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Phase III Confirmatory Study in Erythropoietic Protoporphyria

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Clinuvel Pharmaceuticals Limited
ClinicalTrials.gov Identifier:
NCT01605136
First received: May 22, 2012
Last updated: March 21, 2013
Last verified: March 2013
History of Changes
  Purpose

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 Intervention Phase
Erythropoietic Protoporphyria
 Drug: Afamelanotide
Drug: Placebo
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Clinuvel Pharmaceuticals Limited:

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). [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Combined sun exposure and phototoxic pain [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Duration of 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).

  • Sun exposure [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Duration of direct sunlight exposure between 10:00 and 18:00 hours during the study.

  • Quality of life [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Assessed by the DLQI and EPP-QoL measured at baseline and on Days 60, 120 and 180.

  • Photoprovocation [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    A subset of patients will be photoprovoked on the lower back and dorsal surface of the hand to determine the minimum symptom dose on Days 0, 30, 60, 90 and 120.

  • Phototoxicity - phototoxic pain [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    The maximum and total pain severity scores (Likert scale) for phototoxic episodes.

    The number of phototoxic episodes reported from Day 0 to Day 180.


  • Safety and Tolerability Endpoints [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Treatment-emergent adverse events (coded as MedDRA Preferred Terms). Changes in hematology, serum chemistry, urinalysis, physical examination and vital sign measurements from Screening to Study Days 60, 120, 180, and at Early Termination Visit, if applicable.


Enrollment: 93
Study Start Date: May 2012
Estimated Study Completion Date: April 2013
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Afamelanotide Drug: Afamelanotide
One 16mg subcutaneous implant every 2 months for 6 months.
Placebo Comparator: Placebo Drug: Placebo
One placebo subcutaneous implant every 2 months for 6 months

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 not yet available on the market.

The purpose of this study is to look at whether afamelanotide can reduce the number and severity of EPP symptoms 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01605136

Locations
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
Principal Investigator: Robert Desnick, MD Mt. Sinai Medical Center
  More Information

No publications provided

Responsible Party: Clinuvel Pharmaceuticals Limited
ClinicalTrials.gov Identifier: NCT01605136     History of Changes
Other Study ID Numbers: CUV039
Study First Received: May 22, 2012
Last Updated: March 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Clinuvel Pharmaceuticals Limited:
Erythropoietic Protoporphyria
EPP
Afamelanotide

Additional relevant MeSH terms:
Protoporphyria, Erythropoietic
Porphyrias, Hepatic
Liver Diseases
Digestive System Diseases
Porphyrias
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Skin Diseases, Genetic
 Skin Diseases
Skin Diseases, Metabolic
Metabolic Diseases
Alpha-MSH
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013