Title

Safety and Efficacy Study for the Treatment of Non-Aggressive Basal Cell Carcinoma With Photodynamic Therapy
A Randomized, Observer Blind, Multinational Phase III Study to Evaluate the Safety and Efficacy of BF-200 ALA (Ameluz®) in Comparison to Metvix® in the Treatment of Non-aggressive Basal Cell Carcinoma (BCC) With Photodynamic Therapy (PDT)
  • Phase

    Phase 3
  • Study Type

    Interventional
  • Study Participants

    281
The aim of this study is to test the effectiveness and safety of the medicine Ameluz® (5-aminolevulinic acid) in comparison to methyl-aminolevulinate (MAL), used with photodynamic therapy (PDT), to treat thin, non-aggressive BCC (basal cell carcinoma).
The treatment comprises of up to 2 PDT cycles, each with two PDT sessions one week apart.

If 12 weeks after the the second PDT all lesions are completely cleared the patient will enter the follow-up phase. In case of remaining lesions the patient will receive a second PDT cycle starting on the same day.
Study Started
Jan 28
2014
Primary Completion
Nov 17
2015
Study Completion
Sep 09
2020
Results Posted
Mar 11
2019
Last Update
Nov 03
2022
Estimate

Drug BF-200 ALA

Topical treatment for photodynamic therapy combining drug application and subsequent illumination with a narrow spectrum light source (after 3 h of drug incubation)

  • Other names: Ameluz

Drug methyl-aminolevulinate

Topical treatment for photodynamic therapy combining drug application and subsequent illumination with a narrow spectrum light source (after 3 h of drug incubation)

  • Other names: Metvix / Metvixia

BF-200 ALA Active Comparator

Topical application of BF-200 ALA gel containing 78 mg/g 5-aminolevulinic acid. Application of a 1 mm thick layer covering each lesion and 0.5 to 1 cm of surrounding margin.

methyl-aminolevulinate Active Comparator

Topical application of Metvix creme containing 160 mg/g methyl-aminolevulinate. Application of a 1 mm thick layer covering each lesion and 0.5 to 1 cm of surrounding margin.

Criteria

Main Inclusion Criteria:

Willing and able to sign informed consent form; obtained in writing before starting any study procedures
Presence of 1-3 thin (≤2 mm thickness), clinically non-aggressive, primary BCC lesions (primary superficial, nodular, or mixed superficial/nodular) in the face/forehead, bald scalp, extremities and/or neck/trunk. Confirmation of non-aggressiveness and thickness of BCC through biopsies taken at screening for at least one lesion. Lesions non-eligible according to biopsy should timely be removed by surgery or cryotherapy
Diameters of lesions should range between ≥0.5cm and ≤2cm; total maximal treated area is 10cm² (including 0.5-1.0cm margin surrounding each lesion)
Target BCC lesions must be discrete and quantifiable and have to be located within 1-2 treatment areas
Free of significant physical abnormalities (eg tattoos, dermatoses) in potential treatment area that may cause difficulty with examination or final evaluation
Accept to abstain from extensive sunbathing and use of solarium during observer blind part. Patients with sunburn within treatment areas cannot be included until fully recovered
Healthy patients and patients with clinically stable medical conditions, including, but not limited to controlled hypertension, diabetes mellitus type II, hypercholesterolemia, and osteoarthritis, will be permitted to be included in study if their medication is not prohibited by protocol
Women of childbearing potential are permitted to participate in study only if they have a negative serum pregnancy test at screening and willingness to use a highly effective method of contraception during observer blind part

Main Exclusion Criteria:

History of hypersensitivity to 5-ALA or any ingredient of BF-200 ALA, MAL or any ingredient of Metvix®, including arachis oil, or to peanut or soya
Hypersensitivity to porphyrins
Current treatment with immunosuppression therapy
Presence of porphyria
Presence of BCC lesions on embryonic fusion planes (H-zone)
Presence of more than 3 BCCs
Presence of malignant or benign tumors of the skin other than non-aggressive BCC within the treatment area (eg malignant melanoma, squamous cell carcinoma (SCC), aggressive BCC clinically diagnosed at screening) within the last 12 weeks
Gorlin Syndrome or Xeroderma pigmentosum
Presence of photodermatoses
Treatment of lesions (actinic keratosis (AK), BCC, SCC, Bowens disease, melanoma) ≤12 weeks prior to first PDT, except physical treatments (eg cryosurgery, excision surgery) that will not be allowed ≤6 weeks prior to first PDT (Visit 2). Lesion(s) that seemed eligible clinically which could not be confirmed by biopsy, and which are located ≥10cm to an eligible lesion should timely be removed physically only
Presence of inherited or acquired coagulation defect
Start of intake of medication with hypericin or systemically-acting drugs with phototoxic or photoallergic potential within 8 weeks prior to screening
Clinically relevant cardiovascular, hepatic, renal, neurologic, endocrine, or other major systemic disease making implementation of protocol or interpretation of study results difficult

