Primary efficacy objective:To show the non-inferior efficacy of Metvix® Natural Day Light Photo Dynamic Therapy (NDL-PDT) versus Metvix® conventional Photo Dynamic Therapy (c-PDT) in Subjects with mild and moderate AKs at Week 12 in terms of percent…
ID
Source
Brief title
Condition
- Cutaneous neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy endpoint is the lesion complete response rate, defined as
the percentage of pre-existing and treated lesions at baseline that were
assessed as clear at Week 12.
Secondary outcome
Secondary efficacy endpoints
- Lesion complete response rate for mild lesions only.
- Subject-side complete response rate defined as the percentage of subjects
with all treated lesions clear in the corresponding TA, at Week 12.
- change in lesion severity
- number of new lesion
Primary Safety endpoint
- subject's self assessment of pain at baseline post-PDT procedures
Secondary Safety endpoint
- Incidence and severity of Adverse Events
- skin aspect of lesion in complete response
Other endpoint: weather and light asessment
Background summary
Actinic keratoses are common cutaneous lesions. They are hyperkeratotic lesions
on skin. These cutaneous lesions are superficial. They are due to ultra-violet
radiations which damage and disturb the skin cell cycle.
Actinic keratoses are found in high number on areas typically exposed to sun
such as face, scalp, arms, neck, and hands. It is a condition of elderly
people, with fair skin, mainly men, with outdoors activites during their life.
With ageing of population and growing outdoors leazure activities, the
incidence of actinic keratosis is increasing. The reported prevalence is
between 11% et 60% depending on world region.
The actinic keratoses are not a serious condition but tey are pre-cancerous
lesions requested to be treated due to their risk of transformation into
squamous cell carcinoma (non melanoma skin cancer).
Several treatment are available on market, topical, surgical, cryotherapya nd
oral. In addition to high efficacy, the preference of patients and physicians
patient goes to treatment less painful, well tolerated, not inducing scra,
allowing to treat large area at the same time.
The photo-dynamic therapy is tretrecommended as first line treatment for
actinic keratoses. It is very efficient allowing treatment of large areas with
an excellent cosmesis. This treatment consist of the application of a topical
photosentizer then activated by a light source.
The Metvix® is a topical treatment indicated for mild and moderate actinic
keratoses. Following application, it penetrates into the skin. It has a high
selectivity for neoplasic celles where hit preferably accumulates and
transforms into Protoporphyrine IX. Under red light (lamp), a reaction leads to
transformation into free radicals causing apoptosis and necrosis of noplasic
cells.
Metvix ®photodynamic therapy is attractive but could be consider lenghtly as it
request an pplication under occlusion for 3 hours. Some patienst have reported
this treatment as painful.
Recently, some clinical studies have showed that Metvix® can be activated with
natural daylight, the protoporphyrine IX absorbing several peaks in visible
light (505, 540, 580 et 630 nanometers). The Metvix® activatad by the natural
daylight shows a similar efficacy when compared to Metvix® activated by red
light (lamp) for mild and moderate actinic keratoses. Moreover, the treatment
with natural daylight is reported as less painful for patients, protoporphyrine
IX activation being immediate right after its production versus after 3 hours
accumulation for activation by red light (lamp).
The aim of this European study multicentric is to confirmed that Metvix®
activated by natural daylight has a similar efficacy and is less painful in
comparizon to Metvix® activated by red light (lamp) in patients with mild and
moderate actinic keratoses.
Moreover to assess sensitivity of the method Metvix® activated by natural
daylight , a comparative arm Metvix® placebo activated by red light (lamp)
will be tested (ratio 1:6) in this study.
This is a randomised, controlled, intraindividual (right/left) comparative
study.
The investigator in charge of assessment will be blinded of treatment received.
A tird party, referenced as procedure operator will be in charge of treatment
and ilumination.
This is a multicentric study, including approximately 5 countries in Europe and
15 sites.
120 patients will be enrolled, above 18 years, with symetrical areas in terms
of actinic keratoses mild and moderate, on the face or on the scalp and meeting
eligibility criteria.
The patients will receive Metvix® activated by the natural daylight on right or
left face/scalp and Metvix® activated by red light on contralateral side.
Study objective
Primary efficacy objective:
To show the non-inferior efficacy of Metvix® Natural Day Light Photo Dynamic
Therapy (NDL-PDT) versus Metvix® conventional Photo Dynamic Therapy (c-PDT) in
Subjects with mild and moderate AKs at Week 12 in terms of percent reduction in
lesions count.
Primary safety objective:
To compare the Subject's self-assessment of pain of Metvix® NDL-PDT with that
of Metvix® c-PDT.
