A Clinical Trial to Assess the Safety and Efficacy of Intravitreous Administration of Zimura in Subjects with Autosomal Recessive Stargardt Disease

• Register: EUCTR
• Last refreshed on: 11 June 2018
• Main ID: EUCTR2017-004783-35-ES
• Date of registration: 02/02/2018
• Prospective Registration: Yes
• Primary sponsor: OPHTHOTECH CORPORATION
• Public title: A Clinical Trial to Assess the Safety and Efficacy of Intravitreous Administration of Zimura in Subjects with Autosomal Recessive Stargardt Disease
• Scientific title: A Phase 2b Randomized, Double-masked, Controlled Trial to Establish the Safety and Efficacy of Zimura™ (Complement C5 Inhibitor) Compared to Sham in Subjects with Autosomal Recessive Stargardt Disease
• Date of first enrolment: 09/04/2018
• Target sample size: 120
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004783-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: Zimura and sham administered by an unmasked investigator; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, France, Germany, Hungary, Israel, Italy, Spain, United Kingdom, United States

Contacts

• Name: Patricia Johnson
• Affiliation: OPHTHOTECH CORPORATION

• Name: Patricia Johnson
• Affiliation: OPHTHOTECH CORPORATION

Key inclusion & exclusion criteria

Inclusion criteria:
Ophthalmic Inclusion Criteria
The following inclusion criteria apply to the study eye:
- At least two pathogenic mutations of ABCA4 gene confirmed by a CLIA-certified laboratory.
- Best corrected visual acuity in the study eye between 20/20 - 20/200 Snellen equivalent, inclusive.
- Presence of at least one identifiable location of at least 250 micrometers contiguous width of ellipsoid zone loss on SD-OCT within the total 9 ETDRS subfields.
- The total area of thinned layer(s) on OCT not extending beyond the outer ring of the total 9 ETDRS subfields (e.g. not extending beyond fields 5-9).
- Fundus autofluorescence may show heterogeneous signals (areas of increased and/or decreased autofluorescence) but no area of subfoveal definitely decreased autofluorescence (DDAF).
- Clear ocular media and adequate pupillary dilatation in both eyes (OU) to allow for all imaging procedures, including good quality stereoscopic fundus photography, fundus autofluorescence, and spectral domain ocular coherence tomography.
- Intraocular pressure of 21 mmHg or less in the study eye.
General Inclusion Criteria
- Subjects of either gender aged between 18 and 50 years, inclusive.
- Women must be using two forms of effective contraception, be post-menopausal for at least 12 months prior to trial entry, or surgically sterile; if of child-bearing potential, a serum pregnancy test must be performed within 14 days prior to the first injection with a negative result. The two forms of effective contraception must be implemented during the trial and for at least 90 days following the last dose of test medication. Male subjects should use a condom during the time of study drug exposure and for 90 days following last exposure of study drug.
- Provide written informed consent.
- Ability to return for all trial visits.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects will not be eligible for the trial if subjects cannot attend all of the trial required visits, or if any of the following criteria are present in the study eye or systematically:

Ophthalmic Exclusion Criteria
- Macular atrophy secondary to any condition other than STGD1 in either eye (e.g., drug-induced).
- Any prior treatment for STGD1 including gene therapy, stem cell therapy or any prior intravitreal treatment for any indication in either eye.
- Participation in an interventional study of a vitamin A derivative = 3 months prior to screening.
- Any ocular condition in the study eye that would progress during the course of the study that could affect central vision, microperimetry testing or otherwise be a confounding factor.
- Concomitant treatment with any ocular or systemic medication that is known to be toxic to the lens, retina or optic nerve.
- Presence of intraocular inflammation (= trace cell or flare), macular hole, pathologic myopia (spherical equivalent of -8 diopters or more negative, or axial length of 25mm or more), epiretinal membrane, evidence of significant vitreo-macular traction, vitreous hemorrhage or aphakia (pseudophakia with or without an intact capsule is not an exclusion criteria).
- Presence or history of idiopathic or autoimmune-associated uveitis in either eye.
- Significant media opacities, including cataract, which might interfere with visual acuity, assessment of toxicity, fundus photography or fundus autofluorescence. Subjects should not be entered if there is likelihood that they will require cataract surgery in the study eye during the study.
- Any intraocular surgery or thermal laser within 3 months of trial entry. Any prior thermal laser in the macular region, regardless of indication.
- Any ocular or periocular infection or ocular surface inflammation in the past 12 weeks.
- History of any of the following procedures: Posterior vitrectomy, filtering surgery (e.g. trabeculectomy), glaucoma drainage device, corneal transplant or retinal detachment.

