Rate 3-4 Weeks After First Photodynamic Therapy (PDT)
Completely cleared individual lesions as defined at 3-4 weeks after first photodynamic therapy (PDT)
Measured: 3-4 weeks after the first PDT
Complete Lesion Response Rate 12 Weeks After First Photodynamic Therapy (PDT)
Completely cleared individual lesions as defined at 12 weeks after the first photodynamic therapy (PDT).
Measured: 12 weeks after the first PDT
Complete Lesion Response Rate 3-4 Weeks After the Second Photodynamic Therapy (PDT)
Completely cleared individual lesions as defined at 3-4 weeks after the second PDT. A second PDT was applied in case the individual lesion showed no or partial response12 weeks after first PDT.
Measured: 3-4 weeks after the second PDT, 15-16 weeks after first treatment
Complete Lesion Response Rate 12 Weeks After Second PDT
Completely cleared individual lesions as defined at 12 weeks after second PDT. A second PDT was applied in case the individual lesion showed no or partial response 12 weeks after first PDT.
Measured: 12 weeks after the second PDT, 24 weeks after first treatment
Complete Lesion Response Rate 3-4 Weeks After Last Photodynamic Therapy (PDT)
Completely cleared individual lesions defined at 3-4 weeks after the last PDT comprising of completely cleared individual lesions 3-4 weeks after the first and after the second PDT (a second PDT was applied in case lesions show no or partial response 12 weeks after the first PDT).
Measured: 3-4 weeks after the last PDT, up to 16 weeks after first treatment
Complete Lesion Response Rate 12 Weeks After Last Photodynamic Therapy (PDT)
Completely cleared individual lesions 12 weeks after last PDT comprising of completely cleared individual lesions 12 weeks after the first or second PDT (a second PDT was applied in case individual lesions show no or partial response 12 weeks after first PDT).
Measured: 12 weeks after the last PDT, up to 24 weeks after first treatment
Complete Lesion Response Rates 12 Weeks After Last Photodynamic Therapy (PDT) Illuminated With Narrow Spectrum Devices Only
Completely cleared individual lesions 12 weeks after last PDT comprising of individual cleared lesions 12 weeks after the first or second PDT. A second PDT was applied in case individual lesion showed no or partial response 12 weeks after the first PDT.
Lesions were illuminated during photodynamic therapy with narrow spectrum devices only (~630 nm).
Measured: up to 12 weeks after the last PDT, up to 24 weeks after first treatment
Change From Baseline in Total Lesion Area 3-4 Weeks After the First Photodynamic Therapy (PDT)
Percentage of change from baseline in the lesion area of all treated lesions per subject (summation of sizes of all treated lesions) assessed at 3-4 weeks after the first PDT.
Measured: 3-4 weeks after the first PDT
Change From Baseline in Total Lesion Area 12 Weeks After the First Photodynamic Therapy (PDT)
the change from baseline in the lesion area of all treated lesions per subject (summation of sizes of all treated lesions) assessed 12 weeks after the first PDT.
Measured: 12 weeks after the first PDT
Change From Baseline in Total Lesion Area 3-4 Weeks After the Second Photodynamic Therapy (PDT)
the change from baseline in the lesion area of all treated lesions per subject (summation of sizes of all treated lesions) assessed 3-4 weeks after the second PDT. A second PDT was applied in case of non or partially responding lesions 12 weeks after first PDT.
Measured: 3-4 weeks after the second PDT, 15-16 weeks after first treatment
Change From Baseline in Total Lesion Area 12 Weeks After Second Photodynamic Therapy (PDT)
the change from baseline in the lesion area of all treated lesions per subject (summation of sizes of all treated lesions) assessed 12 weeks after the second PDT. A second PDT was applied in case of non- or partially responding lesions 12 weeks after first PDT.
Measured: 12 weeks after the second PDT, 24 after first treatment
Change From Baseline in Total Lesion Area 3-4 Weeks After Last Photodynamic Therapy (PDT)
the change from baseline in the lesion area of all treated lesions per subject (summation of sizes of all treated lesions) assessed at 3-4 weeks after last PDT, combining the changes from baseline in total lesion area of subjects 3-4 weeks after first PDT and second PDT (a second PDT was applied for subjects who showed non- or partially responding lesions 12 weeks after the first PDT).
