ThromboGenics Enrolls First Patient in Phase II CIRCLE Trial

13 Jan 2016

ThromboGenics Enrolls First Patient in Phase II CIRCLE Trial Evaluating
Multiple Doses of Ocriplasmin to induce a Total Posterior Vitreous Detachment in Patients with Non-Proliferative Diabetic Retinopathy (NPDR)

Assessing the potential of ocriplasmin to reduce risk of disease progression from NPDR to sight-threatening Proliferative Diabetic Retinopathy (PDR)

Leuven, January 13, 2016 – ThromboGenics NV (Euronext Brussels: THR), an integrated biopharmaceutical company focused on developing and commercializing innovative treatments for diabetic eye disease, today announces that the first patient has been enrolled in its Phase II CIRCLE study evaluating the efficacy and safety of multiple doses of ocriplasmin in inducing total posterior vitreous detachment (PVD) in patients with non-proliferative diabetic retinopathy (NPDR). ThromboGenics hopes to be able to reduce the risk of disease progression to proliferative diabetic retinopathy (PDR) by inducing a total PVD using ocriplasmin. PDR is the major cause of blindness in patients with diabetes. Patients who progress to PDR are at high risk of experiencing severe vision loss or complete blindness.

The CIRCLE study is a Phase II, randomized, double-masked, sham-controlled, multi-center study that will evaluate the efficacy and safety of up to 3 intravitreal injections of either 0.125mg or 0.0625mg of ocriplasmin in subjects with moderately severe to very severe NPDR, to induce total PVD in order to reduce the risk of the patient developing sight-threatening PDR.

A total of 230 subjects will be recruited into the CIRCLE trial, approximately 92 in each ocriplasmin arm (0.125mg or 0.0625mg) and 46 in the sham arm, over the next 12 months. Patients will be accrued from sites across the US, Canada and EMEA.

The primary endpoint of the CIRCLE study is the percentage of patients with total PVD by the month 3 visit, confirmed by both B-scan ultrasound and SD-OCT.

The study has a number of exploratory secondary endpoints that are designed to provide further insight into ocriplasmin’s potential in reducing the risk of progression of NPDR to PDR.

For each patient recruited, the CIRCLE study duration will be approximately 24 months from the first injection. The first results are anticipated to be available in the second half of 2017.

Research has suggested that total PVD, a complete separation of vitreous and retina, could prevent the progression of NPDR to PDR. This could be explained by total PVD leading to elimination of the scaffold needed for the development of new blood vessels and/or the improvement of oxygen supply to the retina, thereby reducing retinal ischemia, production of VEGF, vascular outgrowth and neovascularization.

Diabetic retinopathy (DR) is the leading cause of visual disability and blindness among professionally active adults1 . Worldwide, the prevalence rate of vision-threatening PDR or diabetic macular edema (DME) was estimated to be 11.72% of the diabetic population in 20102 .

A recent report from the American Academy of Ophthalmology has projected that the prevalence of individuals with any form of diabetic retinopathy in the United States in the year 2020 will be 6 million people, of whom 1.34 million persons will have vision-threatening DR3 (PDR or diabetic macular edema (DME)).

David Scales, MD - Principal Investigator at Foreseight Studies, LLC in San Antonio, Texas, USA for the Circle Study said, “I am delighted that we have recruited the first patient in this important study. There is a clear medical need for a treatment option that is able to prevent patients with NPDR progressing to PDR, a disease state that could result in them losing their sight. Achieving this, by using up to 3 doses of ocriplasmin to generate a total PVD pharmacologically, would be a major advance in the overall treatment of diabetic retinopathy.”

Dr Patrik De Haes, CEO of ThromboGenics, commenting on today’s announcement, “The start of the CIRCLE study is a major milestone for ThromboGenics as we focus our research efforts on delivering important advances in the treatment of diabetic eye disease. The CIRCLE trial is designed to show that multiple doses of either 0.125mg or 0.0625mg of ocriplasmin can generate total PVD in patients with NPDR. We hope that by using ocriplasmin to generate PVD, we can prevent a significant number of patients with NPDR experiencing their disease progressing to PDR, which could potentially lead to them losing their sight.”

 

1  Cunha-Vaz J (1998). Lowering the risk of visual impairment and blindness. Diabet Med. 15 (Suppl 4): S47-50.
2  Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, Chen SJ, Dekker JM, Fletcher A, Grauslund J, Haffner S, Hamman RF, Ikram MK, Kayama T, Klein BE, Klein R, Krishnaiah S, Mayurasakorn K, O'Hare JP, Orchard TJ, Porta M, Rema M, Roy MS, Sharma T, Shaw J, Taylor H, Tielsch JM, Varma R, Wang JJ, Wang N, West S, Xu L, Yasuda M, Zhang X, Mitchell P, Wong TY; Meta-Analysis for Eye Disease (META-EYE) Study Group (2012). Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 35 (3): 556-564.

3 http://www.aao.org/preferred-practice-pattern/diabetic-retinopathy-ppp--2014