Multicentre Phase III Erythropoietic Protoporphyria Study

NCT04053270 | Completed Phase 3 Results DMC

• 1 other identifier: CUV017
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

This was a phase III, multicentre, randomised, double-blind, placebo-controlled study, to evaluate the safety and efficacy of subcutaneous bioresorbable afamelanotide implants in patients with Erythropoietic Protoporphyria (EPP). The study was conducted with two parallel study arms with crossover between treatments every 60 days. Eligible patients were randomised to a treatment group, and received implants of active treatment (afamelanotide 16mg) or placebo, in an alternating crossover fashion according to the following dosing regime:

• Group A was administered active implants on Days 0, 120, 240 and placebo implants on Days 60, 180, 300
• Group B was administered placebo implants on Days 0, 120, 240 and active implants on Days 60, 180, 300

Conditions

Erythropoietic Protoporphyria

Keywords

Erythropoietic Protoporphyria; EPP; Afamelanotide

Outcome Measures

Primary Outcomes (2)

• Cumulative Number of Days of Phototoxic Reactions (Study Efficacy Population)

  The cumulative number of days where a phototoxic reaction occurred was recorded in the patient diary. The reported data represent a cumulative total for days of phototoxic reactions. 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 primary analysis population for efficacy was revised, to analyze only participants who reported cumulative total Likert pain scores of at least 26 during the study (0-360 days). This population, which was comprised of 60 patients, is identified as the Efficacy population. Participants with less than 26 Likert pain scores were not included in the analysis.

  0-360 days or Early Termination

• The Mean Number of Phototoxic Reactions (Study Efficacy Population)

  The mean number of phototoxic reactions that occurred whilst patients were on active compared with placebo implants. 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 primary analysis population for efficacy was revised, to analyze only participants who reported a cumulative total Likert pain score of at least 26 during the study (0-360 days). This population, which was comprised of 60 patients, is identified as the Efficacy population. Participants with less than 26 Likert pain scores were not included in the analysis.

  0-360 days or Early Termination

Secondary Outcomes (4)

• Cumulative Number of Days With Sunlight Exposure (Study Efficacy Population)

  0-360 days or Early Termination

• Skin Melanin Density (Study Completers Population)

  Day0, Day14, Day30, Day60, Day74, Day90, Day120, Day150, Day180, Day210, Day240, Day270, Day300, Day330, Day360 or Early Termination

• Change in Quality of Life Using SF36 Questionnaire (Physical Component Score) for Study Completers Population

  Day0, Day60, Day120, Day180, Day240, Day300, Day360 or Early Termination

• Change in Quality of Life Using SF36 Questionnaire (Mental Component Score) for Study Completers Population

  Day0, Day60, Day120, Day180, Day240, Day300, Day360 or Early Termination

Study Arms (2)

Group A

EXPERIMENTAL

Group A was administered active implants on Days 0, 120, 240 and placebo implants on Days 60, 180, 300

Drug: Afamelanotide; Drug: Placebo

Group B

PLACEBO COMPARATOR

Group B was administered placebo implants on Days 0, 120, 240 and active implants on Days 60, 180, 300

Drug: Afamelanotide; Drug: Placebo

Interventions

Afamelanotide DRUG

16mg subcutaneous implant

Group A; Group B

Placebo DRUG

Placebo subcutaneous implant

Group A; Group B

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients 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.
• Written informed consent prior to the performance of any study-specific procedure.

You may not qualify if:

• Any allergy to afamelanotide or the polymer contained in the implant or to lignocaine or other local anaesthetic 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.
• Diagnosed with HIV/AIDS or hepatitis.
• 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).
• History of disorders of the gastrointestinal, hepatic, renal, cardiovascular, respiratory, endocrine (including diabetes, Cushing's syndrome, Addison's disease, Peutz-Jeagher syndrome), neurological (including seizures), haematological (especially anaemia of less than 10 g/100 mL) or systemic disease judged to be clinically significant by the Investigator.
• Major medical or psychiatric illness
• 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 was 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).
• Participation in a clinical trial of an investigational agent within 30 days prior to the screening visit.
• Use of regular medications as specified in protocol Section 5.4 Prior and Concomitant Therapy.

Sponsors & Collaborators

• Clinuvel Pharmaceuticals Limited: lead

Related Publications (1)

• Dwyer T, Muller HK, Blizzard L, Ashbolt R, Phillips G. The use of spectrophotometry to estimate melanin density in Caucasians. Cancer Epidemiol Biomarkers Prev. 1998 Mar;7(3):203-6.

  PMID: 9521433 RESULT

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 PHARMACEUTICAL LIMITED

mail@clinuvel.com

+ 61 3 9660 4900

Study Officials

• Head of Clinical Development

  CLINUVEL PHARMACEUTICALS LTD

  STUDY DIRECTOR

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: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2019
• First Posted: August 12, 2019
• Study Start: May 1, 2007
• Primary Completion: December 9, 2009
• Study Completion: December 9, 2009
• Last Updated: October 10, 2019
• Results First Posted: October 10, 2019

Record last verified: 2019-10