Measured: 3-4 weeks after the last PDT, up to 16 weeks after the first treatment
Change From Baseline in Total Lesion Area 12 Weeks After Last Photodynamic Therapy (PDT)
the change from baseline in the lesion area of all treated lesions per subject (summation of sizes of all treated lesions) assessed at 12 weeks after last PDT, combining the changes from baseline in total lesion area at 12 weeks after the first PDT and at 12 weeks after the second PDT (a second PDT was applied to subjects with non- or partially responding lesions 12 weeks after the first PDT).
Measured: 12 weeks after the last PDT, up to 24 weeks after the first treatment
Overall Cosmetic Outcome of the Treated Skin 12 Weeks After Last Photodynamic Therapy (PDT) Compared to Baseline
The cosmetic outcome 12 weeks after the last PDT (12 weeks after 1st PDT for subjects who are completely cleared at this time point, 12 weeks after 2nd PDT for subjects retreated due to remaining lesions 12 weeks after 1st PDT) will be calculated on the basis of the skin quality assessment (skin surface, hyperpigmentation, hypopigmentation, mottled or irregular pigmentation, degree of scarring, and atrophy) upon visual examination (scale: 0= none, 1= mild, 2= moderate, 3=severe). The cosmetic outcome is rated as very good if the sum score of the previously mentioned ratings (all ratings for each sign added up) has improved by at least 2 points as compared to baseline; as good if the sum score has improved by at least 1 point as compared to baseline; as satisfactory if the sum score is identical to the one at baseline; as unsatisfactory if the sum score has worsened by 1 point compared to baseline and as impaired if the sum score has worsened by at least 2 points compared to baseline.
Measured: 12 weeks after the last PDT, up to 24 weeks after first treatment
Local Skin Reactions During First Photodynamic Therapy (PDT-1)
Local skin reactions in the treatment area as assessed by the investigator during the first PDT (PDT-1)
Measured: during PDT treatment [3 h - 4 h ]
Local Skin Reactions During Second Photodynamic Therapy (PDT-2) for Retreated Subjects
Local skin reactions in the treatment area as assessed by the investigator during PDT-2; only applicable for subjects who were retreated with a second PDT due to remaining lesions 12 weeks after the first PDT (subjects with data).
Measured: during PDT treatment [3 h - 4 h ]
Local Discomfort During First Photodynamic Therapy (PDT-1)
Local discomfort reported by the patients during Illumination of first PDT (PDT1)
Measured: during PDT treatment [3 h - 4 h ]
Local Discomfort During Second Photodynamic Therapy (PDT-2) for Retreated Subjects
Local discomfort reported by the patients during Illumination phase of retreatment (PDT-2); only applicable for subjects who received a retreatment (PDT-2) due to remaining lesions 12 weeks after the first treatment (PDT-1) (subjects with data)
Measured: during PDT treatment [3 h - 4 h ]
Local Discomfort - Pain During First Photodynamic Therapy (PDT-1)
Pain (11-point numeric rating scale) by PDT Session; Overall (If both areas have been treated, maximum intensity over both areas is used for analysis.) Patients assessed the pain experienced during PDT using an 11-point numeric rating pain scale (NRPS) ranging from 0 (no pain at all) to 10 (worst possible pain). This score reflects the patient's maximum pain during PDT. This outcome measure shows pain score after the first PDT.
Measured: during PDT treatment [3 h - 4 h ]
Local Discomfort - Pain During Second Photodynamic Therapy (PDT-2) for Retreated Subjects
Pain (11-point numeric rating scale) by PDT Session; Overall (If both areas have been treated, maximum intensity over both areas is used for analysis.) Patients assessed the pain experienced during PDT using an 11-point numeric rating pain scale (NRPS) ranging from 0 (no pain at all) to 10 (worst possible pain). This score reflects the patient's maximum pain during PDT.
Only applicable for subjects who received a retreatment (PDT-2) due to remaining lesions 12 weeks after the first treatment (PDT-1) (subjects with data)
Measured: during PDT treatment [3 h - 4 h ]
Adverse Reactions
Adverse reactions are Treatment-Emergent Adverse Events considered at least possibly related to the treatment with the randomized investigational medicinal products; Adverse reactions are shown with a frequency cut off of >=5%.
TEAEs are considered from subjects who received only one PDT or subjects who received 2 PDTs (initial Treatment (PDT-1) and retreatment (PDT-2) due to remaining lesions 12 weeks after first photodynamic therapy.
The safety set consists of all patients treated at least once with investigational product. Treatment with investigational product consists of application of study drug followed by illumination. This excludes one patient from the safety set; for this patient the investigational product was applied on the skin but it was not illuminated. Patients are treated according to actual treatment.
