Erythropoietic ProtoporphyriaPhase 3NCT00979745
Phase III Confirmatory Study in Erythropoietic Protoporphyria (EPP)
A Phase 3 study testing Afamelanotide in people with Erythropoietic Protoporphyria, run by Clinuvel Pharmaceuticals Limited at 8 sites in 6 countries.
Trial summary
Afamelanotide is a man-made drug being studied for use as a preventative medication for EPP sufferers. It is a synthetically produced analogue of human alpha melanocyte stimulating hormone (alpha-MSH) and is not yet available on the market. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Erythropoietic Protoporphyria
- What is being tested?
- Afamelanotide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 8 sitesin 6 countries
- Study dates
- Sep 2009to May 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects with a diagnosis of EPP (confirmed by elevated free protoporphyrin in peripheral erythrocytes) of sufficient severity that they have requested treatment to alleviate their symptoms.
- Aged 18 - 70 years (inclusive)
- Written informed consent prior to the performance of any study-specific procedures.
Who cannot join
- Any allergy to afamelanotide or the polymer contained in the implant or to lignocaine or other local anaesthetic to be used during the administration of study medication.
- EPP patients with significant hepatic involvement.
- Personal history of melanoma or dysplastic nevus syndrome.
- Current Bowen's disease, basal cell carcinoma, squamous cell carcinoma, or other malignant or premalignant skin lesions.
- Any other photodermatosis such as PLE, DLE or solar urticaria.
- Any evidence of clinically significant organ dysfunction or any clinically significant deviation from normal in the clinical or laboratory determinations.
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- Acute history of drug or alcohol abuse (in the last 12 months).
- Patient assessed as not suitable for the study in the opinion of the Investigator (e.g. noncompliance history, allergic to local anaesthetics, faints when given injections or giving blood).
- 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).
- Sexually active men with partners of child bearing potential not using barrier contraception during the trial and for a period of three months thereafter.
- Participation in a clinical trial of an investigational agent within 30 days prior to the screening visit.
- Prior and concomitant therapy with medications which may interfere with the objectives of the study, including drugs that cause photosensitivity or skin pigmentation.
Trial locations and contacts
8 sites in 6 countries.
8 sites in 6 countries
Netherlands2 sites
Academisch Ziekenhuis Maastricht
Maastricht
Erasmus Medical Center
Rotterdam
United Kingdom2 sites
Photobiology Unit - Hope Hospital, University of Manchester
Manchester, M6 8HD
St Woolos Hospital
Newport, Wales
Finland1 site
HUS:n Iho-ja allergiasairaala (Skin and Allergy Hospital)
Helsinki
France1 site
Centre Français des Porphyries, Hôpital Louis Mourier
Colombes, Cedex, 92701
Germany1 site
Department of Dermatology , Heinrich-Heine-University Duesseldorf
Düsseldorf, 40225
About this study
Official title: A Phase III, Multicentre, Double-Blind, Randomised, Placebo-Controlled Study to Confirm the Safety and Efficacy of Subcutaneous Bioresorbable Afamelanotide Implants in Patients With Erythropoietic Protoporphyria (EPP)
Afamelanotide is a man-made drug being studied for use as a preventative medication for EPP sufferers. It is a synthetically produced analogue of human alpha melanocyte stimulating hormone (alpha-MSH) and is not yet available on the market.
The purpose of this study is to look at whether afamelanotide can reduce the number and severity of EPP symptoms when patients are exposed to light. This study will also look at how the drug is tolerated when taken by people with EPP.
Read more
The study will involve the use of an implant, which comes in the form of a small rod (approximately 2 cm x 0.15 cm) to be administered under the skin. The implant may contain the study drug afamelanotide or a placebo (inactive medication).
Over 450 subjects have been treated with afamelanotide to date with no serious safety concerns identified. For this study, afamelanotide has been formulated as a controlled release depot injection (implant). This means that the afamelanotide will be released slowly into the body over a few days. Once inserted, the implant will remain in the body after afamelanotide has been released and will slowly dissolve.
This study will help to provide more information about afamelanotide. This information will be used to determine the safety and efficacy (the ability of the drug to produce an effect) of this drug in EPP sufferers.
Up to 70 people will participate in this study from study sites across Europe.
Read the detailed description
PURPOSE:
To determine whether afamelanotide can reduce the severity of phototoxic reactions in patients with EPP.
THEORETICAL FRAMEWORK:
EPP is a genetic photosensitivity disorder where the mainstays of management are covering up from sunlight, systemic beta carotene and the use of controlled courses of UVR treatment. One of the mechanisms for the protective effects of UVR treatment is the increase in melanin content of the skin. UVR treatment causes DNA damage to skin cells and increases the risk for skin cancers, hence it is unwise for this to be used on a recurring basis. Afamelanotide, through its ability to stimulate melanin production without causing the DNA damage associated with UVR treatment, appears to be a promising agent to combat this distressing disorder.
