Erythropoietic ProtoporphyriaPhase 3NCT01605136
Phase III Confirmatory Study in Erythropoietic Protoporphyria
A Phase 3 study testing Afamelanotide in people with Erythropoietic Protoporphyria, run by Clinuvel Pharmaceuticals Limited at 7 sites in United States.
Trial summary
This is a randomized placebo-controlled study to be conducted in two parallel study arms for a six month period (three doses). Between 75 and 100 eligible patients will be enrolled. Read more about this study
- Who is it for?
- Ages 18 years and older
- 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
- 93 participants
- Where
- 7 sitesUnited States
- Study dates
- May 2012to Jul 2013
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects with characteristic symptoms of EPP phototoxicity and a biochemically-confirmed diagnosis of EPP.
- Aged 18 years old and above (inclusive).
- Able to understand and sign the written Informed Consent Form.
- Willing to take precautions to prevent pregnancy until completion of the study (Day 180).
Who cannot join
- Any allergy to afamelanotide or the polymer contained in the implant or to lidocaine or other local anesthetic to be used during the administration of the 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 polymorphic light eruption, actinic prurigo, discoid lupus erythematosus, chronic actinic dermatitis or solar urticaria.
- Any evidence of clinically significant organ dysfunction or any clinically significant deviation from normal in the clinical or laboratory determinations.
Show all 12Show fewer
- Acute history of drug or alcohol abuse (in the last 6 months).
- Patient assessed as not suitable for the study in the opinion of the Investigator (e.g. noncompliance history, allergic to local anesthetics, faints when given injections or giving blood).
- Participation in a clinical trial for 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.
- 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).
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University of Alabama
Birmingham, Alabama, 35294
Carolina's Medical Center Cannon Research
Charlotte, North Carolina, 29203
Henry Ford Medical Center
Detroit, Michigan, 48202
University of Texas
Galveston, Texas, 77555
Mt. Sinai
New York, New York, 10029
University of Utah
Salt Lake City, Utah, 84112
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: A Phase III, Multicentre, Double-Blind, Randomized, Placebo-Controlled Study to Confirm the Safety and Efficacy of Subcutaneous Bioresorbable Afamelanotide Implants in Patients With Erythropoietic Protoporphyria (EPP)
This is a randomized placebo-controlled study to be conducted in two parallel study arms for a six month period (three doses). Between 75 and 100 eligible patients will be enrolled. Patients will receive afamelanotide (16 mg implants) or placebo according to the following dosing regimen:
- Group A will be administered afamelanotide implants on Days 0, 60 and 120
- Group B will be administered placebo implants on Days 0, 60 and 120
Read more
The number and severity of phototoxic reactions, the type and duration of sun exposure, treatment-emergent adverse events and the use of concomitant medication will be recorded by patients in study diaries between Days 0 and 180. Quality of life will be measured using the DLQI and EPP-QoL at Days 0, 60, 120 and 180. Participants will visit the clinic on Days 60, 120 and 180 for assessments of adverse events.
A subset of patients will be photoprovoked on the lower back and dorsal surface of the hand and the minimal symptom dose (MSD) will be determined on Days 0, 30, 60, 90 and 120.
Read the detailed description
Afamelanotide is a man-made drug being studied for use as a preventative medication for Erythropoietic Protoporphyria (EPP) sufferers. It is a synthetically produced analogue of human alpha melanocyte stimulating hormone (alpha-MSH) and is available in Europe.
The purpose of this study is to look at the type and duration of sun exposure 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 to be administered under the skin. The implant may contain the study drug afamelanotide or a placebo (inactive medication).
Over 620 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.
This study aims to confirm the photoprotective properties if afamelanotide demonstrated in the earlier Phase II and phase III studies.
- 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
One 16mg subcutaneous implant every 2 months for 6 months.
PlaceboDrug
One placebo subcutaneous implant every 2 months for 6 months
| Study group | Role | What they receive |
|---|---|---|
| Afamelanotide | Experimental | One 16mg subcutaneous implant every 2 months for 6 months. Receives: Drug: Afamelanotide |
| Placebo | Placebo comparator | One placebo subcutaneous implant every 2 months for 6 months. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of Direct Sunlight Exposure Between 10:00 and 18:00 Hours on Days When no Pain Was Experienced (Pain Score of 0).
