1 / 22

The BLAST Trial B iorest L iposomal A lendronate with S tenting s T udy

The BLAST Trial B iorest L iposomal A lendronate with S tenting s T udy. Targeted Anti-Inflammatory Systemic Therapy for Restenosis. Shmuel Banai, MD Tel Aviv medical Center Tel Aviv, ISRAEL. Disclosure Statement of Financial Interest.

Rita
Download Presentation

The BLAST Trial B iorest L iposomal A lendronate with S tenting s T udy

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. The BLAST TrialBiorestLiposomal Alendronate with StentingsTudy Targeted Anti-Inflammatory Systemic Therapy for Restenosis Shmuel Banai, MD Tel Aviv medical Center Tel Aviv, ISRAEL

  2. Disclosure Statement of Financial Interest I, Shmuel Banai, DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

  3. Background Inflammation is the hallmark of Atherosclerosis and Restenosis Monocytes/macrophages are the key mediators of inflammation systemically and locally within the vessel wall Patients in a pro-inflammatory state are at higher risk for Restenosis

  4. (1) Free Bisphosphonates (BPs) can not cross cell membranes (2) Unique Liposomes as Trojan horses; Encapsulated BP are phagocytosed exclusively by monocytes Targeting Monocytes (3) Liposome degradation in lysosome releases BP (4) Intracellular BPs inhibit the cell

  5. BIOrest LABR-312 Cell # [% of baseline] Monocyte Modulation 0 1 5 10 50 100 Concentration [uM] Days after Infusion • A highly selective systemic monocyte inhibitor • Produces a transient effect lasting several days EC Macrophages 0 2 4 6 Danenberg et al, Circulation 2002 Danenberg et al, Circulation 2003 Danenberg et al, JCP 2003

  6. BLAST – BIOrestLiposomal Alendronate with StentingsTudy BIOrest LABR-312 is a unique, specific and transient means of modulating monocytes HYPOTHESIS: Modulation of systemic and local inflammation will attenuate intimal hyperplasia after BMS implantation OBJECTIVE: To assess the safety and efficacy of a single IV bolus of LABR-312 in the treatment of de novostenotic lesions in native coronary arteries in a population undergoing PCI with implantation of a BMS

  7. BLAST Trial Phase II dose-finding, randomized, multi-center, prospective, double blind. N=225 Patients Study PI: Prof. Shmuel Banai – Tel Aviv Medical Center Participating Medical Centers and PI’s: • Tel Aviv Sourasky – S. Banai • ShaareZedek – Y. Almagor • Baruch Padeh – Y. Hasin • Bnei Zion – U. Rosenschein • Rabin – R. Kornowski • Sheba – V. Guetta • Lady Davis – B. Lewis • Meir – M. Mosseri • Kaplan – O. Ayzenberg • Hillel Yaffe – A. Frimerman • Western Galilee – S. Atar

  8. BLAST Trial – Parties Involved

  9. BLAST Trial - Study Endpoints Primary Endpoint: In-Stent angiographic Late Loss @ 6m (High / Low Dose vs. Placebo) Secondary endpoints: IVUS measurements, clinical outcomes, monocytecount and function by FACS (Fluorescence Activated Cell Sorter) Pre-Specified subgroup analyses including: Diabetes Baseline monocyte count Unstable Angina

  10. Total Patients Recruited N=225 Randomization 1:1:1 Placebo (saline) N=74 High Dose (10µg LABR-312) N=74 Low Dose (1µg LABR-312) N=77 BMS Stenting (Pressilion)+Drug Administration QCA, IVUS, Blood sampling for monocytes @ Screening, 0, 8, 16, 24 h 30d Clinical f/u 1º Endpt 6m Clinical+Angiographic f/u Per-Protocol Analysis on a per-patient basis Placebo N=57 (77% f/u) High Dose N=59 (80% f/u) Low Dose N=56 (73% f/u) 6m IVUS f/u subset Placebo N=26 High Dose N=26 Low Dose N=31

  11. Main Inclusion/Exclusion Criteria De-novo lesions in native coronary arteries LL<30mm, 2.5mm<RVD<3.5mm, 1 or 2 VD No bifurcations, LM, Ostial Up to 3XULN cTn  DM  NSTEMI  Unstable Angina Pro-Inflammatory Patients

  12. Baseline Patient Characteristics

  13. Baseline Lesion Characteristics

  14. BLAST Trial Main Safety Results CEC Adjudicated @ 180d * MI excluding peri-procedural = 1.8%, 1.8%, 1.7% Placebo, Low Dose, High Dose respectively

  15. BLAST Trial Main Efficacy Results

  16. But are they truly the same? Non-Gaussian p<0.005 Gaussian p>0.25

  17. Cumulative Distributions At 6 month follow up

  18. Hypothesized Differential Response : Gaussian Single peak : Non-Gaussian Left-skewed/double peak

  19. Protocol mandated sub-group analysis Pre-hoc analysis based on inflammatory state • Diabetes • Baseline monocyte count

  20. Diabetic Subgroup

  21. Pre-Specified Inflammatory Subgroup 50-50 Split based on baseline monocyte count * Low Monocytes = Less than median value pre-injection ** High Monocytes = More than median value pre-injection

  22. Conclusions There were no safety concerns associated with BIOrest LABR-312 In the total study cohort, LABR-312 had no overall effect on in-stent Late Loss, the primary endpoint In the pro-inflammatory patients (mandated subgroup analysis including >50% of the cohort), there was a statistically significant and clinically meaningful reduction in Late Loss with LABR-312 This differential response could be identified and predicted a-priori, providing the potential for personalized medicine Future clinical trials will focus on the documented clinical effect in pro-inflammatory patients

More Related