Phase III Confirmatory Study in Erythropoietic Protoporphyria (EPP)

• Sponsor: Clinuvel Pharmaceuticals Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00979745
• Collaborator: (none)
• Enrollment: 74
• Locations: 8
• Arms: 2
• Duration (Months): 19.9
• Patients Per Site: 9.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Afamelanotide is a man-made drug being studied for use as a preventative medication for 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 (approximately 2 cm x 0.15 cm) to be administered under the skin. The implant may contain the study drug afamelanotide or a placebo (inactive medication).

Over 450 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. Once inserted, the implant will remain in the body after afamelanotide has been released and will slowly dissolve.

This study will help to provide more information about afamelanotide. This information will be used to determine the safety and efficacy (the ability of the drug to produce an effect) of this drug in EPP sufferers.

Up to 70 people will participate in this study from study sites across Europe.

Condition or Disease	Intervention/Treatment	Phase
Erythropoietic Protoporphyria	Drug: Afamelanotide; Drug: Placebo	Phase 3

Detailed Description

PURPOSE:

To determine whether afamelanotide can reduce the severity of phototoxic reactions in patients with EPP.

THEORETICAL FRAMEWORK:

EPP is a genetic photosensitivity disorder where the mainstays of management are covering up from sunlight, systemic beta carotene and the use of controlled courses of UVR treatment. One of the mechanisms for the protective effects of UVR treatment is the increase in melanin content of the skin. UVR treatment causes DNA damage to skin cells and increases the risk for skin cancers, hence it is unwise for this to be used on a recurring basis. Afamelanotide, through its ability to stimulate melanin production without causing the DNA damage associated with UVR treatment, appears to be a promising agent to combat this distressing disorder.

STUDY DESIGN:

This is a phase III, randomised, placebo controlled study to evaluate the safety and efficacy of subcutaneous implants of afamelanotide in patients suffering from EPP. The study will be performed in compliance with Good Clinical Practice (GCP) including the archiving of essential documents.

METHODOLOGY:

The target population consists of male and female participants. Up to 70 patients with diagnosed EPP (from past case history) and fulfilling the necessary inclusion/exclusion criteria will be enrolled. Potential study patients will be identified from each centre's records of patients with well characterised history (or documented diagnosis) of EPP.

Patients will be enrolled and will receive afamelanotide (16 mg implants) or placebo according to the following dosing regime:

• Group A will be administered active implants on Days 0, 60, 120, 180 and 240.

• Group B will be administered placebo implants on Days 0, 60, 120, 180 and 240.

Study Design

• Study Type: Interventional
• Actual Enrollment: 74 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Phase III, Multicentre, Double-Blind, Randomised, Placebo-Controlled Study to Confirm the Safety and Efficacy of Subcutaneous Bioresorbable Afamelanotide Implants in Patients With Erythropoietic Protoporphyria (EPP)
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Afamelanotide	Drug: Afamelanotide; One 16mg subcutaneous implant every 2 months for 9 months.; Other Names: CUV1647
Placebo Comparator: Placebo	Drug: Placebo; One 16mg subcutaneous implant every 2 months for 9 months.

Outcome Measures

Primary Outcome Measures

1. The Duration of Direct Sunlight Exposure Between 10:00 and 15:00 Hours on Days When Patients Did Not Report Phototoxicity-related Pain (Likert Pain Scale Score of 0) [From baseline to Day 270]

Secondary Outcome Measures

1. Number of Phototoxic Reactions [9 months]

2. Quality of Life Measured by Patient Completed Questionnaire [9 months]

3. Free Protoporphyrin IX Level [9 months]

4. Treatment Emergent Adverse Events [9 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female subjects 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 (inclusive)

• Written informed consent prior to the performance of any study-specific procedures.

Exclusion Criteria:

• Any allergy to afamelanotide or the polymer contained in the implant or to lignocaine or other local anaesthetic to be 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.

• 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).

• 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 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).

• Sexually active men with partners of child bearing potential not using barrier contraception during the trial and for a period of three months thereafter.