STUDY DESIGN:
This is a phase III, randomised, placebo controlled study to evaluate the safety and efficacy of subcutaneous implants of afamelanotide in patients suffering from EPP. The study will be performed in compliance with Good Clinical Practice (GCP) including the archiving of essential documents.
METHODOLOGY:
The target population consists of male and female participants. Up to 70 patients with diagnosed EPP (from past case history) and fulfilling the necessary inclusion/exclusion criteria will be enrolled. Potential study patients will be identified from each centre's records of patients with well characterised history (or documented diagnosis) of EPP.
Patients will be enrolled and will receive afamelanotide (16 mg implants) or placebo according to the following dosing regime:
- Group A will be administered active implants on Days 0, 60, 120, 180 and 240.
- Group B will be administered placebo implants on Days 0, 60, 120, 180 and 240.
- Conditions
- Erythropoietic Protoporphyria
- Being tested
- Afamelanotide, Placebo
- Keywords
- Erythropoietic Protoporphyria, EPP, Afamelanotide
- Medical subject headings
- Protoporphyria, Erythropoietic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AfamelanotideDrug
Also called CUV1647
One 16mg subcutaneous implant every 2 months for 9 months.
PlaceboDrug
One 16mg subcutaneous implant every 2 months for 9 months.
| Study group | Role | What they receive |
|---|---|---|
| Afamelanotide | Experimental | Not described Receives: Drug: Afamelanotide |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Duration of Direct Sunlight Exposure Between 10:00 and 15:00 Hours on Days When Patients Did Not Report Phototoxicity-related Pain (Likert Pain Scale Score of 0)
Measured: From baseline to Day 270
Secondary outcomes (4)
Number of Phototoxic Reactions
Measured: 9 months
Quality of Life Measured by Patient Completed Questionnaire
Measured: 9 months
Free Protoporphyrin IX Level
Measured: 9 months
Treatment Emergent Adverse Events
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2009 (estimated)
- Study startSep 2009
- Primary completionMay 2011
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Erythropoietic ProtoporphyriaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clinuvel Pharmaceuticals Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alex Anstey, MBBS, FRCP, Principal investigator, St Woolos Hospital, NewportJorge Frank, MD, PhD, Principal investigator, Academisch Ziekenhuis MaastrichtRaili Kauppinen, MD, PhD, Principal investigator, University Central Hospital of HelsinkiEric JG Sijbrands, MD, PhD, Principal investigator, Erasmus Medical CenterJean-Charles Deybach, MD. PhD, Principal investigator, Centre Francais des Porphyries, Hopital Louis Mourier, Colombes, FranceSandra Hanneken, MD, Principal investigator, Heinrich-Heine Universität, Düsseldorf, GermanyGillian M Murphy, MD PhD, Principal investigator, Beaumont Hospital, Dublin, IrelandLesley E Rhodes, MD PhD, Principal investigator, Hope Hospital, University of Manchester, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00979745
- Sponsor's protocol ID
- CUV029
- Status last verified
- Sep 2021
- First submitted
- 17 Sep 2009
- Last updated
- 12 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Langendonk JG, Balwani M, Anderson KE, Bonkovsky HL, Anstey AV, Bissell DM, Bloomer J, Edwards C, Neumann NJ, Parker C, Phillips JD, Lim HW, Hamzavi I, Deybach JC, Kauppinen R, Rhodes LE, Frank J, Murphy GM, Karstens FPJ, Sijbrands EJG, de Rooij FWM, Lebwohl M, Naik H, Goding CR, Wilson JHP, Desnick RJ. Afamelanotide for Erythropoietic Protoporphyria. N Engl J Med. 2015 Jul 2;373(1):48-59. doi: 10.1056/NEJMoa1411481.
PubMed 26132941
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Multicentre, Double-Blind, Randomised, Placebo-Controlled Study to Confirm the Safety and Efficacy of Subcutaneous Bioresorbable Afamelanotide Implants in Patients With Erythropoietic Protoporphyria (EPP)
- ClinicalTrials.gov ID
- NCT00979745
- Acronym / sponsor ID
- CUV029
- Conditions
- Erythropoietic Protoporphyria
- Keywords
- Erythropoietic Protoporphyria, EPP, Afamelanotide
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Clinuvel Pharmaceuticals LimitedIndustry (pharma, biotech, devices)
- Study start
- Sep 2009
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 18 Sep 2009 (estimated)
- Results
- Posted 12 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Afamelanotide is a man-made drug being studied for use as a preventative medication for EPP sufferers. It is a synthetically produced analogue of human alpha melanocyte stimulating hormone (alpha-MSH) and is not yet available on the market.
The purpose of this study is to look at whether afamelanotide can reduce the number and severity of EPP symptoms when patients are exposed to light. This study will also look at how the drug is tolerated when taken by people with EPP.
The study will involve the use of an implant, which comes in the form of a small rod (approximately 2 cm x 0.15 cm) to be administered under the skin. The implant may contain the study drug afamelanotide or a placebo (inactive medication).
