Natalizumab is an alpha-4 integrin inhibitor that is designed to prevent migration of inflammatory cells from blood vessels to the site of inflammation. Elan Corporation plc and Biogen Inc. are collaborating on the development of natalizumab.
The study enrolled 244 moderate to severely active patients with Crohn's Disease (Crohn's Disease Activity Index ('CDAI') score 220-450), from 38 sites in 8 countries.
The data was reported on 23 May 2001 to the DDW meeting, held in Atlanta, Georgia, USA.
The patients were randomized to one of four treatment groups. These were: a single 3 mg/kg natalizumab infusion; two 3 mg/kg natalizumab infusions at a 4-week interval; two 6 mg/kg natalizumab infusions at a 4-week interval; or placebo.
|Proportion of patients achieving remission:|
3 mg/kg natalizumab: 46%
Patients were followed for 12 weeks following the first infusion and were assessed using the CDAI and changes in quality of life, as assessed by the Inflammatory Bowel Disease Questionnaire ('IBDQ').
A statistically significant difference in clinical response (decrease of more than 70 points in CDAI) was noted as early as Week 2 and was maintained through Week 12. The researchers observed a maximal response of 74% in the 3 mg/kg-dose group versus 38% in the placebo group.
Remission, defined as a CDAI score of less than 150, was achieved by 46% of patients in the 3 mg/kg dose group versus 27% in the placebo group.
There was also a statistically significant difference in the change from baseline IBDQ score in patients receiving two infusions of natalizumab as compared to those receiving placebo at both Week 6 and Week 12.
In this trial natalizumab was generally well tolerated. Data suggests that the most common adverse events reported were headache and abdominal pain. There were no notable differences among treatment groups in the number of patients reporting side-effects.
Phase III studies are expected later this year.
The study's lead investigator, Professor Paul Rutgeerts of the Department of Endoscopy, Universitaire Ziekenhuizen Leuven, Belgium, said, "Many existing therapies have problematic side-effects, or have questions concerning safety with long-term use; therefore, other therapies are needed to treat this disease."
"The Phase II data are exciting because they show, for the first time, that this novel humanized monoclonal antibody may provide an effective treatment to induce remission and maintenance of Crohn's Disease," he concluded.