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Phase III Confirmatory Study in Erythropoietic Protoporphyria

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ClinicalTrials.gov Identifier: NCT01605136
Recruitment Status : Completed
First Posted : May 24, 2012
Results First Posted : August 26, 2019
Last Update Posted : September 9, 2019
Sponsor:
Information provided by (Responsible Party):
Clinuvel Pharmaceuticals Limited

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.


Condition or disease Intervention/treatment Phase
Erythropoietic Protoporphyria Drug: Afamelanotide Drug: Placebo Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 93 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : May 2012
Actual Primary Completion Date : July 2013
Actual Study Completion Date : July 2013


Arm Intervention/treatment
Experimental: Afamelanotide
One 16mg subcutaneous implant every 2 months for 6 months.
Drug: Afamelanotide
One 16mg subcutaneous implant every 2 months for 6 months.

Placebo Comparator: Placebo
One placebo subcutaneous implant every 2 months for 6 months.
Drug: Placebo
One placebo subcutaneous implant every 2 months for 6 months




Primary Outcome Measures :
  1. Duration of Direct Sunlight Exposure Between 10:00 and 18:00 Hours on Days When no Pain Was Experienced (Pain Score of 0). [ Time Frame: Daily for 6 months ]

    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 :
  1. Combined Sun Exposure and Phototoxic Pain [ Time Frame: Daily for 6 months ]

    Time in direct sunlight exposure between 10:00 and 18:00 hours on pain free days (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.


  2. Sun Exposure [ Time Frame: Daily for 6 months ]
    Duration of direct sunlight exposure between 10:00 and 18:00 hours during the study.

  3. Quality of Life Score [ Time Frame: Day 60, Day 120, and Day 180 or early termination. ]

    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).


  4. Photoprovocation [ Time Frame: Day 0, Day 30, Day 60, Day 90 and Day 120. ]

    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.


  5. Maximum Severity of Phototoxic Reaction Experienced by Participants [ Time Frame: Daily for 6 months ]

    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.


  6. Total Number Phototoxic Reactions Experienced by Participants [ Time Frame: Daily for 6 months ]

    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.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01605136


Locations
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United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35294
United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Michigan
Henry Ford Medical Center
Detroit, Michigan, United States, 48202
United States, New York
Mt. Sinai
New York, New York, United States, 10029
United States, North Carolina
Carolina's Medical Center Cannon Research
Charlotte, North Carolina, United States, 29203
United States, Texas
University of Texas
Galveston, Texas, United States, 77555
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Clinuvel Pharmaceuticals Limited
Investigators
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Principal Investigator: Robert Desnick, MD Mt. Sinai Medical Center

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Clinuvel Pharmaceuticals Limited
ClinicalTrials.gov Identifier: NCT01605136     History of Changes
Other Study ID Numbers: CUV039
First Posted: May 24, 2012    Key Record Dates
Results First Posted: August 26, 2019
Last Update Posted: September 9, 2019
Last Verified: August 2019
Keywords provided by Clinuvel Pharmaceuticals Limited:
Erythropoietic Protoporphyria
EPP
Afamelanotide
Additional relevant MeSH terms:
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Protoporphyria, Erythropoietic
Porphyrias, Hepatic
Liver Diseases
Digestive System Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Porphyrias
Metabolic Diseases
Afamelanotide
alpha-MSH
Dermatologic Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs