Back to resultsMulticentre Phase III Erythropoietic Protoporphyria Study
Primary Purpose
Erythropoietic Protoporphyria
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Afamelanotide
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Erythropoietic Protoporphyria focused on measuring Erythropoietic Protoporphyria, EPP, Afamelanotide
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Group A
Group B
Arm Description
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
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
Full Information
NCT ID
NCT04053270
First Posted
August 8, 2019
Last Updated
October 8, 2019
Sponsor
Clinuvel Pharmaceuticals Limited
1. Study Identification
Unique Protocol Identification Number
NCT04053270
Brief Title
Multicentre Phase III Erythropoietic Protoporphyria Study
Official Title
A Phase III, Multicentre, Randomised, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Subcutanenous Bioresorbable CUV1647 Implants in Patients With Erythropoietic Protoporphyria (EPP)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
May 2007 (Actual)
Primary Completion Date
December 9, 2009 (Actual)
Study Completion Date
December 9, 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Clinuvel Pharmaceuticals Limited
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Erythropoietic Protoporphyria
Keywords
Erythropoietic Protoporphyria, EPP, Afamelanotide
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A
Arm Type
Experimental
Arm Description
Group A was administered active implants on Days 0, 120, 240 and placebo implants on Days 60, 180, 300
Arm Title
Group B
Arm Type
Placebo Comparator
Arm Description
Group B was administered placebo implants on Days 0, 120, 240 and active implants on Days 60, 180, 300
Intervention Type
Drug
Intervention Name(s)
Afamelanotide
Intervention Description
16mg subcutaneous implant
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo subcutaneous implant
Primary Outcome Measure Information:
Title
Cumulative Number of Days of Phototoxic Reactions (Study Efficacy Population)
Description
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
Title
The Mean Number of Phototoxic Reactions (Study Efficacy Population)
Description
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
Secondary Outcome Measure Information:
Title
Cumulative Number of Days With Sunlight Exposure (Study Efficacy Population)
Description
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
Title
Skin Melanin Density (Study Completers Population)
Description
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
Title
Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population
Description
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
Title
Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Head of Clinical Development
Organizational Affiliation
CLINUVEL PHARMACEUTICALS LTD
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
9521433
Citation
Dwyer T, Muller HK, Blizzard L, Ashbolt R, Phillips G. The use of spectrophotometry to estimate melanin density in Caucasians. Cancer Epidemiol Biomarkers Prev. 1998 Mar;7(3):203-6.
Results Reference
result
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Multicentre Phase III Erythropoietic Protoporphyria Study
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