Erythropoietic Protoporphyria
Conditions
Keywords
Erythropoietic Protoporphyria, EPP, Afamelanotide
Brief summary
This was a phase III, multicentre, randomised, double-blind, placebo-controlled study, to evaluate the safety and efficacy of subcutaneous bioresorbable afamelanotide implants in patients with Erythropoietic Protoporphyria (EPP). The study was conducted with two parallel study arms with crossover between treatments every 60 days. Eligible patients were randomised to a treatment group, and received implants of active treatment (afamelanotide 16mg) or placebo, in an alternating crossover fashion according to the following dosing regime: * Group A was administered active implants on Days 0, 120, 240 and placebo implants on Days 60, 180, 300 * Group B was administered placebo implants on Days 0, 120, 240 and active implants on Days 60, 180, 300
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). 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). This study aims to provide insight into the effectiveness of afamelanotide under normal conditions of use in EPP patients.
Interventions
DRUGAfamelanotide
16mg subcutaneous implant
DRUGPlacebo
Placebo subcutaneous implant
Sponsors
Clinuvel Pharmaceuticals Limited
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male or female patients 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. * Written informed consent prior to the performance of any study-specific procedure.
Exclusion criteria
* Any allergy to afamelanotide or the polymer contained in the implant or to lignocaine or other local anaesthetic 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. * Diagnosed with HIV/AIDS or hepatitis. * Any evidence of clinically significant organ dysfunction or any clinically significant deviation from normal in the clinical or laboratory determinations. * Acute history of drug or alcohol abuse (in the last 12 months). * History of disorders of the gastrointestinal, hepatic, renal, cardiovascular, respiratory, endocrine (including diabetes, Cushing's syndrome, Addison's disease, Peutz-Jeagher syndrome), neurological (including seizures), haematological (especially anaemia of less than 10 g/100 mL) or systemic disease judged to be clinically significant by the Investigator. * Major medical or psychiatric illness * 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 was 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). * Participation in a clinical trial of an investigational agent within 30 days prior to the screening visit. * Use of regular medications as specified in protocol Section 5.4 Prior and Concomitant Therapy. * Any factors that may affect skin reflectance measurements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Number of Days of Phototoxic Reactions (Study Efficacy Population) | 0-360 days or Early Termination | The cumulative number of days where a phototoxic reaction occurred was recorded in the patient diary. The reported data represent a cumulative total for days of phototoxic reactions. 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 primary analysis population for efficacy was revised, to analyze only participants who reported cumulative total Likert pain scores of at least 26 during the study (0-360 days). This population, which was comprised of 60 patients, is identified as the Efficacy population. Participants with less than 26 Likert pain scores were not included in the analysis. |
| The Mean Number of Phototoxic Reactions (Study Efficacy Population) | 0-360 days or Early Termination | The mean number of phototoxic reactions that occurred whilst patients were on active compared with placebo implants. 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 primary analysis population for efficacy was revised, to analyze only participants who reported a cumulative total Likert pain score of at least 26 during the study (0-360 days). This population, which was comprised of 60 patients, is identified as the Efficacy population. Participants with less than 26 Likert pain scores were not included in the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Number of Days With Sunlight Exposure (Study Efficacy Population) | 0-360 days or Early Termination | The number of days with sunlight exposure was recorded in the patient diary. The sunlight exposures were divided into the following categories: none, \< 1 hour, 1 to 3 hours, 3 to 6 hours and \> 6 hours per day. |
| Skin Melanin Density (Study Completers Population) | Day0, Day14, Day30, Day60, Day74, Day90, Day120, Day150, Day180, Day210, Day240, Day270, Day300, Day330, Day360 or Early Termination | Changes in melanin density (MD) (measured by spectrophotometry) at each visit by group. Participants had their skin pigmentation measured by a non-invasive quantitative skin chromaticity (reflectance) reading. Reflectance by the skin of light measured at the wavelengths of 400 nm and 420 nm was recorded using a Minolta cm-2500d spectrophotometer at the following skin sites: forehead, left cheek, right inside upper arm, left medial forearm, right side of abdomen (avoiding implant insertion site), left side of sacral region/buttock. Melanin density was determined for each skin site using the method of Dwyer et al 1998. |
| Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population | Day0, Day60, Day120, Day180, Day240, Day300, Day360 or Early Termination | The Summary of SF36 change from Baseline of Physical Component Score (PCS) to the scores during treatment on Days 60, 120, 180, 240, 300 and 360 using the SF36 questionnaire. The SF-36 (The Short Form 36 Health Survey) consists of eight scaled scores, which are the weighted sums of the questions in each section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The higher scores represent better health-related quality-of-life. |
| Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population | Day0, Day60, Day120, Day180, Day240, Day300, Day360 or Early Termination | The Summary of SF36 change from Baseline of Mental Component Score (MCS) to the scores during treatment on Days 60, 120, 180, 240, 300 and 360 using the SF36 questionnaire. The SF-36 (The Short Form 36 Health Survey) consists of eight scaled scores, which are the weighted sums of the questions in each section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The higher scores represent better health-related quality-of-life. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A Group A was administered active implants on Days 0, 120, 240 and placebo implants on Days 60, 180, 300
Afamelanotide: 16mg subcutaneous implant
Placebo: Placebo subcutaneous implant | 49 |
| Group B Group B was administered placebo implants on Days 0, 120, 240 and active implants on Days 60, 180, 300
Afamelanotide: 16mg subcutaneous implant
Placebo: Placebo subcutaneous implant | 51 |
| Total | 100 |
Baseline characteristics
| Characteristic | Group B | Total | Group A |
|---|---|---|---|
| Age, Customized Age | 39.2 years STANDARD_DEVIATION 12.4 | 38.9 years STANDARD_DEVIATION 12.8 | 38.5 years STANDARD_DEVIATION 13.3 |
| Race/Ethnicity, Customized Caucasian | 50 Participants | 99 Participants | 49 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Female | 23 Participants | 53 Participants | 30 Participants |
| Sex: Female, Male Male | 28 Participants | 47 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 94 / 100 | 88 / 100 |
| serious Total, serious adverse events | 3 / 100 | 3 / 100 |
Outcome results
Primary
Cumulative Number of Days of Phototoxic Reactions (Study Efficacy Population)
The cumulative number of days where a phototoxic reaction occurred was recorded in the patient diary. The reported data represent a cumulative total for days of phototoxic reactions. 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 primary analysis population for efficacy was revised, to analyze only participants who reported cumulative total Likert pain scores of at least 26 during the study (0-360 days). This population, which was comprised of 60 patients, is identified as the Efficacy population. Participants with less than 26 Likert pain scores were not included in the analysis.
Time frame: 0-360 days or Early Termination
Population: Participants who reported a cumulative total Likert pain score of at least 26 during the study (0-360 days), which was comprised of 60 patients, is identified as the Efficacy population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Afamelanotide | Cumulative Number of Days of Phototoxic Reactions (Study Efficacy Population) | Severe Pain | 39 Days |
| Afamelanotide | Cumulative Number of Days of Phototoxic Reactions (Study Efficacy Population) | Moderate Pain | 129 Days |
| Afamelanotide | Cumulative Number of Days of Phototoxic Reactions (Study Efficacy Population) | Mild Pain | 1126 Days |
| Afamelanotide | Cumulative Number of Days of Phototoxic Reactions (Study Efficacy Population) | No Pain | 8650 Days |
| Placebo | Cumulative Number of Days of Phototoxic Reactions (Study Efficacy Population) | No Pain | 8484 Days |
| Placebo | Cumulative Number of Days of Phototoxic Reactions (Study Efficacy Population) | Severe Pain | 45 Days |
| Placebo | Cumulative Number of Days of Phototoxic Reactions (Study Efficacy Population) | Mild Pain | 1237 Days |
| Placebo | Cumulative Number of Days of Phototoxic Reactions (Study Efficacy Population) | Moderate Pain | 179 Days |
Primary
The Mean Number of Phototoxic Reactions (Study Efficacy Population)
The mean number of phototoxic reactions that occurred whilst patients were on active compared with placebo implants. 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 primary analysis population for efficacy was revised, to analyze only participants who reported a cumulative total Likert pain score of at least 26 during the study (0-360 days). This population, which was comprised of 60 patients, is identified as the Efficacy population. Participants with less than 26 Likert pain scores were not included in the analysis.
