Erythropoietic ProtoporphyriaPhase 3NCT04053270

Multicentre Phase III Erythropoietic Protoporphyria Study

A Phase 3 study testing Afamelanotide in people with Erythropoietic Protoporphyria, run by Clinuvel Pharmaceuticals Limited.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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). Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Erythropoietic Protoporphyria
What is being tested?: Afamelanotide
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 100 participants
Where: No sites listed yet
Study dates: May 2007to 9 Dec 2009
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

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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.
Any factors that may affect skin reflectance measurements.

About this study

Official title: A Phase III, Multicentre, Randomised, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Subcutanenous Bioresorbable CUV1647 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

Read the detailed description

Afamelanotide is a man-made drug being studied for use as a preventative medication for Erythropoietic Protoporphyria (EPP) sufferers. It is a synthetically produced analogue of human alpha melanocyte stimulating hormone (alpha-MSH).

The study will involve the use of an implant, which comes in the form of a small rod to be administered under the skin. The implant may contain the study drug afamelanotide or a placebo (inactive medication).

This study aims to provide insight into the effectiveness of afamelanotide under normal conditions of use in EPP patients.

Conditions: Erythropoietic Protoporphyria
Being tested: Afamelanotide, Placebo
Keywords: Erythropoietic Protoporphyria, EPP, Afamelanotide
Medical subject headings: Protoporphyria, Erythropoietic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AfamelanotideDrug
16mg subcutaneous implant
PlaceboDrug
Placebo subcutaneous implant

Study groups in NCT04053270
Study group	Role	What they receive
Group A	Experimental	Group A was administered active implants on Days 0, 120, 240 and placebo implants on Days 60, 180, 300 Receives: 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 Receives: Drug: Afamelanotide; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 0-360 days or Early Termination

Secondary outcomes (4)

Cumulative Number of Days With Sunlight Exposure (Study Efficacy Population)
The number of days with sunlight exposure was recorded in the patient diary. The sunlight exposures were divided into the following categories: none, < 1 hour, 1 to 3 hours, 3 to 6 hours and > 6 hours per day.
Measured: 0-360 days or Early Termination
Skin Melanin Density (Study Completers Population)
Changes in melanin density (MD) (measured by spectrophotometry) at each visit by group.
Participants had their skin pigmentation measured by a non-invasive quantitative skin chromaticity (reflectance) reading. Reflectance by the skin of light measured at the wavelengths of 400 nm and 420 nm was recorded using a Minolta cm-2500d spectrophotometer at the following skin sites: forehead, left cheek, right inside upper arm, left medial forearm, right side of abdomen (avoiding implant insertion site), left side of sacral region/buttock.
Melanin density was determined for each skin site using the method of Dwyer et al 1998.
Measured: 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
The Summary of SF36 change from Baseline of Physical Component Score (PCS) to the scores during treatment on Days 60, 120, 180, 240, 300 and 360 using the SF36 questionnaire.
The SF-36 (The Short Form 36 Health Survey) consists of eight scaled scores, which are the weighted sums of the questions in each section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight.
The higher scores represent better health-related quality-of-life.
Measured: 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
The Summary of SF36 change from Baseline of Mental Component Score (MCS) to the scores during treatment on Days 60, 120, 180, 240, 300 and 360 using the SF36 questionnaire.
The SF-36 (The Short Form 36 Health Survey) consists of eight scaled scores, which are the weighted sums of the questions in each section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight.
The higher scores represent better health-related quality-of-life.
Measured: Day0, Day60, Day120, Day180, Day240, Day300, Day360 or Early Termination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 20079 Dec 2009

First posted12 Aug 2019
Study startMay 2007
Primary completion9 Dec 2009
Study completion9 Dec 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Erythropoietic ProtoporphyriaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 100 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04053270
Sponsor's protocol ID: CUV017
Status last verified: Oct 2019
First submitted: 8 Aug 2019
Last updated: 10 Oct 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 9521433

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Enrolling by invitationPhase 2/3
HELIOS: Open-Label, Long-Term Extension Study to Investigate the Safety, Tolerability, and Efficacy of DISC-1459 (Bitopertin) in Participants With EPP or XLP
Erythropoietic Protoporphyria
RecruitingPhase 2/3
A Study to Investigate PORT-77 Oral Dosing Compared With Placebo in Participants With Erythropoietic Protoporphyria (EPP) or X-linked Protoporphyria (XLP)
Erythropoietic Protoporphyria (EPP), X-Linked Protoporphyria (XLP)
Active, not recruitingPhase 3
Extension Study to Evaluate Safety and Tolerability of Oral Dersimelagon (MT-7117) in Subjects With Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)
EPP, XLP
RecruitingObservational study
Longitudinal Study of the Porphyrias
Acute Porphyrias, Cutaneous Porphyrias
RecruitingObservational study
Observational Study of Adults and Adolescents With Erythropoietic Protoporphyria (EPP) and X-linked Porphyria (XLP)
Erythropoietic Protoporphyria (EPP), X-Linked Porphyria (XLP)

All Erythropoietic Protoporphyria trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III, Multicentre, Randomised, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Subcutanenous Bioresorbable CUV1647 Implants in Patients With Erythropoietic Protoporphyria (EPP)
ClinicalTrials.gov ID: NCT04053270
Acronym / sponsor ID: CUV017
Conditions: Erythropoietic Protoporphyria
Keywords: Erythropoietic Protoporphyria, EPP, Afamelanotide
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 100 participants (actual)
Lead sponsor: Clinuvel Pharmaceuticals LimitedIndustry (pharma, biotech, devices)
Study start: May 2007 (actual)
Primary completion: 9 Dec 2009 (actual)
Study completion: 9 Dec 2009 (actual)
First posted: 12 Aug 2019 (actual)
Results: Posted 10 Oct 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The study was conducted with two parallel study arms with crossover between treatments every 60 days.