Over 450 subjects have been treated with afamelanotide to date with no serious safety concerns identified. For this study, afamelanotide has been formulated as a controlled release depot injection (implant). This means that the afamelanotide will be released slowly into the body over a few days. Once inserted, the implant will remain in the body after afamelanotide has been released and will slowly dissolve.
This study will help to provide more information about afamelanotide. This information will be used to determine the safety and efficacy (the ability of the drug to produce an effect) of this drug in EPP sufferers.
Up to 70 people will participate in this study from study sites across Europe.
Detailed description
PURPOSE:
To determine whether afamelanotide can reduce the severity of phototoxic reactions in patients with EPP.
THEORETICAL FRAMEWORK:
EPP is a genetic photosensitivity disorder where the mainstays of management are covering up from sunlight, systemic beta carotene and the use of controlled courses of UVR treatment. One of the mechanisms for the protective effects of UVR treatment is the increase in melanin content of the skin. UVR treatment causes DNA damage to skin cells and increases the risk for skin cancers, hence it is unwise for this to be used on a recurring basis. Afamelanotide, through its ability to stimulate melanin production without causing the DNA damage associated with UVR treatment, appears to be a promising agent to combat this distressing disorder.
STUDY DESIGN:
This is a phase III, randomised, placebo controlled study to evaluate the safety and efficacy of subcutaneous implants of afamelanotide in patients suffering from EPP. The study will be performed in compliance with Good Clinical Practice (GCP) including the archiving of essential documents.
METHODOLOGY:
The target population consists of male and female participants. Up to 70 patients with diagnosed EPP (from past case history) and fulfilling the necessary inclusion/exclusion criteria will be enrolled. Potential study patients will be identified from each centre's records of patients with well characterised history (or documented diagnosis) of EPP.
Patients will be enrolled and will receive afamelanotide (16 mg implants) or placebo according to the following dosing regime:
- Group A will be administered active implants on Days 0, 60, 120, 180 and 240.
- Group B will be administered placebo implants on Days 0, 60, 120, 180 and 240.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Afamelanotide | Experimental | Drug: Afamelanotide |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male or female subjects with a diagnosis of EPP (confirmed by elevated free protoporphyrin in peripheral erythrocytes) of sufficient severity that they have requested treatment to alleviate their symptoms.
- Aged 18 - 70 years (inclusive)
- Written informed consent prior to the performance of any study-specific procedures.
Key exclusion criteria (13 listed)
- Any allergy to afamelanotide or the polymer contained in the implant or to lignocaine or other local anaesthetic to be used during the administration of study medication.
- EPP patients with significant hepatic involvement.
- Personal history of melanoma or dysplastic nevus syndrome.
- Current Bowen's disease, basal cell carcinoma, squamous cell carcinoma, or other malignant or premalignant skin lesions.
- Any other photodermatosis such as PLE, DLE or solar urticaria.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AfamelanotideAlso: CUV1647One 16mg subcutaneous implant every 2 months for 9 months. | Drug | Afamelanotide |
| PlaceboOne 16mg subcutaneous implant every 2 months for 9 months. | Drug | Placebo |
Primary outcome
The Duration of Direct Sunlight Exposure Between 10:00 and 15:00 Hours on Days When Patients Did Not Report Phototoxicity-related Pain (Likert Pain Scale Score of 0)
Time frame: From baseline to Day 270
4 secondary outcomes
Number of Phototoxic Reactions
Time frame: 9 months
Quality of Life Measured by Patient Completed Questionnaire
Time frame: 9 months
Free Protoporphyrin IX Level
Time frame: 9 months
Treatment Emergent Adverse Events
Time frame: 9 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26132941Langendonk JG, Balwani M, Anderson KE, Bonkovsky HL, Anstey AV, Bissell DM, Bloomer J, Edwards C, Neumann NJ, Parker C, Phillips JD, Lim HW, Hamzavi I, Deybach JC, Kauppinen R, Rhodes LE, Frank J, Murphy GM, Karstens FPJ, Sijbrands EJG, de Rooij FWM, Lebwohl M, Naik H, Goding CR, Wilson JHP, Desnick RJ. Afamelanotide for Erythropoietic Protoporphyria. N Engl J Med. 2015 Jul 2;373(1):48-59. doi: 10.1056/NEJMoa1411481.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alex Anstey, MBBS, FRCP principal investigator
St Woolos Hospital, Newport
Jorge Frank, MD, PhD principal investigator
Academisch Ziekenhuis Maastricht
Raili Kauppinen, MD, PhD principal investigator
University Central Hospital of Helsinki
8 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Afamelanotide in people with Erythropoietic Protoporphyria, run by Clinuvel Pharmaceuticals Limited at 8 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Netherlands, United Kingdom, Finland, France, Germany and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Duration of Direct Sunlight Exposure Between 10:00 and 15:00 Hours on Days When Patients Did Not Report Phototoxicity-related Pain (Likert Pain Scale Score of 0) (time frame: From baseline to Day 270). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00979745, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2021; AzTrials last refreshed its copy on 30 Oct 2026.