Clinical Trials

Date: 2018-04-27

Type of information: Recruitment of the first patient

phase: 2

Announcement: recruitment of the first patient

Company: Thrombogenics (Belgium)

Product: THR-317 and ranibizumab

Action mechanism:

monoclonal antibody.
THR-317 (anti-PIGF) is a recombinant human monoclonal antibody directed against the receptor-binding site of human placental growth factor (PlGF).
In pre-clinical models, anti-PlGF has been shown, in addition to anti-angiogenic and anti-edema properties, to also be anti-inflammatory.
The product is an ophthalmologic formulation of TB-403, that has been developed by the Swedish biotech Bioinvent. ThromboGenics carries all costs for the development of THR-317 and BioInvent is entitled to five percent of the project's economic value.
Ranibizumab is a recombinant humanized monoclonal antibody fragment (lacking a Fc region). This is the first VEGF inhibitor specifically designed for use in the eye to bind to and inhibit VEGF-A, a protein that is believed to play a critical role in the formation of new blood vessels (angiogenesis) and the hyperpermeability (leakiness) of the vessels.
Simultaneous inhibition of VEGF (ranibizumab) and PlGF (THR-317) may have a better efficacy than either treatment alone. Non-clinical experiments indicate that anti-PlGF in the presence of an anti-VEGF antibody has an additive effect inhibiting the growth of new blood vessels (Van de Veire et al., 2010), a disease hallmark of DME. This may mean that a combination approach could result in a better treatment response. The anti-PlGF component could bring the advantage of reduced inflammation associated with a reduced level of PIGF (van Bergen et al., 2017).

Disease: diabetic macular edema

Therapeutic area: Ophtalmological diseases

Country: Belgium, France, Germany, Slovakia, Spain, UK

Trial details:

This study is conducted to evaluate the safety of intravitreal THR-317 administered in combination with ranibizumab, and to assess the efficacy of the combination treatment in improving best-corrected visual acuity (BCVA) and reducing central subfield thickness (CST), in subjects with central-involved diabetic macular oedema (CI-DME). (NCT03499223)

Latest news:

• On April 27 2018, ThromboGenics announced that it has successfully enrolled the first patient in a Phase 2 active-controlled, masked, multicenter study to evaluate the efficacy and safety of THR-317 administered in combination with ranibizumab (Lucentis®, Novartis), for the treatment of diabetic macular edema (DME).
This Phase 2 clinical study (THR-317-002) is designed to evaluate the safety and efficacy of IVT THR-317 along with ranibizumab, compared with ranibizumab monotherapy in patients with DME.
Patients will be randomized into either a combination arm of THR-317 (8mg) + ranibizumab, or ranibizumab plus a sham administration. The primary outcome measure is change from baseline in Best Corrected Visual Acuity (BCVA) at Month 3. Approximately 70 patients will be enrolled, of which about half will be anti-VEGF treatment naïve and the other half will have had a sub-optimal response to prior treatment with ranibizumab.
Initial results from the THR-317-002 study are anticipated in Q3 2019.