Measured: up to 12 weeks after the last PDT, up to 24 weeks after first treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2016 (estimated)
- Study startApr 2008
- Primary completionAug 2009
- Study completionAug 2009
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 (2)Papers the sponsor has linked to this study.
- Other trials for Actinic KeratosisStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 571 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biofrontera Bioscience GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Accovion GmbH
- Responsible party
- Sponsor
- Investigators
- Thomas Dirschka, Prof. Dr., Principal investigator, Akademische Lehrpraxis der Universität Witten-Herdecke Heinz-Fangman-Straße 57 42287 Wuppertal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02799069
- Sponsor's protocol ID
- ALA-AK-CT002
- Status last verified
- Mar 2017
- First submitted
- 26 May 2016
- Last updated
- 28 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Dirschka T, Radny P, Dominicus R, Mensing H, Bruning H, Jenne L, Karl L, Sebastian M, Oster-Schmidt C, Klovekorn W, Reinhold U, Tanner M, Grone D, Deichmann M, Simon M, Hubinger F, Hofbauer G, Krahn-Senftleben G, Borrosch F, Reich K, Berking C, Wolf P, Lehmann P, Moers-Carpi M, Honigsmann H, Wernicke-Panten K, Helwig C, Foguet M, Schmitz B, Lubbert H, Szeimies RM; AK-CT002 Study Group. 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. Br J Dermatol. 2012 Jan;166(1):137-46. doi: 10.1111/j.1365-2133.2011.10613.x. Epub 2011 Dec 21.
PubMed 21910711Dirschka T, Radny P, Dominicus R, Mensing H, Bruning H, Jenne L, Karl L, Sebastian M, Oster-Schmidt C, Klovekorn W, Reinhold U, Tanner M, Grone D, Deichmann M, Simon M, Hubinger F, Hofbauer G, Krahn-Senftleben G, Borrosch F, Reich K, Berking C, Wolf P, Lehmann P, Moers-Carpi M, Honigsmann H, Wernicke-Panten K, Hahn S, Pabst G, Voss D, Foguet M, Schmitz B, Lubbert H, Szeimies RM; AK-CT002 Study Group; AK-CT003 Study Group. 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. Br J Dermatol. 2013 Apr;168(4):825-36. doi: 10.1111/bjd.12158.
PubMed 23252768
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Observer Blind, Multinational Phase III Study to Evaluate the Safety and Efficacy of a Nanoemulsion Gel Formulation BF-200 ALA, in Comparison With Metvix® and Placebo, for the Treatment of Actinic Keratosis With PDT
- ClinicalTrials.gov ID
- NCT02799069
- Acronym / sponsor ID
- ALA-AK-CT002
- Conditions
- Actinic Keratosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 571 participants (actual)
- Lead sponsor
- Biofrontera Bioscience GmbHIndustry (pharma, biotech, devices)
- Collaborators
- Accovion GmbH
- Study start
- Apr 2008
- Primary completion
- Aug 2009 (actual)
- Study completion
- Aug 2009 (actual)
- First posted
- 14 Jun 2016 (estimated)
- Results
- Posted 23 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to evaluate the non-inferiority of BF-200 ALA (Ameluz) in the treatment of actinic keratosis (AK) with photodynamic therapy (PDT) compared to Metvix.
