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Phase III Confirmatory Study in Erythropoietic Protoporphyria

Primary Purpose

Erythropoietic Protoporphyria

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Afamelanotide
Placebo
Sponsored by
Clinuvel Pharmaceuticals Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Erythropoietic Protoporphyria focused on measuring Erythropoietic Protoporphyria, EPP, Afamelanotide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female subjects with characteristic symptoms of EPP phototoxicity and a biochemically-confirmed diagnosis of EPP.
  • 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).

Exclusion Criteria:

  • 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 polymorphic light eruption, actinic prurigo, discoid lupus erythematosus, chronic actinic dermatitis or solar urticaria.
  • 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 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.
  • 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).

Sites / Locations

  • University of Alabama
  • University of California, San Francisco
  • Henry Ford Medical Center
  • Mt. Sinai
  • Carolina's Medical Center Cannon Research
  • University of Texas
  • University of Utah

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Afamelanotide

Placebo

Arm Description

One 16mg subcutaneous implant every 2 months for 6 months.

One placebo subcutaneous implant every 2 months for 6 months.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Sun Exposure
Duration of direct sunlight exposure between 10:00 and 18:00 hours during the study.
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).
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.
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.
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.

Full Information

First Posted
May 22, 2012
Last Updated
September 6, 2019
Sponsor
Clinuvel Pharmaceuticals Limited
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1. Study Identification

Unique Protocol Identification Number
NCT01605136
Brief Title
Phase III Confirmatory Study in Erythropoietic Protoporphyria
Official Title
A Phase III, Multicentre, Double-Blind, Randomized, Placebo-Controlled Study to Confirm the Safety and Efficacy of Subcutaneous Bioresorbable Afamelanotide Implants in Patients With Erythropoietic Protoporphyria (EPP)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
July 2013 (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 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: 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 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.
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) 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.

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
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
93 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Afamelanotide
Arm Type
Experimental
Arm Description
One 16mg subcutaneous implant every 2 months for 6 months.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
One placebo subcutaneous implant every 2 months for 6 months.
Intervention Type
Drug
Intervention Name(s)
Afamelanotide
Intervention Description
One 16mg subcutaneous implant every 2 months for 6 months.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
One placebo subcutaneous implant every 2 months for 6 months
Primary Outcome Measure Information:
Title
Duration of Direct Sunlight Exposure Between 10:00 and 18:00 Hours on Days When no Pain Was Experienced (Pain Score of 0).
Description
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.
Time Frame
Daily for 6 months
Secondary Outcome Measure Information:
Title
Combined Sun Exposure and Phototoxic Pain
Description
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.
Time Frame
Daily for 6 months
Title
Sun Exposure
Description
Duration of direct sunlight exposure between 10:00 and 18:00 hours during the study.
Time Frame
Daily for 6 months
Title
Quality of Life Score
Description
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).
Time Frame
Day 60, Day 120, and Day 180 or early termination.
Title
Photoprovocation
Description
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.
Time Frame
Day 0, Day 30, Day 60, Day 90 and Day 120.
Title
Maximum Severity of Phototoxic Reaction Experienced by Participants
Description
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.
Time Frame
Daily for 6 months
Title
Total Number Phototoxic Reactions Experienced by Participants
Description
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.
Time Frame
Daily for 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female subjects with characteristic symptoms of EPP phototoxicity and a biochemically-confirmed diagnosis of EPP. 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). Exclusion Criteria: 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 polymorphic light eruption, actinic prurigo, discoid lupus erythematosus, chronic actinic dermatitis or solar urticaria. 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 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. 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Desnick, MD
Organizational Affiliation
Mt. Sinai Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Henry Ford Medical Center
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Mt. Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Carolina's Medical Center Cannon Research
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
29203
Country
United States
Facility Name
University of Texas
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26132941
Citation
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.
Results Reference
derived

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Phase III Confirmatory Study in Erythropoietic Protoporphyria

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