Safety evalution of cardiovascular data from a first in man bayesian approach clinical trial (proof of concept trial) of EP 1645 - an Anti-CD4MAB-Fragment - for imaging chronic inflammation in patients with active rheumatoid arthritis

Dr. Siegert, Joachim1, Dr. Hesse, Swen2, Dr. Schindler, Christoph1, Brecht, Beate1, Dr. Wirkner, Kerstin3, Dr. Pigla, Ullrich3, Prof. Dr. Sabri, Osama2, Prof. Dr. Kirch, Wilhelm1. 1Institute of Clinical Pharmacology, Medical Faculty, Technical University Dresden, Dresden, Germany, Fiedlerstrasse 27, 01307 Dresden, Germany; 2Klinik und Poliklinik for Nuclear Medicine, University of Leipzig, Leipzig, Germany, Stephanstr. 11, 04103 Leipzig, Germany; 3Biotectid GmbH, Deutscher Platz 5 c, 04103 Leipzig, Germany.

New drugs have to demonstrate aside efficacy their safety. First in man studies include thereby many safety parameters to evaluate physiological function to become acquainted with potential risks for adverse events.

Data from a first in man clinical trial of EP 1645 (a CD4mAb-Fragment to be labeled with 99mTc) to be developed as a diagnostic tool for an effective and reliable diagnostic to identify patients with active rheumatoid arthritis were evaluated concerning cardiovascular effects.

Methods: During open single-dose, adaptive design phase I study performed in otherwise “healthy” volunteers (50-80 years, 5 of potentially 11 volunteers), who suffered from joint disease due to rheumatoid arthritis 2 Patients were dosed with approx. 370 MBq whereas 3 Patients received approx. 640 MBq (due to the addaptive design the goal of the trial was reached at this step). In all these 5 patients prior to and up to 14 d after i.v. administration of EP 1645 physical examination, vital signs, ECG, lab tests, HAMA and AE/SAE reporting were conducted and documented.

Results: The baseline examination revealed hypertension in 2 of 5 patients and atrial fibrillation and flutter in 1 of 5. During the study no SAE and only one AE (slight extrasystolic rhythm at one nocturnal time point, without recurrence at later examinations) were recorded. This AE was regarded as not to be causally related to the study drug. No significant changes in ECG, heart rate, blood pressure, lab values, HAMA titres were observed.

Discussion: KP-EP 1645 was safe and well tolerated. No serious adverse event was observed during the trial. The data were unsuggestive of any cardiovascular risks.