• Participation in a clinical trial of 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HUS:n Iho-ja allergiasairaala (Skin and Allergy Hospital)	Helsinki		Finland
2	Centre Français des Porphyries, Hôpital Louis Mourier	Colombes	Cedex	France	92701
3	Department of Dermatology , Heinrich-Heine-University Duesseldorf	Duesseldorf		Germany	40225
4	Beaumont Hospital, Department of Dermatology	Dublin		Ireland	9
5	Academisch Ziekenhuis Maastricht	Maastricht		Netherlands
6	Erasmus Medical Center	Rotterdam		Netherlands
7	St Woolos Hospital	Newport	Wales	United Kingdom
8	Photobiology Unit - Hope Hospital, University of Manchester	Manchester		United Kingdom	M6 8HD

Sponsors and Collaborators

• Clinuvel Pharmaceuticals Limited

Investigators

• Principal Investigator: Alex Anstey, MBBS, FRCP, St Woolos Hospital, Newport
• Principal Investigator: Jorge Frank, MD, PhD, Academisch Ziekenhuis Maastricht
• Principal Investigator: Raili Kauppinen, MD, PhD, University Central Hospital of Helsinki
• Principal Investigator: Eric JG Sijbrands, MD, PhD, Erasmus Medical Center
• Principal Investigator: Jean-Charles Deybach, MD. PhD, Centre Francais des Porphyries, Hopital Louis Mourier, Colombes, France
• Principal Investigator: Sandra Hanneken, MD, Heinrich-Heine Universität, Düsseldorf, Germany
• Principal Investigator: Gillian M Murphy, MD PhD, Beaumont Hospital, Dublin, Ireland
• Principal Investigator: Lesley E Rhodes, MD PhD, Hope Hospital, University of Manchester, UK

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Clinuvel Pharmaceuticals Limited
• ClinicalTrials.gov Identifier: NCT00979745
• Other Study ID Numbers: CUV029
• First Posted: Sep 18, 2009
• Last Update Posted: Oct 12, 2021
• Last Verified: Sep 1, 2021

• Keywords provided by Clinuvel Pharmaceuticals Limited: Erythropoietic Protoporphyria; EPP; Afamelanotide
• Additional relevant MeSH terms: Protoporphyria, Erythropoietic; Afamelanotide

Study Results

Participant Flow

Arm/Group Title	Experimental: Afamelanotide	Placebo
Arm/Group Description	administered afamelanotide implants on Days 0, 60, 120, 180 and 240.	administered placebo implants on Days 0, 60, 120, 180 and 240.
Period Title: Overall Study
STARTED	38	36
COMPLETED	34	34
NOT COMPLETED	4	2

Baseline Characteristics

Arm/Group Title	Experimental: Afamelanotide	Placebo	Total
Arm/Group Description	administered afamelanotide implants on Days 0, 60, 120, 180 and 240.	administered placebo implants on Days 0, 60, 120, 180 and 240.	Total of all reporting groups
Overall Participants	38	36	74
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.3 (13)	38.6 (11.6)	38.45 (12.3)
Sex: Female, Male (Count of Participants)
Female	21 55.3%	16 44.4%	37 50%
Male	17 44.7%	20 55.6%	37 50%

Outcome Measures

1. Primary Outcome

Title	The Duration of Direct Sunlight Exposure Between 10:00 and 15:00 Hours on Days When Patients Did Not Report Phototoxicity-related Pain (Likert Pain Scale Score of 0)
Time Frame	From baseline to Day 270

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental: Afamelanotide	Placebo
Arm/Group Description	administered afamelanotide implants on Days 0, 60, 120, 180 and 240.	administered placebo implants on Days 0, 60, 120, 180 and 240.
Measure Participants	38	36
Median (Full Range) [Hours]	6.0	0.75

2. Secondary Outcome

Title	Number of Phototoxic Reactions
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Quality of Life Measured by Patient Completed Questionnaire
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Free Protoporphyrin IX Level
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Treatment Emergent Adverse Events
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Experimental: Afamelanotide		Placebo
Arm/Group Description	Afamelanotide implants administered on Days 0, 60, 120, 180 and 240.		Placebo implants administered on Days 0, 60, 120, 180 and 240.
All Cause Mortality
	Experimental: Afamelanotide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Experimental: Afamelanotide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/36 (0%)
Other (Not Including Serious) Adverse Events
	Experimental: Afamelanotide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/38 (42.1%)		12/36 (33.3%)
Gastrointestinal disorders
Abdominal pain	2/38 (5.3%)		0/36 (0%)
Nausea	6/38 (15.8%)		3/36 (8.3%)
General disorders
Implant site discolouration	4/38 (10.5%)		0/36 (0%)
Investigations
Blood urine present	2/38 (5.3%)		2/36 (5.6%)
Gamma-glutamyltransferase increased	0/38 (0%)		3/36 (8.3%)
Nervous system disorders
Headache	7/38 (18.4%)		7/36 (19.4%)
Pregnancy, puerperium and perinatal conditions
Dizziness	2/38 (5.3%)		0/36 (0%)
Skin and subcutaneous tissue disorders
Pigmentation disorder	3/38 (7.9%)		0/36 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.