Phase II Confirmatory Study in Erythropoietic Protoporphyria (EPP)

NCT01097044 | Completed Phase 2 Results DMC

• 1 other identifier: CUV030
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 6

Brief Summary

This is a randomized placebo-controlled study to be conducted in two parallel study arms for a six month period (three doses). Approximately 10 eligible patients per center will be enrolled and 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 To determine eligibility for study inclusion, patients will undergo a screening evaluation 7 to 14 days prior to the administration of the first dose. The number and severity of phototoxic reactions will be determined Days 60, 120, and 180. Quality of life will be measured using the EPP specific questionnaire (EPP-QoL) every 60 days and the DLQI questionnaire every 7 days, beginning at Day 0 until Day 180. Participants will visit the clinic on Days 60, 120 and 180 for assessments of adverse events.

Conditions

Erythropoietic Protoporphyria

Keywords

Erythropoietic Protoporphyria; EPP; Afamelanotide

Outcome Measures

Primary Outcomes (1)

• Time in Direct Sunlight Between 10:00-15:00 on Pain-free Days

  The amount of direct sunlight exposure between 10:00 and 15:00 hours on days when no pain was experienced (e.g. 11-point Likert pain score of 0). Time was recorded in a patient dairy 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.

  Daily for 6 months

Secondary Outcomes (6)

• Maximum Severity of Phototoxic Reaction Experienced by Participants

  Daily for 6 months

• Quality of Life Measured by Participant Completed Questionnaire

  Day 0, Day 60, Day 120, Day 180

• Change of Total Protoporphyrin IX Level in Participants

  Baseline, Day 60, Day 120, Day 180

• Number of Participants With Phototoxic Reactions With Likert Severity Scores ≥ 4 and ≥ 7

  Daily for 6 months

• Number of Phototoxic Reactions Experienced by Participants

  Daily for 6 months

Study Arms (2)

Afamelanotide

EXPERIMENTAL

Dose: 16 mg implant; release of 16 mg over 7 to 10 days Mode of administration: Subcutaneous implantation Frequency: Every 60 days (on Days 0, 60 and 120)

Drug: Afamelanotide

Placebo

PLACEBO COMPARATOR

Dose: 16 mg implant; Mode of administration: Subcutaneous implantation Frequency: Every 60 days (on Days 0, 60 and 120)

Drug: Placebo

Interventions

Afamelanotide DRUG

One 16mg subcutaneous implant every 2 months for 6 months. (3 implants in total)

Afamelanotide

Placebo DRUG

One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total)

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects with characteristic photosensitivity of EPP symptoms and positive diagnosis of EPP confirmed by laboratory result of elevated total protoporphyrin IX.
• 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).

You may not qualify if:

• 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 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 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 within 60 days prior to the screening visit.
• 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).

Sponsors & Collaborators

• Clinuvel Pharmaceuticals Limited: lead

Study Sites (6)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Mt. Sinai

New York, New York, 10029, United States

Location

Carolina's Medical Center Cannon Research

Charlotte, North Carolina, 29203, United States

Location

University of Texas

Galveston, Texas, 77555, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Conditions

Protoporphyria, Erythropoietic

Interventions

afamelanotide

Condition Hierarchy (Ancestors)

Porphyrias, Hepatic; Liver Diseases; Digestive System Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases; Skin and Connective Tissue Diseases; Porphyrias; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Dr. Dennis Wright, Acting Chief Scientific Officer
• Organization: Clinuvel Pharmaceuticals Limited

Dennis.Wright@clinuvel.com

646 527 7310

Study Officials

• Robert Desnick, MD

  Mt. Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2010
• First Posted: April 1, 2010
• Study Start: April 1, 2010
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: October 28, 2019
• Results First Posted: September 17, 2019

Record last verified: 2019-10

Locations

US (6)