E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Polymorphous Light Eruption (PMLE) |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
-To determine whether Melanotan implants given as a prophylactic can prevent or reduce the occurrence of symptoms like urticae, vesiculae, papulae, eczema, erythema and itching associated with Polymorphous Light Eruption (PMLE). |
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E.2.2 | Secondary objectives of the trial |
•To establish the safety and tolerability [defined as absence of any toxicities > Grade 3 by WHO CTC as judged from observed Adverse Events] of a sustained release implant of Melanotan delivering approximately 20 mg over a 20-25 day period in Caucasian patients with a history of recurrent polymorphous Light Eruption (PMLE). •To compare the degree of tanning at 6 anatomic sites (determined by serial reflectance) at baseline and 10, 15 and 31 days after insertion of Melanotan. •To assess immunomodulatory effects of Melanotan.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
The patients have to fulfil all of the following criteria for study participation: -Male or non-pregnant female Caucasian patients (skin types I to IV on the Fitzpatrick scale8) -Age 18 – 70 years -Weight < 90 Kg -Diagnosed PMLE-like syndrome -Written informed consent prior to the performance of any study-specific procedures
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E.4 | Principal exclusion criteria |
Any of the following criteria will exclude the patient from the study: - Personal history of melanoma, dysplastic nevus syndrome, an extraordinary number of moles or family history of melanoma in a first degree relative - Current Bowen’s disease, basal cell carcinoma, squamous cell carcinoma or other malignant skin lesions - Current pigmentary skin disorder e.g. vitiligo, melasma, haemochromatosis, mastocytosis, drug-induced pigmentation - Diagnosed with HIV/AIDS - Solarium and sunbathing, Photosensitizing medications and creams, or medications and creams that alter skin pigmentation. Examples include tetracycline antibiotics, amiodarone, chlorpromazine, hydroxychloroquine - Any evidence of clinically significant organ dysfunction, or any clinically significant deviation from normal in the clinical or laboratory determinations - No acute history of drug or alcohol abuse (at least 1 year) - History of disorders of the gastrointestinal, hepatic, renal, cardiovascular, respiratory, endocrine (incl. Diabetes), neurological (incl. Seizures), haematological (especially anaemia) or systemic disease judged to be clinically significant - Major medical or psychiatric illness -Patient not suitable (e.g., noncompliance history) for the study in the opinion of the investigator -Female who is pregnant (confirmed by positive serum β-HCG pregnancy test prior to baseline) or lactating -Females of child-bearing potential (pre-menopausal, not surgically sterile) not using adequate contraceptive measures (i.e. oral contraceptives, diaphragm plus spermicide, intrauterine device) -Participation in a clinical trial for an investigational agent within 30 days prior to the screening visit
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Endpoints:
Primary Endpoint -Incidence and severity of diagnosed outbreak of PMLE as determined by observation.
Secondary Endpoints -Change in tanning from baseline (Day 17) to day 48 across 6 anatomic sites (forehead, left cheek, right inside upper arm, left medial forearm, right side of abdomen (avoiding implant insertion site), left side of sacral region/buttock) determined by skin luminance (L*) from skin reflectance (CIELAB standard observer response) -Change in tanning from baseline to day 48 across 6 anatomic sites (forehead, left cheek, right inside upper arm, left medial forearm, right side of abdomen (avoiding implant insertion site), left side of sacral region/buttock) determined by blue/yellow colour hue (b*-value) from skin reflectance measurements (CIELAB standard observer response) -Change in melanin density (MD) from baseline to day 48 across 6 anatomic sites (forehead, left cheek, right inside upper arm, left medial forearm, right side of abdomen (avoiding implant insertion site), left side of sacral region/buttock) determined by skin reflectance measurements (MD = 100 x (0.035307 + 0.009974(R420 – R400)), Dwyer et al10) -Change in erythema from Day -6 to day 33 on the sacral region/buttock determined by UV threshold testing -Change in tanning from Screening (Day –7) to day 32 on the sacral region/buttock determined by measurement of Immediate Pigment Darkening (IPD) -Change in in-vivo inflammatory activity from baseline to day 33 (optional additional sample at day 48) as measured by C-reactive protein determination in serum -Change in frequency of regulatory T-cells from baseline to day 33 (optional additional sample at day 48) as measured by FACS analysis of CD4+ /CD25+ T cells in PBMC. -Change in in-vitro immune cell function from baseline to day 33 (optional additional sample at day 48) as measured by in vitro LPS-stimulation of monocytes in ex vivo-derived PBMCs and in vitro anti-CD3/anti-CD28 stimulation of T cells in ex vivo-derived PBMCs.
Safety Endpoints:
-Incidence of any toxicities > Grade 3 as determined by WHO-CTC (as judged from observed Adverse Events) -Type and incidence of treatment-emergent adverse events -Physical examination changes from Screening (Day –7) to Day 48 (end-of-study) -Changes in blood pressure and heart rate -Changes in clinical chemistry, haematology and urinalysis parameters.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last patient, last visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |