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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:
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
|
| Placebo | Placebo Comparator | Dose: 16 mg implant; Mode of administration: Subcutaneous implantation Frequency: Every 60 days (on Days 0, 60 and 120) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Afamelanotide | Drug | One 16mg subcutaneous implant every 2 months for 6 months. (3 implants in total) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Daily for 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robert Desnick, MD | Mt. Sinai | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama | Birmingham | Alabama | 35294 | United States | ||
| University of California, San Francisco |
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Study Recruitment period: April2010 - July2010
Study site location:
Mt. Sinai, New York Carolinas Medical Center, North Carolina University of Alabama at Birmingham, Alabama University of Utah, Utah University of Texas Medical Branch, Texas University of California, San Francisco, California
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| ID | Title | Description |
|---|---|---|
| FG000 | Afamelanotide | Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months. (3 implants in total) |
| FG001 | Placebo | Placebo: One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Afamelanotide | Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months. (3 implants in total) |
| BG001 | Placebo | Placebo: One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | One active participant and one placebo participant withdrew after Baseline assessment and no data was provided for the analysis of this endpoint. The overall number of participants analyzed differs from the total number of study participants because the data was either incomplete and/or missing. | Posted | Median | Full Range | Hours | Daily for 6 months |
|
6 months (180 days)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Afamelanotide | Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months. (3 implants in total) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| CRAMPY ABDOMINAL PAIN | Gastrointestinal disorders | MedDRA Version: 13 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA Version: 13.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Dennis Wright, Acting Chief Scientific Officer | Clinuvel Pharmaceuticals Limited | 646 527 7310 | Dennis.Wright@clinuvel.com |
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| ID | Term |
|---|---|
| D046351 | Protoporphyria, Erythropoietic |
| ID | Term |
|---|---|
| D017094 | Porphyrias, Hepatic |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D012873 | Skin Diseases, Genetic |
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| ID | Term |
|---|---|
| C534526 | afamelanotide |
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| Placebo | Drug | One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total) |
|
| 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. | 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. | 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. | 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. | 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. | Daily for 6 months. |
| San Francisco |
| California |
| 94143 |
| United States |
| Mt. Sinai | New York | New York | 10029 | United States |
| Carolina's Medical Center Cannon Research | Charlotte | North Carolina | 29203 | United States |
| University of Texas | Galveston | Texas | 77555 | United States |
| University of Utah | Salt Lake City | Utah | 84132 | United States |
| Withdrawal by Sponsor |
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Age, Categorical | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Placebo | Placebo: One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total) |
|
|
| Secondary | 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. | One active participant and one placebo participant withdrew after Baseline assessment and no data was provided for the analysis of this endpoint. The overall number of participants analyzed differs from the total number of study participants because the data was either incomplete and/or missing. | Posted | Median | Full Range | score on a scale | Daily for 6 months |
|
|
|
| Secondary | 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. | One active participant and one placebo participant withdrew after Baseline assessment and no data was provided for the analysis of this endpoint. The overall number of participants analyzed differs from the total number of study participants because the data was either incomplete and/or missing. | Posted | Median | Full Range | units on a scale | Day 0, Day 60, Day 120, Day 180 |
|
|
|
| Secondary | 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. | One active participant and one placebo participant withdrew after Baseline assessment and no data was provided for the analysis of this endpoint. The overall number of participants analyzed differs from the total number of study participants because the data was either incomplete and/or missing. | Posted | Mean | Standard Deviation | mcg/dL | Baseline, Day 60, Day 120, Day 180 |
|
|
|
| Secondary | 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. | One active participant and one placebo participant withdrew after Baseline assessment and no data was provided for the analysis of this endpoint. The overall number of participants analyzed differs from the total number of study participants because the data was either incomplete and/or missing. | Posted | Number | Count of Participants | Daily for 6 months |
|
|
|
| Secondary | 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. | One active participant and one placebo participant withdrew after Baseline assessment and no data was provided for the analysis of this endpoint. The overall number of participants analyzed differs from the total number of study participants because the data was either incomplete and/or missing. | Posted | Median | Full Range | Episodes | Daily for 6 months |
|
|
|
| Secondary | 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. | One active participant and one placebo participant withdrew after Baseline assessment and no data was provided for the analysis of this endpoint. The overall number of participants analyzed differs from the total number of study participants because the data was either incomplete and/or missing. | Posted | Mean | Standard Deviation | units on a scale | Daily for 6 months. |
|
|
|
| 2 |
| 39 |
| 31 |
| 39 |
| EG001 | Placebo | Placebo: One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total) | 2 | 38 | 29 | 38 |
| DIZZINESS | Nervous system disorders | MedDRA Version: 13 | Non-systematic Assessment |
|
| Low Pulse Rate | Cardiac disorders | MedDRA Version: 13 | Non-systematic Assessment |
|
| RECURRENT RECTAL BLEEDING | Gastrointestinal disorders | MedDRA Version: 13 | Non-systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA Version: 13.1 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA Version: 13.1 | Non-systematic Assessment |
|
| Implant Site Pain | General disorders | MedDRA Version: 13.1 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA Version: 13.1 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA Version: 13.1 | Non-systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA Version: 13.1 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version: 13.1 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA Version: 13.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA Version: 13.1 | Non-systematic Assessment |
|
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| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D011164 | Porphyrias |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| Day 60 |
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| Day 120 |
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| Day 180 |
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| Day 120 |
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| Day 180 |
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