GENEVA, November 17, 2010 /PRNewswire/ -- Merck Serono, a division of Merck KGaA, Darmstadt, Germany, announced today the completion of patient enrollment in the ORACLE MS 1 clinical study. This randomized, double blind, placebo-controlled, international Phase III trial is designed to evaluate the therapeutic effects of Cladribine Tablets on the time to conversion to multiple sclerosis (MS) in people with a first clinical event suggestive of the disease. A total of 617 patients considered at high risk of developing MS due to a recently experienced isolated demyelinating event and having magnetic resonance imaging (MRI) brain scans consistent with early signs of MS were randomized in the study.
"The clinical development program of Cladribine Tablets is designed to characterize the potential therapeutic effects of Cladribine Tablets therapy at the various stages of multiple sclerosis," said Dr. Bruno Musch, Merck Serono's Head of Global Clinical Development Neurodegenerative Diseases. "The completion of patient enrollment in the ORACLE MS study is a significant milestone as this study will provide insight on the impact of Cladribine Tablets therapy on the course of multiple sclerosis when administered early in the disease process."
Besides the ORACLE MS study, the Phase III program of Cladribine Tablets includes the completed CLARITY 2 study and the ongoing CLARITY EXTENSION study in patients with relapsing-remitting MS. Cladribine Tablets were recently approved in Australia and Russia as a treatment of relapsing-remitting MS, under the brand name Movectro(R), and are under regulatory review in other countries. Registration applications for Cladribine Tablets as a treatment for relapsing-remitting MS are supported by the results from the CLARITY study.
1 ORACLE MS: ORAl CLadribine in Early MS
2 CLARITY: CLAdRIbine Tablets treating MS orallY
ORACLE MS study design
The ORACLE MS study is a two-year (96-week), randomized, double-blind, placebo-controlled, international trial. It randomized 617 patients considered at risk of developing MS due to a recently experienced isolated demyelinating event (e.g. optic neuritis, myelopathy or brainstem syndrome) and having MRI brain scans consistent with early signs of MS. Study participants were randomized to one of three different treatment groups consisting of two different dose regimens of Cladribine Tablets or matching placebo tablets (1:1:1 ratio).
Patients will be treated for a period of two years (96 weeks), or up to the time when they experience a second attack leading to a diagnosis of clinically definite MS, in which case they would be offered open-label treatment with Rebif(R) 44 mcg three times a week for a 96-week maintenance treatment period. Patients who do not convert to clinically definite MS within the initial 96-week period of the study will be eligible to enroll in a 96-week long-term follow-up treatment period. These maintenance and long-term follow-up periods of the study are intended to assess the effect of early treatment with Cladribine Tablets on relapses and subsequent treatment response to disease-modifying therapy for relapsing-remitting MS and to evaluate the sustained effect of Cladribine Tablets in delaying the development of definite MS.
In the study, Cladribine Tablets are given in two (3.5 mg/kg total dose) or four (5.25 mg/kg total dose) treatment courses in the first year, with each course consisting of once daily administration for four to five consecutive days (depending on patient weight), which means study patients take Cladribine Tablets for only 8 to 20 days during the first year. In the second year, two treatment cycles are administered to both patient groups receiving Cladribine Tablets, meaning that patients take Cladribine Tablets for 8 to 10 days during the second year.
The primary endpoint of the ORACLE MS study is time to conversion to clinically definite MS, according to the Poser criteria, defined by either a second attack, or a sustained increase in EDSS. Other endpoints include time to conversion to MS according to the McDonald criteria (the main secondary endpoint), assessments of MRI brain scans, and disability progression.
About Cladribine Tablets
Merck Serono's oral formulation of cladribine (Cladribine Tablets) is an investigational treatment for patients with relapsing forms of multiple sclerosis (MS). Cladribine is a small molecule that may interfere with the behavior and the proliferation of certain white blood cells, particularly lymphocytes, which are thought to be involved in the pathological process of MS. Cladribine Tablets were approved in Russia in July 2010 and in Australia in September 2010 as a treatment of relapsing-remitting MS and are under regulatory review in other countries.
The clinical development program for Cladribine Tablets includes:
- The CLARITY (CLAdRIbine Tablets treating MS orallY) study and its extension: a two-year Phase III placebo-controlled trial designed to evaluate the efficacy and safety of Cladribine Tablets as a monotherapy in patients with relapsing-remitting MS and the CLARITY EXTENSION two-year Phase III study designed to provide data on the long-term safety and efficacy of extended administration of Cladribine Tablets for up to four years. - The ORACLE MS (ORAl CLadribine in Early MS) study: a two-year Phase III placebo-controlled trial designed to evaluate the efficacy and safety of Cladribine Tablets as a monotherapy in patients at risk of developing MS (patients who have experienced a first clinical event suggestive of MS). This trial was announced in September 2008. - The ONWARD (Oral Cladribine added oN to interferon beta-1a in patients With Active Relapsing Disease) study: a Phase II placebo-controlled trial designed primarily to evaluate the safety and tolerability of adding Cladribine Tablets treatment to patients with relapsing forms of MS, who have experienced breakthrough disease while on established interferon-beta therapy. This trial was announced in January 2007. - The PREMIERE (PRospective observational long-term safEty registry of Multiple sclerosis patIEnts who have participated in CladRibinE clinical trials) registry: an eight-year observational safety registry of patients who have participated in Cladribine Tablets clinical trials, designed to support the evaluation of the long-term safety of Cladribine Tablets in MS.
About multiple sclerosis
Multiple sclerosis (MS) is a chronic, inflammatory condition of the central nervous system and is the most common, non-traumatic, disabling neurological disease in young adults. It is estimated that approximately two million people have MS worldwide. While symptoms can vary, the most common symptoms of MS include blurred vision, numbness or tingling in the limbs and problems with strength and coordination. The relapsing forms of MS are the most common.
About Merck Serono
Merck Serono is the division for innovative prescription pharmaceuticals of Merck KGaA, Darmstadt, Germany, a global pharmaceutical and chemical company. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, manufactures and markets innovative small molecules and biopharmaceuticals to help patients with unmet medical needs. In the United States and Canada, EMD Serono operates through separately incorporated affiliates.
Merck Serono has leading brands serving patients with cancer (Erbitux(R), cetuximab), multiple sclerosis (Rebif(R), interferon beta-1a), infertility (Gonal-f(R), follitropin alfa), endocrine and metabolic disorders (Saizen(R) and Serostim(R), somatropin), (Kuvan(R), sapropterin dihydrochloride) as well as cardiometabolic diseases (Glucophage(R), metformin), (Concor(R), bisoprolol), (Euthyrox(R), levothyroxine). Not all products are available in all markets.
With an annual R&D expenditure of more than EUR 1 billion, Merck Serono is committed to growing its business in specialist-focused therapeutic areas including neurodegenerative diseases, oncology, fertility and endocrinology, as well as new areas potentially arising out of research and development in autoimmune and inflammatory diseases.
Merck is a global pharmaceutical and chemical company with total revenues of EUR 7.7 billion in 2009, a history that began in 1668, and a future shaped by approximately 40,000 (including Merck Millipore) employees in 64 countries. Its success is characterized by innovations from entrepreneurial employees. Merck's operating activities come under the umbrella of Merck KGaA, in which the Merck family holds an approximately 70% interest and free shareholders own the remaining approximately 30%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and has been an independent company ever since.
Merck Serono is a division of Merck.
SOURCE: Merck Serono
CONTACT: Merck Serono S.A. - Geneva: 9 Chemin des Mines, 1202 Genève,Suisse, Media relations, Tel: +41-22-414-36-00