General Exclusion Criteria
- Any of the following underlying diseases including:
• Diabetes mellitus (regardless of HbA1c level)
• HbA1c value of =6.5%*:
• If the HbA1c value is = 6.5% and = 6.9%, and the patient has no signs or symptoms of diabetes mellitus, has a normal creatinine, has no diabetic retinopathy and no glycosuria, then the patient may have an oral glucose tolerance test (OGTT) at the discretion of the investigator. If the 2-hour glucose value on OGTT is <200 mg/dL (<11.1mmol/L), then the patient may be enrolled.
• History of other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk for treatment complications.
• History or evidence of severe cardiac disease (eg, New York Heart Association (NYHA) Functional Class III or IV - see Appendix 17.5), history or clinical evidence of unstable angina, acute coronary syndrome, myocardial infarction or revascularization within last 6 months, ventricular tachyarrhythmia requiring ongoing treatment.
• Subjects with a clinically significant laboratory value. Laboratory tests may be repeated once before randomization.
• Stroke within 12 months of trial entry.
• Any major surgical procedure within one month of tri

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Eye Diseases [C11]

Autosomal Recessive Stargardt Disease
MedDRA version: 20.1 Level: PT Classification code 10062766 Term: Stargardt's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: Zimura
Product Code: ARC1905
Pharmaceutical Form: Solution for injection
INN or Proposed INN: avacincaptad pegol
Current Sponsor code: ARC1905
Other descriptive name: ARC1905 20 MG/ML
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Primary end point(s): Primary Efficacy Endpoint
• Mean rate of change in the area of ellipsoid zone defect measured by en face SD-OCT over 18 months.

Safety Endpoints:
• Adverse events, vital signs, ophthalmic variables [ophthalmic examination, intraocular pressure (IOP), fluorescein angiogram (FA), fundus autofluorescence (FAF), spectral domain-optical coherence tomography (SD-OCT), microperimetry], electrocardiogram (ECG), and laboratory variables.

Main Objective: The objectives of this study are to evaluate the safety and efficacy of Zimura™ intravitreal injection compared to Sham in subjects with autosomal recessive Stargardt disease 1 (STGD1).

Secondary Objective: Not applicable

Timepoint(s) of evaluation of this end point: Baseline to Month 18

Secondary Outcome(s)

Secondary end point(s): Secondary and Supportive Endpoints
• Mean rate of change in the horizontal width of undetectable ellipsoid zone measured by a horizontal scan through the foveal center with SD-OCT over 18 months.
• Mean rate of change in the area of atrophic lesion (definite decrease in autofluorescence, DDAF) over 18 months measured by fundus autofluorescence (FAF).
• Mean change in photopic and/or mesopic macular sensitivity measured by microperimetry from Baseline to Month 18.
• Mean rate of change in the thickness of the outer nuclear layer measured by a horizontal scan through the foveal center at the position of maximum width of ellipsoid zone loss at Baseline over 18 months measured by SD-OCT.
• Mean change in best corrected visual acuity (Early Treatment Diabetic Retinopathy Study [ETDRS] letters) from Baseline to Month 18.
• Emergence of at least one new atrophic lesion (DDAF) over 18 months measured by FAF at Month 18.

Timepoint(s) of evaluation of this end point: Baseline to Month 18

Secondary ID(s)

OPH2005

2017-004783-35-HU

Source(s) of Monetary Support

OPHTHOTECH CORPORATION