Clinical Trials

Date: 2013-02-04

Type of information:

phase: 2


Company: Medigene (Germany)

Product: RhuDex®

Action mechanism: RhuDex® is a CD80 antagonist that blocks undesired T-cell activation and thus has an immunomodulating and anti-inflammatory effect. Therefore, this drug candidate can be classified with the group of “Disease-Modifying Antirheumatic Drugs” (DMARDs). In a phase IIa trial in 29 patients in the indication rheumatoid arthritis, RhuDex® showed initial signs of biological activity.

Disease: primary biliary cirrhosis
rheumatoid arthritis

Therapeutic area: Autoimmune diseases - Inflammatory diseases - Liver diseases - Rheumatic diseases


Trial details: RhuDex® RapidFACT™ formulation study: During the recently completed clinical formulation study, variations of a RhuDex® formulation were given subsequently in single dose applications to ten healthy volunteers. Due to the innovative RapidFACT™ (Rapid Formulation Development and Clinical Testing) study design, variants of formulations could be tested and evaluated for their tolerability and pharmacokinetic profile over a short period of time, since the respective formulation variant was produced immediately prior to dosing.  All formulations investigated showed an excellent tolerability profile. The final formulation demonstrates the most advantageous prolongation of plasma absorption and elimination phases to achieve steady compound plasma levels with repeat daily dosing. Due to the highly flexible study design, additional preliminary data on the effect of concomitant food intake (\"food effect\") and on dose proportionality have also been obtained.

Latest news:

* On February 4, 2013, Medigene has announced that it has decided to expand the clinical development plan for RhuDex® in the treatment of autoimmune diseases. Following recommendations of the regulatory authorities and the Steering Committee, the planned phase IIa trial in the indication of primary biliary cirrhosis (PBC) is to be expanded from a three-arm to a four arm, controlled study and the planned treatment period for patients will be extended from three to six months. The aim is to increase the information value of the trial data collected in order to confirm the mode of action of RhuDex® in autoimmune diseases and facilitate the future approval of RhuDex® for PBC. This is expected to further increase the value of the drug candidate in both scientific and commercial terms.
Medigene will now develop the modified trial design. Subject to the successful completion of the necessary preparatory work and the approval of the study by the regulatory authorities, the start of this expanded phase II trial is scheduled for the first half of 2014 at the latest. It will replace the phase IIa trial with RhuDex® originally planned for 2013. As a result, the major financial expenses relating to a phase II trial will be deferred to 2014 and thereafter. On the occasion of the publication of the Company's annual report on March 22, 2013, Medigene will provide further details of the development strategy for RhuDex® and the Company' s financial outlook.
* On June 21, 2012, Medigene has announced that the clinical formulation trial with RhuDex® achieved positive results and that the further clinical development of RhuDex® for the treatment of autoimmune diseases will continue with an optimized oral formulation. As the next development step, Medigene plans to initiate a phase II proof-of-concept study in primary biliary cirrhosis (PBC) before the end of 2012 to verify both the mechanism of action and the overall clinical profile of RhuDex® for the treatment of autoimmune diseases. The study results are expected to build a basis for the further development in rheumatoid arthritis.
Dr. Frank Mathias, CEO of Medigene AG, comments: „Medigene has developed a logical and integrated non-clinical and clinical program for RhuDex®. We have a new, optimized formulation for this candidate and now want to prove the clinical relevance of RhuDex®’s mode of action as quickly as possible. The PBC indication offers an extremely useful and rapid way to achieve this goal. The results will be highly valuable for the further development of RhuDex® in the treatment of rheumatoid arthritis.\"
The objective of the clinical formulation trial was to develop an optimized oral formulation of the active substance suitable for the treatment of chronic diseases. All endpoints of the study were met. The new formulation is characterized by an optimized pharmacokinetic profile, excellent tolerability and a reduction of dose units. Based on the results of this study, RhuDex® will now be administered in a formulation based on Gelucire. This excipient is a known lipid-based compound belonging to the group of excipients \"generally regarded as safe\" (GRAS), and is used in marketed drug formulations.
With the new formulation, Medigene plans to initiate a phase II clinical proof-of-concept study with RhuDex® for the treatment of autoimmune diseases. Medigene will conduct this study in the indication of primary biliary cirrhosis (PBC), allowing the company to generate widely accepted clinical data on relevant disease parameter modification after only three months of treatment. In addition, patients with PBC do not receive explicit immunomodulating baseline therapy, as is the case, for example, in the treatment of rheumatoid arthritis. Thus, this patient group is suitable to preliminarily confirm that RhuDex®, due to its specific mode of action, does not adversely affect the ability to mount a spontaneous inflammatory reaction. Therefore, this clinical study is an important step for the further development of RhuDex® in the treatment of rheumatoid arthritis.
In parallel to the planned initiation of this proof-of-concept study, Medigene has initiated additional regulatory non-clinical studies to enable the necessary chronic treatment of patients with autoimmune diseases. Also, non-clinical studies are being conducted to integrate additional translational aspects into clinical development.

Is general: Yes