Time frame: 0-360 days or Early Termination
Population: The result is reported in a per sequence format with the different time points at which the interventions were switched.~Total of 60 Participants: 32 participants in Group A and 28 participants in Group B.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Afamelanotide | The Mean Number of Phototoxic Reactions (Study Efficacy Population) | Day 0 | 1.44 counts of episodes | Standard Deviation 3.25 |
| Afamelanotide | The Mean Number of Phototoxic Reactions (Study Efficacy Population) | Day 60 | 0.56 counts of episodes | Standard Deviation 1.87 |
| Afamelanotide | The Mean Number of Phototoxic Reactions (Study Efficacy Population) | Day 120 | 1.09 counts of episodes | Standard Deviation 2.08 |
| Afamelanotide | The Mean Number of Phototoxic Reactions (Study Efficacy Population) | Day 180 | 0.32 counts of episodes | Standard Deviation 2.07 |
| Afamelanotide | The Mean Number of Phototoxic Reactions (Study Efficacy Population) | Day 240 | 0.63 counts of episodes | Standard Deviation 1.52 |
| Afamelanotide | The Mean Number of Phototoxic Reactions (Study Efficacy Population) | Day 300 | 0.72 counts of episodes | Standard Deviation 1.42 |
| Placebo | The Mean Number of Phototoxic Reactions (Study Efficacy Population) | Day 240 | 2.21 counts of episodes | Standard Deviation 3.57 |
| Placebo | The Mean Number of Phototoxic Reactions (Study Efficacy Population) | Day 0 | 2.64 counts of episodes | Standard Deviation 5.33 |
| Placebo | The Mean Number of Phototoxic Reactions (Study Efficacy Population) | Day 180 | 0.78 counts of episodes | Standard Deviation 0.61 |
| Placebo | The Mean Number of Phototoxic Reactions (Study Efficacy Population) | Day 60 | 0.11 counts of episodes | Standard Deviation 0.31 |
| Placebo | The Mean Number of Phototoxic Reactions (Study Efficacy Population) | Day 300 | 1.96 counts of episodes | Standard Deviation 4.53 |
| Placebo | The Mean Number of Phototoxic Reactions (Study Efficacy Population) | Day 120 | 0.79 counts of episodes | Standard Deviation 2.25 |
Secondary
Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population
The Summary of SF36 change from Baseline of Mental Component Score (MCS) to the scores during treatment on Days 60, 120, 180, 240, 300 and 360 using the SF36 questionnaire. The SF-36 (The Short Form 36 Health Survey) consists of eight scaled scores, which are the weighted sums of the questions in each section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The higher scores represent better health-related quality-of-life.
Time frame: Day0, Day60, Day120, Day180, Day240, Day300, Day360 or Early Termination
Population: The secondary analysis population for efficacy included those subjects who received all required doses of investigational product. This population, which was comprised of 93 patients, is identified as the study completers population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Afamelanotide | Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population | Day 120 | 53.16 score on a scale | Standard Deviation 7.34 |
| Afamelanotide | Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population | Day 240 | 51.96 score on a scale | Standard Deviation 8.48 |
| Afamelanotide | Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population | Day 60 | 52.31 score on a scale | Standard Deviation 9.58 |
| Afamelanotide | Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population | Day 300 | 52.99 score on a scale | Standard Deviation 9.21 |
| Afamelanotide | Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population | Day 180 | 53.84 score on a scale | Standard Deviation 7.12 |
| Afamelanotide | Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population | Day 360 | 52.44 score on a scale | Standard Deviation 8.13 |
| Afamelanotide | Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population | Day 0 | 51.41 score on a scale | Standard Deviation 6.61 |
| Placebo | Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population | Day 360 | 52.23 score on a scale | Standard Deviation 8 |
| Placebo | Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population | Day 0 | 53.03 score on a scale | Standard Deviation 6.75 |
| Placebo | Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population | Day 60 | 52.26 score on a scale | Standard Deviation 7.46 |
| Placebo | Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population | Day 120 | 52.71 score on a scale | Standard Deviation 7.39 |
| Placebo | Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population | Day 180 | 52.06 score on a scale | Standard Deviation 7.5 |
| Placebo | Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population | Day 240 | 52.34 score on a scale | Standard Deviation 8.07 |
| Placebo | Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population | Day 300 | 52.76 score on a scale | Standard Deviation 7.61 |
Secondary
Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population
The Summary of SF36 change from Baseline of Physical Component Score (PCS) to the scores during treatment on Days 60, 120, 180, 240, 300 and 360 using the SF36 questionnaire. The SF-36 (The Short Form 36 Health Survey) consists of eight scaled scores, which are the weighted sums of the questions in each section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The higher scores represent better health-related quality-of-life.