Evidence of clinically significant (CS), unstable medical conditions, eg:

Metastatic tumor or tumor with high probability of metastasis
Cardiovascular disease (New York Heart Association [NYHA] class III, IV)
Immunosuppressive condition
Hematologic, hepatic, renal, neurologic, or endocrine condition
Collagen-vascular condition
Gastrointestinal condition
Topical treatment with 5-ALA or MAL outside treatment area during the observer blind part
Any topical treatment including diclofenac and immunomodulatory agents (eg imiquimod, ingenol mebutate) 12 weeks prior to first PDT session and during observer blind part
Any physical treatment during the observer blind part within treated target areas with exception of lesion(s) determined non-eligible by biopsy

Summary

BF-200 ALA

Methyl-aminolevulinate

All Events

Event Type Organ System Event Term BF-200 ALA Methyl-aminolevulinate

Overall Patient Complete Response Rate Assessed 12 Weeks After the Last PDT

Overall patient complete response rate assessed 12 weeks after the last PDT. The indicated values give the percentage of overall complete responders. An overall complete responder is defined as a patient in whom all treated lesions were cleared. The PP set is the primary analysis set for the analyses of the primary endpoint.

BF-200 ALA

93.4
Percentage of Patients
95% Confidence Interval: 87.0 to 96.9

Methyl-aminolevulinate

91.8
Percentage of Patients
95% Confidence Interval: 84.6 to 96.0

Lesion Complete Response Assessed 12 Weeks After the Last PDT

Lesion complete response (completely cleared individual lesions) assessed 12 weeks after the last PDT. The indicated values give percentage of overall completely cleared individual lesions. The PP set is the primary analysis set for the analysis of the secondary endpoint.

BF-200 ALA

94.6
Percentage of Individual Lesions
95% Confidence Interval: 89.3 to 97.5

BF-200 ALA

94.6
Percentage of Individual Lesions
95% Confidence Interval: 89.3 to 97.5

Methyl-aminolevulinate

92.9
Percentage of Individual Lesions
95% Confidence Interval: 86.6 to 96.5

Methyl-aminolevulinate

92.9
Percentage of Individual Lesions
95% Confidence Interval: 86.6 to 96.5

Reduction of Lesion Area 12 Weeks After the Last PDT Compared to Baseline

Reduction of total lesion area (summation of sizes of all treated lesions) per patient, assessed 12 weeks after the last PDT. The PP set is the primary analysis set for the analysis of the secondary endpoint. Please note that the high SD for BF-200 ALA is due to a patient who had increased lesion area fom 63 mm² at baseline to 225 mm² 12 weeks after PDT. This lesion area included a lesion that was later confirmed to be benign skin condition (lentigo solaris).

BF-200 ALA

-94.5
Percentage of Change (Mean)
Standard Deviation: 35.07

Methyl-aminolevulinate

-97.0
Percentage of Change (Mean)
Standard Deviation: 13.37

Patient Complete Response 12 Weeks After PDT-2

Patient complete response (complete clearance of all treated lesions) assessed 12 weeks after PDT-2 (first PDT cycle). The PP set is the primary analysis set for the analysis of the secondary endpoint.

BF-200 ALA

57.9
Percentage of Patients
95% Confidence Interval: 48.5 to 66.7

Methyl-aminolevulinate

56.4
Percentage of Patients
95% Confidence Interval: 46.6 to 65.7

Cosmetic Outcome 12 Weeks After Last PDT (Including Patients With a Sum Score of 0 at Baseline)

Overall cosmetic outcome 12 weeks after last PDT is calculated as difference between 12 weeks after PDT sum score and baseline sum score of all skin quality assessments. Each of the below skin quality characteristics are assessed on a 4-point scale from 0 (none) to 3 (severe) by the investigator at baseline and 12 weeks after last PDT: Skin surface Hyperpigmentation Hypopigmentation Mottled or irregular pigmentation Degree of scarring Atrophy Cosmetic outcome categories are: Very good: 12 weeks sum score improved by at least 2 points compared to baseline Good: 12 weeks sum score improved by 1 point compared to baseline Satisfactory: 12 weeks sum score identical to the one at baseline Unsatisfactory: 12 weeks sum score worsened by 1 point compared to baseline Impaired: 12 weeks sum score worsened by at least 2 points compared to baseline

