Evaluation of Efficacy and Safety of BF-200 ALA Used With Photodynamic Therapy in Patients With Actinic Keratosis.
Condition: Actinic Keratosis
MeSH terms: Keratosis, Actinic; Keratosis
Intervention: Vehicle; BF-200 ALA
Intervention description: topical treatment for photodynamic therapy combining vehicle application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).; topical treatment for photodynamic therapy combining drug application and subsequent illumination with broad or narrow spectrum light sources (after 3 h of drug incubation).
Intervention MeSH terms: Aminolevulinic Acid
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Enrollment: 122.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      The aim of the study was to evaluate the efficacy and safety of BF-200 ALA (Ameluz) used with
      photodynamic therapy (PDT) in patients suffering from actinic keratosis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects were willing and able to sign informed consent form.

          -  Men and women aged between 18 and 85 years inclusive.

          -  Subjects had a general good and stable health condition as confirmed by a physical
             examination and by medical history.

          -  Subjects with clinically stable medical conditions including, but not limited to the
             following diseases were allowed to be included into the study, if the medication taken
             for the treatment of the disease did not match the criteria of the excluded or
             disallowed medications listed in points 7, 10, 11 and 12 of the exclusion criteria:

               -  controlled hypertension

               -  diabetes mellitus type II

               -  hypercholesterolemia

               -  osteoarthritis

          -  Subjects accepted to abstain from sunbathing and the solarium during the study.

          -  Subjects had at least 4 but not more than 8 clinically confirmed actinic keratosis
             (AK) target lesions of mild to moderate intensity within the face or bald scalp
             (excluding eyelids, lips and mucosa), i.e. AK grade I and II according to Olsen et.
             al. 1991.

          -  To document and confirm the diagnosis of the investigators:

               -  Photodocumentation of a representative lesion had to be evaluated and confirmed
                  by an independent expert.

               -  A pre-study biopsy had to be taken from a second representative AK lesion and was
                  histopathologically evaluated by a dermato-pathological expert.

          -  If the evaluation of the photo by the independent reviewer could not confirm the
             diagnosis of the investigator, then the biopsy result decided whether the subject was
             eligible for the study.

          -  The AK lesions had to be discrete and quantifiable; the distance from one lesion to
             its neighbor lesion was greater than 1.0 cm

          -  The diameter of each AK lesion was not less than 0.5 cm and not greater than 1.5 cm.
             The size of each baseline AK lesion was recorded by measuring the two largest
             perpendicular diameters. To describe irregular lesions (ellipsoidal) investigators
             measured the major and minor axis. Both axes had to be above the minimum of 0.5 cm and
             less than 1.5 cm.

          -  The subjects were free of any significant physical abnormalities (e.g., tattoos,
             dermatoses) in the potential treatment area that might cause difficulty with
             examination or final evaluation.

          -  The subjects were willing to stop using moisturizers and any other topical treatments
             with anti-aging products, vitamin A, vitamin C, and/or vitamin E containing ointments
             and creams, and green tea preparations during the study within the treatment area.
             Sunscreens were allowed, but were not to be applied in the treatment area within
             approximately 24 hours before a clinical visit with lesion count.

          -  Women of childbearing potential were only allowed to participate in this study, if
             they used a highly effective method of contraception and had a negative serum
             pregnancy test.

        Exclusion Criteria:

          -  Had known hypersensitivity to 5-aminolevulinic acid (ALA).

          -  Were subjects under immunosuppressive therapy.

          -  Suffered from porphyria.

          -  Showed hypersensitivity to porphyrins.

          -  Suffered from photodermatoses.

          -  Had inherited or acquired coagulation defects.

          -  Had received medication with hypericin or systemically acting drugs with phototoxic or
             photoallergic potential such as psoralens, tetracyclines, nalidixic acid, furosemide,
             amiodarone, phenothiazines, quinolones, fibrates, or phytotherapy with St. John's
             wort, arnica, or valerian or topically applied phototoxic substances like tar, pitch,
             psoralens or some dyes like thiazide, methylene blue, toluidine blue, eosine, Bengal
             rose, acridine within 8 weeks prior to treatment with study drug and photodynamic
             therapy (PDT).

          -  Had evidence of clinically significant, unstable medical conditions such as

               -  metastatic tumor or tumor with high probability of metastatic spread

               -  cardiovascular (NYHA class III, IV)

               -  immunosuppressive

               -  hematological, hepatic, renal, neurological, endocrine

               -  collagen-vascular

               -  gastrointestinal

          -  Had currently other malignant or benign tumors of the skin within the treatment area
             (e.g., malignant melanoma, basal cell carcinoma, invasive squamous cell carcinoma).

          -  Used any topical treatment in the treatment area within 12 weeks before PDT treatment
             with BF-200 ALA; biopsy taken at the screening visit was allowed.

          -  Used topical treatment with ALA or MAL (methyl-aminolevulinic acid hydrochloride)
             outside the treatment area during participation in the study.

          -  Systemic treatments of one of the following within the designated period before

        PDT with BF-200 ALA:

          -  Interferon - 6 weeks

          -  Immunomodulators or immunosuppressive therapies - 10 weeks

          -  Cytotoxic drugs - 6 months

          -  Investigational drugs - 8 weeks

          -  Drugs known to have major organ toxicity - 8 weeks

          -  Corticosteroids (oral or injectable) - 6 weeks

          -  Inhaled corticosteroids (>1200 µg/day for beclomethasone, or >600 µg/day for
             fluticasone) - 4 weeks

          -  Methyl-aminolevulinic acid hydrochloride or ALA - 12 weeks

          -  Known allergy against polysorbate 80, caprylic/capric acid triglycerides, isopropyl
             alcohol, disodium phosphate dihydrate, sodium hydroxide, hydrochloric acid, propylene
             glycol; sodium benzoate.

          -  Were known to be pregnant or lactating (currently or within the past 3 months).

          -  Had any dermatological disease in the treatment area or surrounding area that could be
             exacerbated by treatment with topical ALA or caused difficulty with examination (e.g.
             psoriasis, eczema).

          -  Showed cornu cutaneum like alterations of the skin in the face or on the bald scalp
             (target area).

          -  Were currently or within the past 8 weeks participating in another clinical study.

          -  Had active chemical dependency or alcoholism as assessed by the investigator.

          -  Confirmed diagnosis of HIV.