E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• Evaluate the impact of afamelanotide on minimal erythema dose (MED) in patients with XP |
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E.2.2 | Secondary objectives of the trial |
• Evaluate the impact of afamelanotide on UV-induced DNA damage and repair capacity in patients with XP. • Evaluate the safety and tolerability of afamelanotide in patients with XP. • Evaluate the impact of afamelanotide on the skin disease severity of patients with XP. • Evaluate the impact of afamelanotide on the skin melanin density of patients with XP. • Evaluate the impact of afamelanotide on the quality of life of patients with XP. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female patient with a molecular-genetically confirmed diagnosis of XP-C. - Aged 18-75 years. - Providing written Informed Consent prior to the performance of any study-specific procedure. - Willing and able to comply with the conditions specified in the protocol and study procedures, in the opinion of the Investigator.
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E.4 | Principal exclusion criteria |
- Known allergy to afamelanotide or the polymer contained in the implant - Presence of severe hepatic disease or hepatic impairment. - Renal impairment. - Any other medical condition which may interfere with the study protocol. - Existing melanoma - Female who is pregnant (confirmed by positive urine β-HCG pregnancy test) 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) or a life-style excluding pregnancy, for up to three months after the last implant administration. - Sexually active man with a partner of child-bearing potential (pre-menopausal, not surgically sterile) who is not using adequate contraceptive measures, as described above. - Use of any other prior and concomitant therapy which may interfere with the objective of the study, within 30 days prior to the Screening visit. - Participation in a clinical trial for an investigational agent within 30 days prior to the Screening visit. - Not suitable for trial participation in the opinion of the Investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• The change in MED (analysis will compare the individual fold increase in MED from Day 0 to the post-treatment assessment at Day 76).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
from Day 0 to the post-treatment assessment at Day 76 |
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E.5.2 | Secondary end point(s) |
• The changes in UV-induced DNA damage and repair capacity from baseline Day 0 to Day 76 or Premature Termination Visit (if applicable), as measured through analysis of UV photoproducts and DNA repair mechanisms on irradiated skin in comparison with non-irradiated skin (refer to the biopsy protocol for details). • The change in skin disease severity from baseline Day 0 to Day 70, Day 75 or 76 or Premature Termination Visit (if applicable) and Day 238(±14) as measured by: o 5-point IGA scale; o 11-point Likert-type scale; • The change in skin disease severity from Screening/Day -1/Day 0 to Day 75 or 76 or Premature Termination Visit (if applicable) and Day 238(±14) as measured by the European XP severity score; • The change in melanin density from baseline Day -1 or 0 to Days, 14 28, 42, 56, 75 or 76 or Premature Termination Visit (if applicable) and 238(±14) as measured by spectrophotometry. • The change in Quality of Life from Screening/Day 0/Day 1 to Day 70, 75 or 76 or Premature Termination Visit (if applicable) and 238(±14), as measured by the two instruments: o WPAI:GH o XP-derived QOLEB
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 0 to Day 76 or Premature Termination Visit (if applicable); From baseline Day 0 to Day 70, Day 75 or 76 or Premature Termination Visit (if applicable) and Day 238(±14); From Screening/Day -1/Day 0 to Day 75 or 76 or Premature Termination Visit (if applicable) and Day 238(±14) |
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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 | No |
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 | No |
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 | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
E.8.7 | Trial has a data monitoring committee | No |
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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Twelve-week open label study in adult patients with confirmed XP plus six month follow up. |
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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 | |
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 months | 9 |