BF-200 ALA

Good

11.7
Percentage of Patients
95% Confidence Interval: 6.8 to 19.1

Impaired

15.0
Percentage of Patients
95% Confidence Interval: 9.4 to 22.9

Satisfactory

35.8
Percentage of Patients
95% Confidence Interval: 27.4 to 45.2

Unsatisfactory

14.2
Percentage of Patients
95% Confidence Interval: 8.7 to 22.0

Very good

23.3
Percentage of Patients
95% Confidence Interval: 16.3 to 32.1

Methyl-aminolevulinate

Good

18.3
Percentage of Patients
95% Confidence Interval: 11.8 to 27.2

Impaired

17.4
Percentage of Patients
95% Confidence Interval: 11.1 to 26.1

Satisfactory

29.4
Percentage of Patients
95% Confidence Interval: 21.2 to 39.0

Unsatisfactory

20.2
Percentage of Patients
95% Confidence Interval: 13.3 to 29.2

Very good

14.7
Percentage of Patients
95% Confidence Interval: 8.9 to 23.0

Cosmetic Outcome 12 Weeks After the Last PDT (Including Patients With a Baseline Sum Score >1)

Overall cosmetic outcome 12 weeks after last PDT is calculated as difference between 12 weeks after PDT sum score and baseline sum score of all skin quality assessments. Each of the below skin quality characteristics are assessed on a 4-point scale from 0 (none) to 3 (severe) by the investigator at baseline and 12 weeks after last PDT: Skin surface Hyperpigmentation Hypopigmentation Mottled or irregular pigmentation Degree of scarring Atrophy Cosmetic outcome categories are: Very good: 12 weeks sum score improved by at least 2 points compared to baseline Good: 12 weeks sum score improved by 1 point compared to baseline Satisfactory: 12 weeks sum score identical to the one at baseline Unsatisfactory: 12 weeks sum score worsened by 1 point compared to baseline Impaired: 12 weeks sum score worsened by at least 2 points compared to baseline

BF-200 ALA

Good

20.0
Percentage of Patients
95% Confidence Interval: 11.7 to 31.6

Impaired

5.7
Percentage of Patients
95% Confidence Interval: 1.8 to 14.7

Satisfactory

22.9
Percentage of Patients
95% Confidence Interval: 14.0 to 34.7

Unsatisfactory

11.4
Percentage of Patients
95% Confidence Interval: 5.4 to 21.8

Very good

40.0
Percentage of Patients
95% Confidence Interval: 28.7 to 52.4

Methyl-aminolevulinate

Good

27.0
Percentage of Patients
95% Confidence Interval: 17.7 to 38.8

Impaired

6.8
Percentage of Patients
95% Confidence Interval: 2.5 to 15.7

Satisfactory

32.4
Percentage of Patients
95% Confidence Interval: 22.3 to 44.4

Unsatisfactory

12.2
Percentage of Patients
95% Confidence Interval: 6.1 to 22.3

Very good

21.6
Percentage of Patients
95% Confidence Interval: 13.2 to 33.0

Patient Recurrence Rate (Overall, Cumulative)

Patient recurrence rate defined as the number of patients with at least one recurrent lesion during FU after complete clearance 12 weeks after the last PDT

BF-200 ALA

16.9
percentage of patients (cumulative)

Methyl-aminolevulinate

15.5
percentage of patients (cumulative)

Lesion Recurrence Rate (Cumulative)

Lesion recurrence rate defined as the number of completely cleared lesions 12 weeks after the last PDT showing recurrence during FU. Overall and subgroup analysis (nodular basal cell carcinoma (nBCC) and superficial basal cell carcinoma (sBCC)).

BF-200 ALA

nBCC

25.0
percentage of lesions (cumulative)

Overall

13.5
percentage of lesions (cumulative)

sBCC

10.3
percentage of lesions (cumulative)

BF-200 ALA

nBCC

25.0
percentage of lesions (cumulative)

Overall

13.5
percentage of lesions (cumulative)

sBCC

10.3
percentage of lesions (cumulative)

Methyl-aminolevulinate

nBCC

21.4
percentage of lesions (cumulative)

Overall

13.4
percentage of lesions (cumulative)

sBCC

11.9
percentage of lesions (cumulative)

Methyl-aminolevulinate

nBCC

21.4
percentage of lesions (cumulative)

Overall

13.4
percentage of lesions (cumulative)

sBCC

11.9
percentage of lesions (cumulative)

Total

281
Participants

Age, Categorical

Ethnicity (NIH/OMB)

Sex: Female, Male

Overall Study

BF-200 ALA

Methyl-aminolevulinate

Drop/Withdrawal Reasons

BF-200 ALA

Methyl-aminolevulinate