Phase III Confirmatory Study in Erythropoietic Protoporphyria

NCT01605136 | Completed Phase 3 Results DMC

• 1 other identifier: CUV039
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 7

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.

Conditions

Erythropoietic Protoporphyria

Keywords

Erythropoietic Protoporphyria; EPP; Afamelanotide

Outcome Measures

Primary Outcomes (1)

• 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.

  Daily for 6 months

Secondary Outcomes (6)

• Combined Sun Exposure and Phototoxic Pain

  Daily for 6 months

• Sun Exposure

  Daily for 6 months

• Quality of Life Score

  Day 60, Day 120, and Day 180 or early termination.

• Photoprovocation

  Day 0, Day 30, Day 60, Day 90 and Day 120.

• Maximum Severity of Phototoxic Reaction Experienced by Participants

  Daily for 6 months

Study Arms (2)

Afamelanotide

EXPERIMENTAL

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

Drug: Afamelanotide

Placebo

PLACEBO COMPARATOR

One placebo subcutaneous implant every 2 months for 6 months.

Drug: Placebo

Interventions

Afamelanotide DRUG

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

Afamelanotide

Placebo DRUG

One placebo subcutaneous implant every 2 months for 6 months

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 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).

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 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).

Sponsors & Collaborators

• Clinuvel Pharmaceuticals Limited: lead

Study Sites (7)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Henry Ford Medical Center

Detroit, Michigan, 48202, 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, 84112, United States

Location

Related Publications (1)

• 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.

  PMID: 26132941 DERIVED

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
• Organization: Clinuvel Inc.

Dennis.Wright@clinuvel.com

646 527 7310

Study Officials

• Robert Desnick, MD

  Mt. Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: May 22, 2012
• First Posted: May 24, 2012
• Study Start: May 1, 2012
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: September 19, 2019
• Results First Posted: August 26, 2019

Record last verified: 2019-09

Locations

US (7)