Afamelanotide as Adjunctive Therapy in Patients Undergoing Photodynamic Therapy (PDT) Utilising Porfimer Sodium

• Sponsor: Clinuvel Pharmaceuticals Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04425746
• Collaborator: (none)

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate the safety and efficacy of afamelanotide (previously developed as CUV1647) as adjunctive therapy in patients undergoing photodynamic therapy using porfimer sodium.

Condition or Disease	Intervention/Treatment	Phase
Patients Undergoing Photodynamic Therapy Using Porfimer Sodium	Drug: Afamelanotide; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II, Multicentre, Double-blind, Placebo Controlled, Pilot Study to Evaluate the Safety and Efficacy of CUV1647 (Afamelanotide) as Adjunctive Therapy in Patients Undergoing Photodynamic Therapy (PDT) Utilising Porfimer Sodium
• Actual Study Start Date: Aug 5, 2008
• Actual Primary Completion Date: May 28, 2009
• Actual Study Completion Date: May 28, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Afamelanotide Subjects visited the clinic on Day 0 (administration of afamelanotide implant and porfimer sodium), Day 2 (photodynamic therapy), and Days 20 and 90 for assessments of adverse events, concomitant medication and the results of evaluation of phototoxicity.	Drug: Afamelanotide
Placebo Comparator: Placebo Subjects visited the clinic on Day 0 (administration of placebo implant and porfimer sodium), Day 2 (photodynamic therapy), and Days 20 and 90 for assessments of adverse events, concomitant medication and the results of evaluation of phototoxicity.	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. The First Day on Which Patients Are Free From Symptoms of Phototoxicity Following Phototesting [From Day 04 to Day 90]

Secondary Outcome Measures

1. Change in Quality of Life [From Day 0 to Day 20, Day 60 and Day 90]

   Quality of life, as measured by the Short Form-36 Health survey (SF-36) (quality of life questionnaire). The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female Caucasian subjects undergoing photodynamic therapy with porfimer sodium;

• Aged greater than 18 years;

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

Exclusion Criteria:

• Known allergy or hypersensitivity to afamelanotide or the polymer contained in the implant;

• Non-Caucasian patients;

• 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;

• 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);

• Participation in a simultaneous clinical trial for another investigational agent or within 30 days prior to the screening visit;

• Patients unable to give informed consent;

• Patient needs for concomitant medication with potential photosensitizing effects e.g. antibiotics like tetracyclines.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Clinuvel Pharmaceuticals Limited

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Clinuvel Pharmaceuticals Limited
• ClinicalTrials.gov Identifier: NCT04425746
• Other Study ID Numbers: CUV025
• First Posted: Jun 11, 2020
• Last Update Posted: Oct 1, 2021
• Last Verified: Sep 1, 2021

• Additional relevant MeSH terms: Afamelanotide

Study Results

Participant Flow

Arm/Group Title	Afamelanotide	Placebo
Arm/Group Description	Subjects visited the clinic on Day 0 (administration of afamelanotide implant and porfimer sodium), Day 2 (photodynamic therapy), and Days 20 and 90 for assessments of adverse events, concomitant medication, and the results of evaluation of phototoxicity.	Subjects visited the clinic on Day 0 (administration of placebo implant and porfimer sodium), Day 2 (photodynamic therapy), and Days 20 and 90 for assessments of adverse events, concomitant medication and the results of evaluation of phototoxicity.
Period Title: Overall Study
STARTED	9	7
COMPLETED	9	6
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Afamelanotide	Placebo	Total
Arm/Group Description	Subjects visited the clinic on Day 0 (administration of afamelanotide implant and porfimer sodium), Day 2 (photodynamic therapy), and Days 20 and 90 for assessments of adverse events, concomitant medication, and the results of evaluation of phototoxicity.	Subjects visited the clinic on Day 0 (administration of placebo implant and porfimer sodium), Day 2 (photodynamic therapy), and Days 20 and 90 for assessments of adverse events, concomitant medication and the results of evaluation of phototoxicity.	Total of all reporting groups
Overall Participants	9	7	16
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	63.0 (9.3)	72.6 (8.8)	67.2 (10.0)
Sex: Female, Male (Count of Participants)
Female	0 0%	1 14.3%	1 6.3%
Male	9 100%	6 85.7%	15 93.8%

Outcome Measures

1. Primary Outcome

Title	The First Day on Which Patients Are Free From Symptoms of Phototoxicity Following Phototesting
Time Frame	From Day 04 to Day 90

Outcome Measure Data

Analysis Population Description

The planned primary efficacy endpoint was the number of days for patients to be free of phototoxic reactions following phototesting. This was recorded by patients through diaries, however these diaries were not completed appropriately, thus data could not be collected. Thus, the efficacy analysis was performed using the secondary efficacy endpoint, change in quality of life as measured by SF-36.