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

Detailed description

This study aims to provide insight into the effectiveness of afamelanotide under normal conditions of use in EPP patients.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Group A	Experimental	Drug: Afamelanotide, Drug: PlaceboGroup A was administered active implants on Days 0, 120, 240 and placebo implants on Days 60, 180, 300
Group B	Placebo comparator	Drug: Afamelanotide, Drug: PlaceboGroup B was administered placebo implants on Days 0, 120, 240 and active implants on Days 60, 180, 300

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (16 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Afamelanotide16mg subcutaneous implant	Drug	Group A, Group B
PlaceboPlacebo subcutaneous implant	Drug	Group A, Group B

Primary outcome

Cumulative Number of Days of Phototoxic Reactions (Study Efficacy Population)
Time frame: 0-360 days or Early Termination
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.
The Mean Number of Phototoxic Reactions (Study Efficacy Population)
Time frame: 0-360 days or Early Termination
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.

4 secondary outcomes

Cumulative Number of Days With Sunlight Exposure (Study Efficacy Population)
Time frame: 0-360 days or Early Termination
Skin Melanin Density (Study Completers Population)
Time frame: 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
Time frame: 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
Time frame: Day0, Day60, Day120, Day180, Day240, Day300, Day360 or Early Termination

Results and safety

Results posted to the registry on 10 Oct 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group A	49	47
Group B	51	46

Primary outcome: Cumulative Number of Days of Phototoxic Reactions (Study Efficacy Population)

Time frame: 0-360 days or Early Termination. Number. Unit: Days

Measure	Afamelanotide n = 60	Placebo n = 60
Severe Pain	39	45
Moderate Pain	129	179
Mild Pain	1126	1237
No Pain	8650	8484

Population analysed: Participants who reported a cumulative total Likert pain score of at least 26 during the study (0-360 days), which was comprised of 60 patients, is identified as the Efficacy population.

Primary outcome: The Mean Number of Phototoxic Reactions (Study Efficacy Population)

Time frame: 0-360 days or Early Termination. Mean (Standard Deviation). Unit: counts of episodes

Measure	Group A n = 32	Group B n = 28
Day 0	1.44 (3.25)	2.64 (5.33)
Day 60	0.56 (1.87)	0.11 (0.31)
Day 120	1.09 (2.08)	0.79 (2.25)
Day 180	0.32 (2.07)	0.78 (0.61)
Day 240	0.63 (1.52)	2.21 (3.57)
Day 300	0.72 (1.42)	1.96 (4.53)

Population analysed: The result is reported in a "per sequence" format with the different time points at which the interventions were switched. Total of 60 Participants: 32 participants in Group A and 28 participants in Group B.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Day 1 - Day 360 or Early Termination. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Afamelanotide	3 of 100 (3%)	94 of 100 (94%)	Not reported
Placebo	3 of 100 (3%)	88 of 100 (88%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 9521433Dwyer 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.

Related trials for Erythropoietic Protoporphyria

Enrolling by invitationPhase 2/3
HELIOS: Open-Label, Long-Term Extension Study to Investigate the Safety, Tolerability, and Efficacy of DISC-1459 (Bitopertin) in Participants With EPP or XLP
Erythropoietic Protoporphyria
RecruitingPhase 2/3
A Study to Investigate PORT-77 Oral Dosing Compared With Placebo in Participants With Erythropoietic Protoporphyria (EPP) or X-linked Protoporphyria (XLP)
Erythropoietic Protoporphyria (EPP), X-Linked Protoporphyria (XLP)
Active, not recruitingPhase 3
Extension Study to Evaluate Safety and Tolerability of Oral Dersimelagon (MT-7117) in Subjects With Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)
EPP, XLP
RecruitingObservational study
Longitudinal Study of the Porphyrias
Acute Porphyrias, Cutaneous Porphyrias
RecruitingObservational study
Observational Study of Adults and Adolescents With Erythropoietic Protoporphyria (EPP) and X-linked Porphyria (XLP)
Erythropoietic Protoporphyria (EPP), X-Linked Porphyria (XLP)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Head of Clinical Development study director

CLINUVEL PHARMACEUTICALS LTD

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Afamelanotide in people with Erythropoietic Protoporphyria, run by Clinuvel Pharmaceuticals Limited.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cumulative Number of Days of Phototoxic Reactions (Study Efficacy Population) (time frame: 0-360 days or Early Termination). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04053270, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2019.