The objectives of the study are to evaluate the following in patients with a documented history of EPP:•determine whether CUV1647 can reduce the number of phototoxic reactions in patients with EPP•determine whether CUV1647 can reduce the severity of…
ID
Source
Brief title
Condition
- Metabolic and nutritional disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
•Number and severity of phototoxic reactions
Secondary outcome
•Melanin density (measured by spectrophotometry)
•Duration of sunlight exposure, as recorded in patient diary
•Quality of life measured with SF36 questionnaire
•*Time taken to develop provoked symptoms* following phototesting (in a subset
of patients only)
•Treatment-emergent adverse events (coded as MedDRA Preferred Terms)
•Changes in hematology, serum chemistry and urinalysis measurements from
Screening to Study Days 1, 61, 121, 181, 241 and 301.
Background summary
The investigational product is a small solid implant containing a mixture of
the active ingredient, CUV1647 [(Nle4, D-Phe7)-α-MSH] and polylactic acid.
CUV1647 is a synthetic analogue of the naturally occurring melanotropin, α-MSH,
an agonist for melanogenesis. The CUV1647 16 mg sustained release implant is
administered into the suprailiac crest.
Study objective
The objectives of the study are to evaluate the following in patients with a
documented history of EPP:
•determine whether CUV1647 can reduce the number of phototoxic reactions in
patients with EPP
•determine whether CUV1647 can reduce the severity of phototoxic reactions in
patients with EPP
•determine whether CUV1647 can increase the duration of sunlight tolerated by
EPP patients
•determine whether CUV1647 increases melanin density in the skin at several
specified body sites
•evaluate the safety and tolerability of CUV1647 by measuring
treatment-emergent adverse events (AEs)
•determine whether CUV1647 can improve the quality of life of EPP patients
•in a subset of patients, determine whether CUV1647 implants can reduce the
susceptibility to provocation with a standardized light source (time to
appearance of provoked symptoms) - this part of the study will not be performed
in the Netherlands
Study design
This is a randomized placebo-controlled study to be conducted in two parallel
study arms with crossover between treatments every 60 days. Approximately 10
eligible patients per centre will be enrolled and will receive CUV1647 (16 mg
implants) or placebo according to the following dosing regime:
- Group A will be administered active implants on Days 0, 120, 240 and placebo
implants on Days 60, 180, 300
- Group B will be administered placebo implants on Days 0, 120, 240 and active
implants on Days 60, 180, 300
To determine eligibility for study inclusion, patients will undergo a screening
evaluation 7 days prior to the administration of the first dose. The number
and severity of phototoxic reactions, skin melanin density (measured by
spectrophotometry) will be determined at all clinic visits while the duration
of sun exposure, treatment-emergent adverse events and the use of rescue
medication will be recorded in patient diaries. Quality of life will be
measured on Day 0 and again at the end of each treatment period. Participants
will visit the clinic on Days 0, 14, 30, 60, 74, 90, 120, 150, 180, 210, 240,
270, 300, 330 and 360 for assessments of adverse events. In addition, follow
up home/clinic visits will be scheduled for 24 hours after administration of
each implant to collect blood samples for safety and to obtain specimens for
urinalysis.
In two of the centers abroad, a subset of the included patients will be
phototested, and a *time taken to develop provoked symptoms* determined on the
dorsal surface of one hand. Patients, which will be treated in the Netherlands,
will not participate in this additional part of the study.
An Interim Efficacy Analysis will be undertaken after all participants have
completed all Day 120 (Part I) requirements and the results of this analysis
reviewed by a Data and Safety Monitoring Board or Independent Data Review
Committee.
Intervention
Patients will receive CUV1647 (16 mg implants) or placebo according to the
following dosing regime:
- Group A will be administered active implants on Days 0, 120, 240 and placebo
implants on Days 60, 180, 300
- Group B will be administered placebo implants on Days 0, 120, 240 and active
implants on Days 60, 180, 300
To determine eligibility for study inclusion, patients will undergo a screening
evaluation 7 days prior to the administration of the first dose. The number
and severity of phototoxic reactions, skin melanin density (measured by
spectrophotometry) will be determined at all clinic visits while the duration
of sun exposure, treatment-emergent adverse events and the use of rescue
medication will be recorded in patient diaries. Quality of life will be
measured on Day 0 and again at the end of each treatment period. Participants
will visit the clinic on Days 0, 14, 30, 60, 74, 90, 120, 150, 180, 210, 240,
270, 300, 330 and 360 for assessments of adverse events. In addition, follow
up home/clinic visits will be scheduled for 24 hours after administration of
each implant to collect blood samples for safety and to obtain specimens for
urinalysis.
In two of the centers abroad, a subset of the included patients will be
phototested, and a *time taken to develop provoked symptoms* determined on the
dorsal surface of one hand. Patients, which will be treated in the Netherlands,
will not participate in this additional part of the study.
An Interim Efficacy Analysis will be undertaken after all participants have
completed all Day 120 (Part I) requirements and the results of this analysis
reviewed by a Data and Safety Monitoring Board or Independent Data Review
Committee.
Study burden and risks
Not Applicable
level 11, 330 Collins Street, Melbourne, VIC
3000
AU
level 11, 330 Collins Street, Melbourne, VIC
3000
AU
Listed location countries
Age
Inclusion criteria
-Male or female subjects with a diagnosis of EPP (confirmed by elevated free protoporphyrin in peripheral erythrocytes)
Exclusion criteria
-Allergy to CUV1647 or the polymer contained in the implant or to lignocaine or other local anaesthetic 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.
-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-Jaegher 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 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).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | ACTRN012607000261415 |
| EudraCT | EUCTR2007-000636-13-NL |
| CCMO | NL18784.078.08 |