Detailed description
This was a randomized, observer-blind, multinational, comparator and placebo-controlled parallel group, (3:3:1 ratio) study to compare the efficacy and safety of BF-200 ALA with the comparator Metvix® (methyl-[5-amino-4-oxopentanoate]) and placebo, for the treatment of AK with PDT.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| BF-200 ALA | Active comparator | Drug: BF-200 ALATopical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid (ALA). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. |
| MAL Cream | Active comparator | Drug: MAL CreamTopical application of MAL cream (Metvix) containing 160 mg/g methyl-aminolevulinate (MAL). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. |
| Vehicle | Placebo comparator | Drug: VehicleTopical application of matched Placebo to BF-200 ALA gel (without containing active ingredient) ). Application of a 1 mm thick layer covering each lesion and a 0.5 cm to 1 cm surrounding margin. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 ALAAlso: Ameluztopical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source. | Drug | BF-200 ALA |
| MAL CreamAlso: Metvix, Metvixiatopical treatment for photodynamic therapy combining drug application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source. | Drug | MAL Cream |
| VehicleAlso: matched placebo to BF-200 ALA geltopical treatment for photodynamic therapy combining vehicle application and after a 3 h incubation subsequent illumination with a broad or narrow spectrum light source. | Drug | Vehicle |
Primary outcome
Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT), ITT
Time frame: 12 weeks after the last PDT, up to 24 weeks after the first treatment
An overall complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) 12 weeks after the last PDT. The outcome measure considered complete responders who were completely cleared 12 weeks after the first PDT and responders who were completely cleared 12 weeks after the second PDT if a re-treatment was necessary (in case of partial- or non-responding lesions 12 weeks after the first PDT)
Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT), PP
Time frame: 12 weeks after the last PDT, up to 24 weeks after the first treatment
An overall complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) 12 weeks after the last PDT. The outcome measure considered complete responders who were completely cleared 12 weeks after the first PDT and responders who were completely cleared 12 weeks after the second PDT if a re-treatment was necessary (in case of partial- or non-responding lesions 12 weeks after the first PDT)
Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT) Illuminated With Narrow Spectrum Devices Only
Time frame: 12 weeks after the last PDT, up to 24 weeks after the first treatment
Subgroup analysis of patients treated with a narrow spectrum device for PDT Illumination (~630 nm). An overall complete responder was defined as a subject in whom all treated lesions were cleared (all lesions showing complete remission) 12 weeks after the last PDT. The outcome measure considered complete responders who were completely cleared 12 weeks after the first PDT and responders who were completely cleared 12 weeks after the second PDT if a re-treatment was necessary (in case of partial- or non-responding lesions 12 weeks after the first PDT)
32 secondary outcomes
Percentage of Participants With Complete Response 3-4 Weeks After First Photodynamic Therapy (PDT)
Time frame: 3-4 weeks after the first PDT
Percentage of Participants With Complete Response 12 Weeks After First Photodynamic Therapy (PDT)
Time frame: 12 weeks after the first PDT
Percentage of Participants With Complete Response 3-4 Weeks After the Second Photodynamic Therapy (PDT)
Time frame: 3-4 weeks after the second PDT, 15-16 weeks after first treatment
Percentage of Participants With Complete Response 12 Weeks After Second Photodynamic Therapy (PDT)
Time frame: 12 weeks after the second PDT, 24 weeks after first treatment
Percentage of Participants With Complete Response 3-4 Weeks After Last Photodynamic Therapy (PDT)
Time frame: 3-4 weeks after the last PDT, up to 16 weeks after the first treatment
Percentage of Participants With Partial Response at 3-4 Weeks After First Photodynamic Therapy (PDT)
Time frame: 3-4 weeks after the first PDT
Percentage of Participants With Partial Response at 12 Weeks After the First Photodynamic Therapy (PDT)
Time frame: 12 weeks after the first PDT
Percentage of Participants With Partial Response at 3-4 Weeks After the Second Photodynamic Therapy (PDT)
Time frame: 3-4 weeks after the second PDT, 15-16 weeks after first treatment
Percentage of Participants With Partial Response at 12 Weeks After the Second Photodynamic Therapy (PDT)
Time frame: 12 weeks after the second PDT, 24 weeks after first treatment
Percentage of Participants With Partial Response at 3-4 Weeks After Last Photodynamic Therapy (PDT)
Time frame: 3-4 weeks after the last PDT, up to 16 weeks after the first treatment
Percentage of Participants With Partial Response at 12 Weeks After Last Photodynamic Therapy (PDT)
Time frame: 12 weeks after the last PDT, up to 24 weeks after first treatment