The amount of direct sunlight exposure between 10:00 and 18:00 hours on days when no pain was experienced (e.g.11-point Likert pain score of 0). Time was recorded in a patient diary using 15 minute time blocks.
The pain score is measured by the 11-point Likert Pain scale with minimum of 0 and maximum of 10.
Likert Pain scale of 0 represents no pain and 10 represents worst imaginable pain.
Measured: Daily for 6 months
Secondary outcomes (6)
Combined Sun Exposure and Phototoxic Pain
Time in direct sunlight exposure between 10:00 and 18:00 hours on days when no or mild pain was experienced (Likert scores of 0 to 3).
The pain score is measured by the 11-point Likert Pain scale with minimum of 0 and maximum of 10.
Likert Pain scale of 0 represents no pain and 10 represents worst imaginable pain.
Measured: Daily for 6 months
Sun Exposure
Duration of direct sunlight exposure between 10:00 and 18:00 hours during the study.
Measured: Daily for 6 months
Quality of Life Score
The Quality of life of participant is measured using DLQI and EPP QoL. The Dermatology Life Quality Index (DLQI) is a simple practical measure for routine clinical use.
The DLQI ranges from 0 (no impact on life) to 30 (significant impact on life) . The Erthropoietic protoporphyria quality of life measure (EPP-QoL) scores range from 0 (worst imaginable QoL) to 100 (best possible QoL).
Measured: Day 60, Day 120, and Day 180 or early termination.
Photoprovocation
A subset of subjects was photoprovoked on the dorsal surface of the hand (predilection place) and lower back and the minimum symptom dose (MSD) determined on Days 0, 30, 60, 90 and 120.
The amount of radiation required to provoke the first clinical symptom was recorded.
Measured: Day 0, Day 30, Day 60, Day 90 and Day 120.
Maximum Severity of Phototoxic Reaction Experienced by Participants
The phototoxicity - phototoxic pain secondary endpoint has been divided into two secondary outcome measures.
The days on which the participant experienced pain as a result of phototoxic reactions (caused by exposure to natural light) was recorded in a study diary. On each day such a reaction occurred, the participant scored the level of pain using an 11-point Likert pain scale, with minimum of 0 and maximum of 10. The 11-point Likert pain scale with a value of 0 represents no pain and 10 represents worst imaginable pain.
The maximum severity of a phototoxic reaction was determined by the highest daily 11-point Likert scale score that occurred during that phototoxic reaction.
Measured: Daily for 6 months
Total Number Phototoxic Reactions Experienced by Participants
The phototoxicity - phototoxic pain secondary endpoint has been divided into two secondary outcome measures.
The number of episodes was the endpoint. The days on which the participant experienced pain as a result of phototoxic reactions (caused by exposure to natural light) was recorded in a study diary. On each day such a reaction occurred, the participant scored the level of pain using an 11-point Likert pain scale, with minimum of 0 and maximum of 10. The 11-point Likert Pain scale with a value of 0 represents no pain and 10 represents worst imaginable pain.
The number of phototoxic reactions was determined by counting the number of episodes on which participants report a 11-point Likert scale score of 4 or more for one or more consecutive days.
Measured: Daily for 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2012 (estimated)
- Study startMay 2012
- Primary completionJul 2013
- Study completionJul 2013
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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clinuvel Pharmaceuticals Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Robert Desnick, MD, Principal investigator, Mt. Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01605136
- Sponsor's protocol ID
- CUV039
- Status last verified
- Sep 2019
- First submitted
- 22 May 2012
- Last updated
- 19 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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 19 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Multicentre, Double-Blind, Randomized, Placebo-Controlled Study to Confirm the Safety and Efficacy of Subcutaneous Bioresorbable Afamelanotide Implants in Patients With Erythropoietic Protoporphyria (EPP)
- ClinicalTrials.gov ID
- NCT01605136
- Acronym / sponsor ID
- CUV039
- Conditions
- Erythropoietic Protoporphyria
- Keywords
- Erythropoietic Protoporphyria, EPP, Afamelanotide
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 93 participants (actual)
- Lead sponsor
- Clinuvel Pharmaceuticals LimitedIndustry (pharma, biotech, devices)
- Study start
- May 2012
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 24 May 2012 (estimated)
- Results
- Posted 26 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized placebo-controlled study to be conducted in two parallel study arms for a six month period (three doses). Between 75 and 100 eligible patients will be enrolled. Patients will receive afamelanotide (16 mg implants) or placebo according to the following dosing regimen:
- Group A will be administered afamelanotide implants on Days 0, 60 and 120
- Group B will be administered placebo implants on Days 0, 60 and 120
The number and severity of phototoxic reactions, the type and duration of sun exposure, treatment-emergent adverse events and the use of concomitant medication will be recorded by patients in study diaries between Days 0 and 180. Quality of life will be measured using the DLQI and EPP-QoL at Days 0, 60, 120 and 180. Participants will visit the clinic on Days 60, 120 and 180 for assessments of adverse events.