Time frame: Day0, Day60, Day120, Day180, Day240, Day300, Day360 or Early Termination
Population: The secondary analysis population for efficacy included those subjects who received all required doses of investigational product. This population, which was comprised of 93 patients, is identified as the study completers population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Afamelanotide | Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population | Day 120 | 54.26 score on a scale | Standard Deviation 5.53 |
| Afamelanotide | Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population | Day 240 | 53.19 score on a scale | Standard Deviation 7.09 |
| Afamelanotide | Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population | Day 60 | 54.20 score on a scale | Standard Deviation 5.99 |
| Afamelanotide | Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population | Day 300 | 53.48 score on a scale | Standard Deviation 5.71 |
| Afamelanotide | Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population | Day 180 | 53.39 score on a scale | Standard Deviation 5.88 |
| Afamelanotide | Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population | Day 360 | 52.30 score on a scale | Standard Deviation 6.03 |
| Afamelanotide | Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population | Day 0 | 51.90 score on a scale | Standard Deviation 7.05 |
| Placebo | Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population | Day 360 | 54.88 score on a scale | Standard Deviation 5.01 |
| Placebo | Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population | Day 0 | 54.22 score on a scale | Standard Deviation 5.48 |
| Placebo | Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population | Day 60 | 54.85 score on a scale | Standard Deviation 5.59 |
| Placebo | Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population | Day 120 | 54.68 score on a scale | Standard Deviation 5.78 |
| Placebo | Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population | Day 180 | 53.72 score on a scale | Standard Deviation 5.59 |
| Placebo | Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population | Day 240 | 54.25 score on a scale | Standard Deviation 5.22 |
| Placebo | Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population | Day 300 | 53.88 score on a scale | Standard Deviation 4.93 |
Secondary
Cumulative Number of Days With Sunlight Exposure (Study Efficacy Population)
The number of days with sunlight exposure was recorded in the patient diary. The sunlight exposures were divided into the following categories: none, \< 1 hour, 1 to 3 hours, 3 to 6 hours and \> 6 hours per day.
Time frame: 0-360 days or Early Termination
Population: The primary analysis population for efficacy was revised, with an additional criterion of a total cumulative pain score of at least 26, and omitting patients who did not complete the study. This population, which was comprised of 60 patients, is identified as the Efficacy population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Afamelanotide | Cumulative Number of Days With Sunlight Exposure (Study Efficacy Population) | 3 - 6 hrs per day | 969 Days |
| Afamelanotide | Cumulative Number of Days With Sunlight Exposure (Study Efficacy Population) | < 1 hr per day | 1468 Days |
| Afamelanotide | Cumulative Number of Days With Sunlight Exposure (Study Efficacy Population) | 1 - 3 hrs per day | 2810 Days |
| Afamelanotide | Cumulative Number of Days With Sunlight Exposure (Study Efficacy Population) | None per day | 4358 Days |
| Afamelanotide | Cumulative Number of Days With Sunlight Exposure (Study Efficacy Population) | > 6 hrs per day | 339 Days |
| Placebo | Cumulative Number of Days With Sunlight Exposure (Study Efficacy Population) | None per day | 4582 Days |
| Placebo | Cumulative Number of Days With Sunlight Exposure (Study Efficacy Population) | > 6 hrs per day | 250 Days |
| Placebo | Cumulative Number of Days With Sunlight Exposure (Study Efficacy Population) | 3 - 6 hrs per day | 854 Days |
| Placebo | Cumulative Number of Days With Sunlight Exposure (Study Efficacy Population) | 1 - 3 hrs per day | 2695 Days |
| Placebo | Cumulative Number of Days With Sunlight Exposure (Study Efficacy Population) | < 1 hr per day | 1564 Days |
Secondary
Skin Melanin Density (Study Completers Population)
Changes in melanin density (MD) (measured by spectrophotometry) at each visit by group. Participants had their skin pigmentation measured by a non-invasive quantitative skin chromaticity (reflectance) reading. Reflectance by the skin of light measured at the wavelengths of 400 nm and 420 nm was recorded using a Minolta cm-2500d spectrophotometer at the following skin sites: forehead, left cheek, right inside upper arm, left medial forearm, right side of abdomen (avoiding implant insertion site), left side of sacral region/buttock. Melanin density was determined for each skin site using the method of Dwyer et al 1998.