Complete Lesion Response Rate 3-4 Weeks After First Photodynamic Therapy (PDT)
Time frame: 3-4 weeks after the first PDT
Complete Lesion Response Rate 12 Weeks After First Photodynamic Therapy (PDT)
Time frame: 12 weeks after the first PDT
Complete Lesion Response Rate 3-4 Weeks After the Second Photodynamic Therapy (PDT)
Time frame: 3-4 weeks after the second PDT, 15-16 weeks after first treatment
Complete Lesion Response Rate 12 Weeks After Second PDT
Time frame: 12 weeks after the second PDT, 24 weeks after first treatment
Complete Lesion Response Rate 3-4 Weeks After Last Photodynamic Therapy (PDT)
Time frame: 3-4 weeks after the last PDT, up to 16 weeks after first treatment
Complete Lesion Response Rate 12 Weeks After Last Photodynamic Therapy (PDT)
Time frame: 12 weeks after the last PDT, up to 24 weeks after first treatment
Complete Lesion Response Rates 12 Weeks After Last Photodynamic Therapy (PDT) Illuminated With Narrow Spectrum Devices Only
Time frame: up to 12 weeks after the last PDT, up to 24 weeks after first treatment
Change From Baseline in Total Lesion Area 3-4 Weeks After the First Photodynamic Therapy (PDT)
Time frame: 3-4 weeks after the first PDT
Change From Baseline in Total Lesion Area 12 Weeks After the First Photodynamic Therapy (PDT)
Time frame: 12 weeks after the first PDT
Change From Baseline in Total Lesion Area 3-4 Weeks After the Second Photodynamic Therapy (PDT)
Time frame: 3-4 weeks after the second PDT, 15-16 weeks after first treatment
Change From Baseline in Total Lesion Area 12 Weeks After Second Photodynamic Therapy (PDT)
Time frame: 12 weeks after the second PDT, 24 after first treatment
Change From Baseline in Total Lesion Area 3-4 Weeks After Last Photodynamic Therapy (PDT)
Time frame: 3-4 weeks after the last PDT, up to 16 weeks after the first treatment
Change From Baseline in Total Lesion Area 12 Weeks After Last Photodynamic Therapy (PDT)
Time frame: 12 weeks after the last PDT, up to 24 weeks after the first treatment
Overall Cosmetic Outcome of the Treated Skin 12 Weeks After Last Photodynamic Therapy (PDT) Compared to Baseline
Time frame: 12 weeks after the last PDT, up to 24 weeks after first treatment
Local Skin Reactions During First Photodynamic Therapy (PDT-1)
Time frame: during PDT treatment [3 h - 4 h ]
Local Skin Reactions During Second Photodynamic Therapy (PDT-2) for Retreated Subjects
Time frame: during PDT treatment [3 h - 4 h ]
Local Discomfort During First Photodynamic Therapy (PDT-1)
Time frame: during PDT treatment [3 h - 4 h ]
Local Discomfort During Second Photodynamic Therapy (PDT-2) for Retreated Subjects
Time frame: during PDT treatment [3 h - 4 h ]
Local Discomfort - Pain During First Photodynamic Therapy (PDT-1)
Time frame: during PDT treatment [3 h - 4 h ]
Local Discomfort - Pain During Second Photodynamic Therapy (PDT-2) for Retreated Subjects
Time frame: during PDT treatment [3 h - 4 h ]
Adverse Reactions
Time frame: up to 12 weeks after the last PDT, up to 24 weeks after first treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21910711Dirschka T, Radny P, Dominicus R, Mensing H, Bruning H, Jenne L, Karl L, Sebastian M, Oster-Schmidt C, Klovekorn W, Reinhold U, Tanner M, Grone D, Deichmann M, Simon M, Hubinger F, Hofbauer G, Krahn-Senftleben G, Borrosch F, Reich K, Berking C, Wolf P, Lehmann P, Moers-Carpi M, Honigsmann H, Wernicke-Panten K, Helwig C, Foguet M, Schmitz B, Lubbert H, Szeimies RM; AK-CT002 Study Group. 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. Br J Dermatol. 2012 Jan;166(1):137-46. doi: 10.1111/j.1365-2133.2011.10613.x. Epub 2011 Dec 21.
- Background: PubMed 23252768Dirschka T, Radny P, Dominicus R, Mensing H, Bruning H, Jenne L, Karl L, Sebastian M, Oster-Schmidt C, Klovekorn W, Reinhold U, Tanner M, Grone D, Deichmann M, Simon M, Hubinger F, Hofbauer G, Krahn-Senftleben G, Borrosch F, Reich K, Berking C, Wolf P, Lehmann P, Moers-Carpi M, Honigsmann H, Wernicke-Panten K, Hahn S, Pabst G, Voss D, Foguet M, Schmitz B, Lubbert H, Szeimies RM; AK-CT002 Study Group; AK-CT003 Study Group. 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. Br J Dermatol. 2013 Apr;168(4):825-36. doi: 10.1111/bjd.12158.
- Individual participant dataSharing planned: No
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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.
Thomas Dirschka, Prof. Dr. principal investigator
Akademische Lehrpraxis der Universität Witten-Herdecke Heinz-Fangman-Straße 57 42287 Wuppertal
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing BF-200 ALA and MAL Cream in people with Actinic Keratosis, run by Biofrontera Bioscience GmbH.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 28 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 23 Mar 2017). 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?
Percentage of Participants With Complete Response 12 Weeks After the Last Photodynamic Therapy (PDT), ITT (time frame: 12 weeks after the last PDT, up to 24 weeks after the first treatment). The study lists 3 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 NCT02799069, which also lists 2 linked publications.
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 28 Apr 2017.