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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). Between 75 and 100 eligible patients will be enrolled. Patients will receive afamelanotide (16 mg implants) or placebo according to the following dosing regimen:
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Afamelanotide | Experimental | One 16mg subcutaneous implant every 2 months for 6 months. |
|
| Placebo | Placebo Comparator | One placebo subcutaneous implant every 2 months for 6 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Afamelanotide | Drug | One 16mg subcutaneous implant every 2 months for 6 months. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Daily for 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Daily for 6 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robert Desnick, MD | Mt. Sinai Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama | Birmingham | Alabama | 35294 | United States | ||
| University of California, San Francisco |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26132941 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Afamelanotide | One 16mg subcutaneous implant every 2 months for 6 months. Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months. |
| FG001 | Placebo | One placebo subcutaneous implant every 2 months for 6 months. Placebo: One placebo subcutaneous implant every 2 months for 6 months |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Study Period |
|
| |||||||||||||||||||||
| Safety Follow-Up Period |
|
Number of subjects enrolled into the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Afamelanotide | One 16mg subcutaneous implant every 2 months for 6 months. Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months. |
| BG001 | Placebo | One placebo subcutaneous implant every 2 months for 6 months. Placebo: One placebo subcutaneous implant every 2 months for 6 months |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | 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. | Number of subjects (ITT population, from Patient Diary Card) | Posted | Median | Full Range | hours | Daily for 6 months |
|
Visit 1 (Day 0) - Visit 4 (Day 180)
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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 | One 16mg subcutaneous implant every 2 months for 6 months. Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 15.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 15.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Dennis Wright | Clinuvel Inc. | 646 527 7310 | 170 | 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 |
|
| Sun Exposure | Duration of direct sunlight exposure between 10:00 and 18:00 hours during the study. | 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). | 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. | 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. | 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. | Daily for 6 months |
| San Francisco |
| California |
| 94143 |
| United States |
| Henry Ford Medical Center | Detroit | Michigan | 48202 | 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 | 84112 | United States |
| Lost to Follow-up |
|
| NOT COMPLETED |
|
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Placebo |
Placebo: One placebo subcutaneous implant every 2 months for 6 months |
|
|
| Secondary | 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. | Number of subjects (ITT population, from Patient Diary Card) | Posted | Median | Full Range | hours | Daily for 6 months |
|
|
|
| Secondary | Sun Exposure | Duration of direct sunlight exposure between 10:00 and 18:00 hours during the study. | Number of subjects (ITT population, from Patient Diary Card) | Posted | Median | Full Range | hours | Daily for 6 months |
|
|
|
| Secondary | 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). | The number of participants analyzed differs from the overall number of participants analyzed because the data was either incomplete and/or missing. Only data from those who completed the Quality of Life assessments are included at each time point. | Posted | Median | Full Range | units on a scale | Day 60, Day 120, and Day 180 or early termination. |
|
|
|
| Secondary | 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. | Posted | Median | Full Range | J/cm^2 | Day 0, Day 30, Day 60, Day 90 and Day 120. |
|
|
|
| Secondary | 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. | Posted | Median | Full Range | score on a scale | Daily for 6 months |
|
|
|
| Secondary | 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. | Posted | Median | Full Range | episodes | Daily for 6 months |
|
|
|
| 3 |
| 48 |
| 45 |
| 48 |
| EG001 | Placebo | One placebo subcutaneous implant every 2 months for 6 months. Placebo: One placebo subcutaneous implant every 2 months for 6 months | 2 | 45 | 39 | 45 |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Malignant melanoma in situ | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Non-systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Melanocytic naevus | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 15.1 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Implant site discolouration | General disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA 15.1 | Non-systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 15.1 | Non-systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 15.1 | Non-systematic Assessment |
|
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Non-systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA 15.1 | 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 |
| DLQI - Day 60 |
|
|
| DLQI - Day 120 |
|
|
| DLQI - Day 180/Early Termination |
|
|
| EPP QOL - Day 0 (baseline) |
|
|
| EPP QOL - Day 60 |
|
|
| EPP QOL - Day 120 |
|
|
| EPP QOL - Day 180/Early Termination |
|
|
| Change at Day 60: dorsal surface of the hand |
|
| Change at Day 90: dorsal surface of the hand |
|
| Change at Day 120: dorsal surface of the hand |
|
| Day 0: lower back |
|
| Change at Day 30: lower back |
|
| Change at Day 60: lower back |
|
| Change at Day 90: lower back |
|
| Change at Day 120: lower back |
|