Time frame: Day0, Day14, Day30, Day60, Day74, Day90, Day120, Day150, Day180, Day210, Day240, Day270, Day300, Day330, Day360 or Early Termination
Population: The secondary analysis population for efficacy included those subjects who received all required doses of investigational product. This population is identified as the study completers population.~Calculated MD \<0 or \>6 were omitted.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Afamelanotide | Skin Melanin Density (Study Completers Population) | Day 0 | 3.42 unitless | Standard Deviation 0.83 |
| Afamelanotide | Skin Melanin Density (Study Completers Population) | Day 14 | 3.75 unitless | Standard Deviation 0.77 |
| Afamelanotide | Skin Melanin Density (Study Completers Population) | Day 30 | 3.86 unitless | Standard Deviation 0.72 |
| Afamelanotide | Skin Melanin Density (Study Completers Population) | Day 60 | 3.80 unitless | Standard Deviation 0.77 |
| Afamelanotide | Skin Melanin Density (Study Completers Population) | Day 74 | 3.70 unitless | Standard Deviation 0.85 |
| Afamelanotide | Skin Melanin Density (Study Completers Population) | Day 90 | 3.67 unitless | Standard Deviation 0.8 |
| Afamelanotide | Skin Melanin Density (Study Completers Population) | Day 120 | 3.52 unitless | Standard Deviation 0.79 |
| Afamelanotide | Skin Melanin Density (Study Completers Population) | Day 150 | 3.79 unitless | Standard Deviation 0.82 |
| Afamelanotide | Skin Melanin Density (Study Completers Population) | Day 180 | 3.84 unitless | Standard Deviation 0.74 |
| Afamelanotide | Skin Melanin Density (Study Completers Population) | Day 210 | 3.76 unitless | Standard Deviation 0.76 |
| Afamelanotide | Skin Melanin Density (Study Completers Population) | Day 240 | 3.68 unitless | Standard Deviation 0.81 |
| Afamelanotide | Skin Melanin Density (Study Completers Population) | Day 270 | 3.97 unitless | Standard Deviation 0.72 |
| Afamelanotide | Skin Melanin Density (Study Completers Population) | Day 300 | 3.89 unitless | Standard Deviation 0.72 |
| Afamelanotide | Skin Melanin Density (Study Completers Population) | Day 330 | 3.82 unitless | Standard Deviation 0.73 |
| Afamelanotide | Skin Melanin Density (Study Completers Population) | Day 360 | 3.73 unitless | Standard Deviation 0.69 |
| Placebo | Skin Melanin Density (Study Completers Population) | Day 240 | 3.89 unitless | Standard Deviation 0.73 |
| Placebo | Skin Melanin Density (Study Completers Population) | Day 0 | 3.22 unitless | Standard Deviation 1.01 |
| Placebo | Skin Melanin Density (Study Completers Population) | Day 150 | 3.57 unitless | Standard Deviation 0.89 |
| Placebo | Skin Melanin Density (Study Completers Population) | Day 14 | 3.39 unitless | Standard Deviation 0.95 |
| Placebo | Skin Melanin Density (Study Completers Population) | Day 360 | 3.97 unitless | Standard Deviation 0.69 |
| Placebo | Skin Melanin Density (Study Completers Population) | Day 30 | 3.40 unitless | Standard Deviation 1.01 |
| Placebo | Skin Melanin Density (Study Completers Population) | Day 180 | 3.50 unitless | Standard Deviation 0.89 |
| Placebo | Skin Melanin Density (Study Completers Population) | Day 300 | 3.76 unitless | Standard Deviation 0.72 |
| Placebo | Skin Melanin Density (Study Completers Population) | Day 60 | 3.34 unitless | Standard Deviation 1 |
| Placebo | Skin Melanin Density (Study Completers Population) | Day 270 | 3.81 unitless | Standard Deviation 0.72 |
| Placebo | Skin Melanin Density (Study Completers Population) | Day 74 | 3.71 unitless | Standard Deviation 0.89 |
| Placebo | Skin Melanin Density (Study Completers Population) | Day 210 | 3.93 unitless | Standard Deviation 0.75 |
| Placebo | Skin Melanin Density (Study Completers Population) | Day 90 | 3.75 unitless | Standard Deviation 0.87 |
| Placebo | Skin Melanin Density (Study Completers Population) | Day 330 | 4.08 unitless | Standard Deviation 0.63 |
| Placebo | Skin Melanin Density (Study Completers Population) | Day 120 | 3.71 unitless | Standard Deviation 0.83 |