Erythropoietic ProtoporphyriaPhase 2NCT01097044
Phase II Confirmatory Study in Erythropoietic Protoporphyria (EPP)
A Phase 2 study testing Afamelanotide in people with Erythropoietic Protoporphyria, run by Clinuvel Pharmaceuticals Limited at 6 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). Approximately 10 eligible patients per center will be enrolled and will receive afamelanotide (16 mg implants) or placebo according to the following dosing regimen: Group A will be… 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
- 77 participants
- Where
- 6 sitesUnited States
- Study dates
- Apr 2010to Apr 2011
- Phase
- Phase 2
- 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 photosensitivity of EPP symptoms and positive diagnosis of EPP confirmed by laboratory result of elevated total protoporphyrin IX.
- 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 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.
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 within 60 days prior to the screening visit.
- 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
6 sites in 1 country.
6 sites in 1 country
United States6 sites
University of Alabama
Birmingham, Alabama, 35294
Carolina's Medical Center Cannon Research
Charlotte, North Carolina, 29203
University of Texas
Galveston, Texas, 77555
Mt. Sinai
New York, New York, 10029
University of Utah
Salt Lake City, Utah, 84132
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: A Phase II, Multicentre, Double-Blind, Randomised, 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). Approximately 10 eligible patients per center will be enrolled and 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
To determine eligibility for study inclusion, patients will undergo a screening evaluation 7 to 14 days prior to the administration of the first dose. The number and severity of phototoxic reactions will be determined Days 60, 120, and 180. Quality of life will be measured using the EPP specific questionnaire (EPP-QoL) every 60 days and the DLQI questionnaire every 7 days, beginning at Day 0 until Day 180. Participants will visit the clinic on Days 60, 120 and 180 for assessments of adverse events.
Read the detailed description
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 between 10:00 and 20:00 hours. 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 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.
- 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. (3 implants in total)
PlaceboDrug
One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total)
| Study group | Role | What they receive |
|---|---|---|
| Afamelanotide | Experimental | Dose: 16 mg implant; release of 16 mg over 7 to 10 days Mode of administration: Subcutaneous implantation Frequency: Every 60 days (on Days 0, 60 and 120) Receives: Drug: Afamelanotide |
| Placebo | Placebo comparator | Dose: 16 mg implant; Mode of administration: Subcutaneous implantation Frequency: Every 60 days (on Days 0, 60 and 120) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time in Direct Sunlight Between 10:00-15:00 on Pain-free Days
The amount of direct sunlight exposure between 10:00 and 15:00 hours on days when no pain was experienced (e.g. 11-point Likert pain score of 0). Time was recorded in a patient dairy 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)
Maximum Severity of Phototoxic Reaction Experienced by Participants
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
Quality of Life Measured by Participant Completed Questionnaire
Erythropoietic Protoporphyria Quality of Life Measure (EPP-QoL) is used to measure the quality of life of participants.
The total EPP-QoL score ranges from 0 to 100, with a score of 0 as the worst quality of life and score of 100 as the best quality of life.
Measured: Day 0, Day 60, Day 120, Day 180
Change of Total Protoporphyrin IX Level in Participants
This was an exploratory assessment only to analyze whether afamelanotide-induced change in sun exposure would result in a reduction of protoporphyrin IX.
The changes of the Total Protoporphyrin IX Level (μg/dL) from Screening Visit (ITT Population) were measured between the two groups.
The Protoporphyrin IX level is a laboratory parameter that is measured in specialist labs.
Measured: Baseline, Day 60, Day 120, Day 180
Number of Participants With Phototoxic Reactions With Likert Severity Scores ≥ 4 and ≥ 7
The number of participants who experienced phototoxic reactions with Likert severity scores ≥ 4 and severity scores ≥7 were recorded.
A derived endpoint was used. The number of participants who reported at least one phototoxic reaction with a Likert severity score of ≥ 4 was recorded. For severity scores ≥ 7, the number of patients who reported at least one phototoxic reaction with a Likert severity score of ≥ 7 was recorded.