Study design
This study will be conducted as a multi-centre, randomized, investigator-blind,
active and vehicle-controlled, intra-individual study.
This study will compare Metvix* NDL-PDT to Metvix* c-PDT (Group 1).
In addition this study will include a Metvix® NDL-PDT arm versus Metvix®
vehicle cream c PDT (Placebo) to assess the sensitivity of the trial (Group 2).
Intervention
The patients will be followed during 12 weeks and will have 3 visits. They will
be treated at their first visit and will be assessed at 1 and 12 weeks by the
investigator. Subjects will also be requested to complete questionnaires.
Study burden and risks
This clinical study is performed with a product within the indication approved
on the market. Related adverse event are known and well described in the SmPC.
Basically the possible reactions are due to the toxic effects of the Metvix®
activation by the light (photodynamic therapy).
Based on the 3 studies published by Wiegell et al, and on the preliminary
results of the Galderma study RD.03.SPR.29102, the use of NDL- PDT is expected
to improve the tolerability of the treatment (less pain during illumination)
and simplify the use of Metvix® while maintaining a similar efficacy compared
to the c- PDT.
Les Templiers, 2400 Route des Colles BP 87
Biot Cedex 06410
FR
Les Templiers, 2400 Route des Colles BP 87
Biot Cedex 06410
FR
Listed location countries
Age
Inclusion criteria
- Male or female, who is at least 18 years of age or older,
- Clinical diagnosis of mild (Grade 1) and/or moderate (Grade 2) AKs on the face or the scalp on treated areas (TAs) according to Olsen et al scale (1991). (e.g.: thin and/or non-hyperkeratotic AKs),
- Subject with two symmetrical TAs (either two half scalps or two half faces excluding ears, chin, bridge of the nose, eyelids and lips inside the vermillion border): no more than a twofold difference in terms of total number of lesions between the two TAs
- TA comparable in terms of size: 6 by 16 cm at a maximum
- A minimum of 5 AKs (either mild, moderate or both) per TA
- No more than two lesions difference in number of moderate AKs between the two TAs.
- Female of non-childbearing potential, OR female of childbearing potential with a negative urine pregnancy test (UPT).
- If female of childbearing potential, they should:
- have been strictly abstinent 1 month prior to Baseline and agrees to remain abstinent for the duration of the clinical trial,
- and/or agree to use a highly effective and approved contraceptive method(s) during the duration of the clinical trial (bilateral tubal ligation OR combined oral contraceptives (oestrogens and progesterone) or implanted or injectable contraceptives with a stable dose for at least 1 month prior to Baseline OR vasectomized partner for at least 3 months prior to Baseline OR hormonal intra uterine device (IUD) inserted at least 1 month prior to Baseline.
Exclusion criteria
- Subject with clinical diagnosis of at least one severe (Grade 3) AK on TAs according to Olsen et al (1991) scale (e.g. hyperkeratotic AKs),
- Subject with pigmented AK on the TAs,
- Immuno-compromised Subject for idiopathic, disease specific or therapeutic reasons;
- Subject with porphyria,
- Subject with clinical diagnosis of other skin disease (including non-melanoma skin cancer) on the TAs which, in the opinion of the investigator, might interfere with the interpretation of the clinical results,
- Subject with systemic diseases that, in the opinion of the investigator might interfere with the interpretation of the clinical results,
- History of hypersensitivity to nut products (e.g. peanut and almond oil) or soya,
- Subject with a known past history of skin cancer in the TAs
- Past history of skin melanoma
- The Subject has received, applied or taken the following treatments or Procedures within the specified time frame prior to the Baseline visit:
Topical treatment(s) on TAs:
5-Fluorouracil, diclofenac, imiquimod, retinoids, ingenol mebutat (Pep-005) : Duration 12 weeks
Surgical: elliptical excision, excision and reconstructive surgery, Mohs* micrographic surgery, chemical peels/chemosurgery, cryosurgery, dermabrasion: Duration 12 weeks
PDT: Duration 12 weeks
Laser: Duration 12 weeks
Electrocoagulation: Duration 12 weeks
Radiotherapy and UV radiation therapy: Duration 12 weeks
Investigative therapies for Actinic Keratoses: Duration 12 weeks
Alpha-hydroxy acid, salicylic acid ointment, urea: Duration 2 weeks
Systemic treatment(s)
Systemic retinoids: Duration 12 weeks
Immunosuppressive drugs (such as glucocorticoids, cytostatic, antibodies, drugs acting on immunophilins, interferon, opioids , TNF binding proteins, Mycophenolate, small biologics agents):Duration 12 weeks
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-000973-54-NL |
| CCMO | NL44221.091.13 |