Clinical trial NCT01086761: Study of MP0112 Intravitreal Injection in Patients With Wet Age Related Macular Degeneration
Official title: A Phase I/II, Open-label, Non-controlled, Escalating Dose, Multicentre Clinical Trial Evaluating the Safety, Preliminary Efficacy, and Pharmacokinetics of MP0112 Injected Intravitreally in Patients With Wet Age Related Macular Degeneration (AMD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Wet Age-Related Macular Degeneration
Lead sponsor: Allergan
Sponsor class: INDUSTRY
Collaborators: name: Molecular Partners AG
First posted: 2010-03-15
Enrollment: 32
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and tolerability of MP0112 (a novel, potentially long acting VEGF inhibitor) in patients with wet Age Related Macular Degeneration.


Eligibility criteria: Inclusion Criteria:

* Clinical signs and angiographic evidence of active primary progressive subfoveal choroidal neovascularisation (CNV), including juxtafoveal lesions that affect the fovea on FA in the study eye that is at least 50% of the total lesion area
* ETDRS best-corrected visual acuity of: 20/40 to 20/320 in the study eye at 4 meters
* Male or female age \> 50 years
* Written informed consent prior to any study procedures
* Willing, committed, and able to return for ALL clinic visits and complete all study-related procedures.

Exclusion Criteria:

* Prior treatment with anti-VEGF therapy in the study eye, including bevacizumab, ranibizumab, or pegaptanib, as well as photodynamic therapy with verteporfin
* Any prior or concomitant therapy with another investigational agent to treat neovascular AMD in the study eye, except dietary supplements or vitamins
* Subfoveal thermal laser therapy, external-beam radiation therapy, or transpupillary thermotherapy in the study eye
* Extrafoveal laser coagulation treatment within 12 weeks prior to Baseline in the study eye
* Total lesion size \> 20mm2 (including blood, scars and neovascularization) as assessed by FA in the study eye
* Subretinal hemorrhage that is either 50% or more of the total lesion area, or if the blood is under the fovea and is 2.54mm2 or more in size in the study eye
* Scar or fibrosis, making up \> 50% of total lesion in the study eye
* Scar, fibrosis, or atrophy involving the center of the fovea
* Presence of retinal pigment epithelial tears or rips
* History of any vitreous hemorrhage within 4 weeks prior to Visit 1 or current hemorrhage in the study eye
* Presence of other causes of CNV, including pathologic myopia (spherical equivalent of -8 diopters or more negative, or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye
* History or clinical evidence of diabetic retinopathy, diabetic macular oedema or any other vascular disease affecting the retina, other than AMD, in either eye
* Prior vitrectomy in the study eye
* History of retinal detachment or treatment or surgery for retinal detachment in the study eye
* Ocular surgery (including cataract removal) in the study eye within 3 months of enrolment
* Active intraocular inflammation (grade trace or above) in the study eye
* History of allergy to any components of the study drug or diagnostic devices, such as fluorescein
* Advanced glaucoma or intraocular pressure above 22 mmHg in the study eye despite treatment
* Inability to obtain fundus photographs or fluorescein angiogram of sufficient quality to be analyzed and graded by the central reading center
* History of idiopathic or autoimmune-associated uveitis in either eye
* Infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye
* Aphakia or absence of the posterior capsule in the study eye
* Presence of a non-healing wound, ulcer, fracture or any other medical condition associated with bleeding
* Use of antimitotic or antimetabolite therapy within 30 days or 5 elimination half-lives of enrolment
* Premenopausal women
* Any disorder or condition that contraindicates the use of an investigational drug
* Participation in another investigational drug study within 3 months of enrolment
* Uncontrolled hypertension
* Previous stroke within 12 months of study entry
* Systemic treatment with any anti-VEGF drug
* Current treatment for active systemic infection

Primary outcomes:
measure: Maximal Tolerated Dose (MTD) Following a Single Injection
timeFrame: 16 weeks
Secondary outcomes:
measure: Percentage of Participants With Stable or Improved Best Corrected Visual Acuity (BCVA)
timeFrame: Baseline, Week 4
measure: Change From Baseline in Central Area Retinal Thickness
timeFrame: Baseline, Week 4
measure: Area of Leakage as Measured by Fluorescein Angiography
timeFrame: Baseline, Week 4
measure: Area of Lesion as Measured by Fluorescein Angiography
timeFrame: Baseline, Week 4
measure: Maximum Serum Concentration (Cmax) of MP0112 at Day 3
timeFrame: Day 3
measure: Number of Participants With Positive Binding Anti-MP0112 Antibodies
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Brno
country: Czech Republic
facility: Fakultni Nemocnice Brno
state: Czech
city: Olomouc
country: Czech Republic
facility: Fakultni Nemocnice Olomouc
state: Czech
city: Praha
country: Czech Republic
facility: Ustrendi Vojenska Nemocnice
state: Czech
city: Creteil
country: France
facility: Hopital Intercommunual de Creteil
city: Lyon
country: France
facility: Centre Rabelais
city: Marseille
country: France
facility: Centre Paradis-Monticelli
city: Strasbourg
country: France
facility: Hopitaux Universitaires
city: Bern
country: Switzerland
facility: Inselspital
Study officials:
References:
citation: Souied EH, Devin F, Mauget-Faysse M, Kolar P, Wolf-Schnurrbusch U, Framme C, Gaucher D, Querques G, Stumpp MT, Wolf S; MP0112 Study Group. Treatment of exudative age-related macular degeneration with a designed ankyrin repeat protein that binds vascular endothelial growth factor: a phase I/II study. Am J Ophthalmol. 2014 Oct;158(4):724-732.e2. doi: 10.1016/j.ajo.2014.05.037. Epub 2014 Jun 5.