The 11-point Likert pain scale ranges from minimum of 0 to maximum of 10. The 11-point Likert pain scale with a value of 0 represents no pain and 10 represents worst imaginable pain.
Measured: Daily for 6 months
Number of Phototoxic Reactions Experienced by Participants
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
Total Severity of Phototoxic Reactions Experienced by Participants Over the Entire Study
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 total severity of phototoxic reactions was determined by the sum of daily 11-point Likert scale scores that occurred during phototoxic reactions. The overall sum of the severity per participant over the entire study was analyzed. The theoretical minimum score is 0 and the maximum possible score is 1800.
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 posted1 Apr 2010 (estimated)
- Study startApr 2010
- Primary completionApr 2011
- Study completionApr 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.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 77 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01097044
- Sponsor's protocol ID
- CUV030
- Status last verified
- Oct 2019
- First submitted
- 30 Mar 2010
- Last updated
- 28 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, 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
- NCT01097044
- Acronym / sponsor ID
- CUV030
- Conditions
- Erythropoietic Protoporphyria
- Keywords
- Erythropoietic Protoporphyria, EPP, Afamelanotide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 77 participants (actual)
- Lead sponsor
- Clinuvel Pharmaceuticals LimitedIndustry (pharma, biotech, devices)
- Study start
- Apr 2010
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 1 Apr 2010 (estimated)
- Results
- Posted 17 Sep 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). Approximately 10 eligible patients per center will be enrolled and 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
To determine eligibility for study inclusion, patients will undergo a screening evaluation 7 to 14 days prior to the administration of the first dose. The number and severity of phototoxic reactions will be determined Days 60, 120, and 180. Quality of life will be measured using the EPP specific questionnaire (EPP-QoL) every 60 days and the DLQI questionnaire every 7 days, beginning at Day 0 until Day 180. Participants will visit the clinic on Days 60, 120 and 180 for assessments of adverse events.
Detailed description
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 between 10:00 and 20:00 hours. 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 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.
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: AfamelanotideDose: 16 mg implant; release of 16 mg over 7 to 10 days Mode of administration: Subcutaneous implantation Frequency: Every 60 days (on Days 0, 60 and 120) |
| Placebo | Placebo comparator | Drug: PlaceboDose: 16 mg implant; Mode of administration: Subcutaneous implantation Frequency: Every 60 days (on Days 0, 60 and 120) |
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 photosensitivity of EPP symptoms and positive diagnosis of EPP confirmed by laboratory result of elevated total protoporphyrin IX.
- 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 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 |
|---|---|---|
| AfamelanotideOne 16mg subcutaneous implant every 2 months for 6 months. (3 implants in total) | Drug | Afamelanotide |
| PlaceboOne placebo subcutaneous implant every 2 months for 6 months. (3 implants in total) | Drug | Placebo |
Primary outcome
Time in Direct Sunlight Between 10:00-15:00 on Pain-free Days
Time frame: Daily for 6 months
The amount of direct sunlight exposure between 10:00 and 15:00 hours on days when no pain was experienced (e.g. 11-point Likert pain score of 0). Time was recorded in a patient dairy 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
Maximum Severity of Phototoxic Reaction Experienced by Participants
Time frame: Daily for 6 months
Quality of Life Measured by Participant Completed Questionnaire
Time frame: Day 0, Day 60, Day 120, Day 180
Change of Total Protoporphyrin IX Level in Participants
Time frame: Baseline, Day 60, Day 120, Day 180
Number of Participants With Phototoxic Reactions With Likert Severity Scores ≥ 4 and ≥ 7
Time frame: Daily for 6 months
Number of Phototoxic Reactions Experienced by Participants
Time frame: Daily for 6 months
Total Severity of Phototoxic Reactions Experienced by Participants Over the Entire Study
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 28 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Afamelanotide in people with Erythropoietic Protoporphyria, run by Clinuvel Pharmaceuticals Limited at 6 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 28 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 17 Sep 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?
Time in Direct Sunlight Between 10:00-15:00 on Pain-free Days (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?
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 28 Oct 2019.