A subset of patients will be photoprovoked on the lower back and dorsal surface of the hand and the minimal symptom dose (MSD) will be determined on Days 0, 30, 60, 90 and 120.
Detailed description
Afamelanotide is a man-made drug being studied for use as a preventative medication for Erythropoietic Protoporphyria (EPP) sufferers. It is a synthetically produced analogue of human alpha melanocyte stimulating hormone (alpha-MSH) and is available in Europe.
The purpose of this study is to look at the type and duration of sun exposure 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 to be administered under the skin. The implant may contain the study drug afamelanotide or a placebo (inactive medication).
Over 620 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.
This study aims to confirm the photoprotective properties if afamelanotide demonstrated in the earlier Phase II and phase III studies.
Study design
- Primary purpose
- Treatment
- 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: AfamelanotideOne 16mg subcutaneous implant every 2 months for 6 months. |
| Placebo | Placebo comparator | Drug: PlaceboOne placebo subcutaneous implant every 2 months for 6 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male or female subjects with characteristic symptoms of EPP phototoxicity and a biochemically-confirmed diagnosis of EPP.
- Aged 18 years old and above (inclusive).
- Able to understand and sign the written Informed Consent Form.
- Willing to take precautions to prevent pregnancy until completion of the study (Day 180).
Key exclusion criteria (12 listed)
- Any allergy to afamelanotide or the polymer contained in the implant or to lidocaine or other local anesthetic to be used during the administration of the 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 polymorphic light eruption, actinic prurigo, discoid lupus erythematosus, chronic actinic dermatitis 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 |
|---|---|---|
| AfamelanotideOne 16mg subcutaneous implant every 2 months for 6 months. | Drug | Afamelanotide |
| PlaceboOne placebo subcutaneous implant every 2 months for 6 months | Drug | Placebo |
Primary outcome
Duration of Direct Sunlight Exposure Between 10:00 and 18:00 Hours on Days When no Pain Was Experienced (Pain Score of 0).
Time frame: Daily for 6 months
The amount of direct sunlight exposure between 10:00 and 18:00 hours on days when no pain was experienced (e.g.11-point Likert pain score of 0). Time was recorded in a patient diary using 15 minute time blocks. The pain score is measured by the 11-point Likert Pain scale with minimum of 0 and maximum of 10. Likert Pain scale of 0 represents no pain and 10 represents worst imaginable pain.
6 secondary outcomes
Combined Sun Exposure and Phototoxic Pain
Time frame: Daily for 6 months
Sun Exposure
Time frame: Daily for 6 months
Quality of Life Score
Time frame: Day 60, Day 120, and Day 180 or early termination.
Photoprovocation
Time frame: Day 0, Day 30, Day 60, Day 90 and Day 120.
Maximum Severity of Phototoxic Reaction Experienced by Participants
Time frame: Daily for 6 months
Total Number Phototoxic Reactions Experienced by Participants
Time frame: Daily for 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2019.
- 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.
Robert Desnick, MD principal investigator
Mt. Sinai Medical Center
7 sites in 1 country: 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 7 sites in United States.
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 4 inclusion and 12 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 19 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. 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 26 Aug 2019). 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?
Duration of Direct Sunlight Exposure Between 10:00 and 18:00 Hours on Days When no Pain Was Experienced (Pain Score of 0). (time frame: Daily for 6 months). 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 NCT01605136, 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 19 Sep 2019.