Arm/Group Title	Afamelanotide	Placebo
Arm/Group Description	Subjects visited the clinic on Day 0 (administration of afamelanotide implant and porfimer sodium), Day 2 (photodynamic therapy), and Days 20 and 90 for assessments of adverse events, concomitant medication and the results of evaluation of phototoxicity. Afamelanotide	Subjects visited the clinic on Day 0 (administration of placebo implant and porfimer sodium), Day 2 (photodynamic therapy), and Days 20 and 90 for assessments of adverse events, concomitant medication and the results of evaluation of phototoxicity. Placebo
Measure Participants	0	0

2. Secondary Outcome

Title	Change in Quality of Life
Description	Quality of life, as measured by the Short Form-36 Health survey (SF-36) (quality of life questionnaire). The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability.
Time Frame	From Day 0 to Day 20, Day 60 and Day 90

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Afamelanotide	Placebo
Arm/Group Description	Subjects visited the clinic on Day 0 (administration of afamelanotide implant and porfimer sodium), Day 2 (photodynamic therapy), and Days 20 and 90 for assessments of adverse events, concomitant medication, and the results of evaluation of phototoxicity.	Subjects visited the clinic on Day 0 (administration of placebo implant and porfimer sodium), Day 2 (photodynamic therapy), and Days 20 and 90 for assessments of adverse events, concomitant medication and the results of evaluation of phototoxicity.
Measure Participants	7	5
Day 20 - Day 0 (Physical functioning)	-5.7	8.0
Day 20 - Day 0 (Role Physical)	-14.6	0.0
Day 20 - Day 0 (Bodily Pain)	-1.4	-11.6
Day 20 - Day 0 (General Health)	2.0	-27.6
Day 20 - Day 0 (Vitality)	-1.5	-7.9
Day 20 - Day 0 (Social functioning)	1.2	7.5
Day 20 - Day 0 (Role - Emotional)	-7.1	10.0
Day 20 - Day 0 (Mental Health)	1.9	3.0
Day 20 - Day 0 (Physical Component Summary)	-2.6	-4.8
Day 20 - Day 0 (Mental Component Summary)	0.3	2.7
Day 60 - Day 0 (Physical Functioning)	-13.6	-10.0
Day 60 - Day 0 (Role- Physical)	-8.9	-13.8
Day 60 - Day 0 (Bodily Pain)	2.0	-21.4
Day 60 - Day 0 (General Health)	-4.2	-33.0
Day 60 - Day 0 (Vitality)	5.4	-5.4
Day 60 - Day 0 (Social Functioning)	0.0	-17.5
Day 60 - Day 0 (Role- Emotional)	6.0	-10.0
Day 60 - Day 0 (Mental Health)	2.9	-2.0
Day 60 - Day 0 (Physical Component Summary)	-4.7	-9.4
Day 60 - Day 0 (Mental Component Summary)	4.3	-2.5
Day 90 - Day 0 (Physical Functioning)	-13.6	-5.0
Day 90 - Day 0 (Role- Physical)	0.0	-3.8
Day 90 - Day 0 (Bodily pain)	-2.7	-13.8
Day 90 - Day 0 (General Health)	-4.1	-32.0
Day 90 - Day 0 (Social Functioning)	0.0	-12.5
Day 90 - Day 0 (Role- Emotional)	0.0	-11.7
Day 90 - Day 0 (Mental Health)	-2.1	-9.0
Day 90 - Day 0 (Physical Component Summary)	-3.0	-5.1
Day 90 - Day 0 (Mental Component Summary)	0.7	-6.3

Adverse Events

Adverse Event Reporting Description	None of the serious adverse events were deemed to be related to study drug
Arm/Group Title	Afamelanotide		Placebo
Arm/Group Description	Subjects visited the clinic on Day 0 (administration of afamelanotide implant and porfimer sodium), Day 2 (photodynamic therapy), and Days 20 and 90 for assessments of adverse events, concomitant medication and the results of evaluation of phototoxicity. Afamelanotide		Subjects visited the clinic on Day 0 (administration of placebo implant and porfimer sodium), Day 2 (photodynamic therapy), and Days 20 and 90 for assessments of adverse events, concomitant medication and the results of evaluation of phototoxicity. Placebo
All Cause Mortality
	Afamelanotide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Afamelanotide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/9 (22.2%)		3/7 (42.9%)
Gastrointestinal disorders
Haematemesis	0/9 (0%)		1/7 (14.3%)
Oesophageal stenosis	1/9 (11.1%)		0/7 (0%)
Infections and infestations
Subdiaphragmatic abscess	0/9 (0%)		1/7 (14.3%)
Injury, poisoning and procedural complications
Overdose of Previscan (Fluindione)	1/9 (11.1%)		0/7 (0%)
Drug toxicity (morphine)	1/9 (11.1%)		0/7 (0%)
Vascular disorders
Thrombosis	0/9 (0%)		1/7 (14.3%)
Other (Not Including Serious) Adverse Events
	Afamelanotide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/9 (66.7%)		1/7 (14.3%)
Gastrointestinal disorders
Dyspepsia	1/9 (11.1%)		0/7 (0%)
Nausea	2/9 (22.2%)		0/7 (0%)
Nervous system disorders
Headache	3/9 (33.3%)		0/7 (0%)
Skin and subcutaneous tissue disorders
Erythema	1/9 (11.1%)		1/7 (14.3%)

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.