Ocrevus Phase 3 Trial Will Explore How Treatment Works by Viewing Changes in Spinal Fluid
Already an approved treatment for relapsing and primary progressive multiple sclerosis (MS), Ocrevus (ocrelizumab) is still undergoing scrutiny in several clinical trials. Most focus on the drug’s effects in specific patient groups, but one study aims to advance understanding of how Ocrevus works to harness disease.
To do so, the open-label Phase 3 trial (NCT02688985) will analyze participants’ cerebrospinal fluid, which bathes the brain and spinal cord.
Aiming to recruit 104 people with both relapsing and primary progressive disease — across 19 locations in North America, Germany, and Sweden — the study is open both to those new to disease-modifying treatment and those previously treated with interferons or Copaxone (glatiramer acetate).
Patients taking other therapies will need to stop treatment before starting Ocrevus infusions.
As in other Ocrevus trials, patients will be treated according to the drug’s prescription label. This means that the first 600-mg dose will be split into two infusions, two weeks apart. Two additional infusions, each 600-mg, will be given on weeks 24 and 48.
Researchers will — for the first time — analyze levels of a factor called Neurofilament Light (NFL), as well as CD19+ B-cells and CD3+ T-cells, in the spinal fluid of Ocrevus-treated participants.
Changes in the fluid levels of these biomarkers will be the trial’s primary outcome measure, bringing new insights into how Ocrevus impacts MS disease processes.
For a disease involving the central nervous system, such as MS, measures of various factors in the blood do not necessarily mirror processes taking place in the brain. By analyzing factors in the cerebrospinal fluid, researchers may be better able to assess what is going on in the brain.
“This is a hypothesis-generating study to elucidate the effect of Ocrevus on biomarkers of inflammation and neurodegeneration in the CSF [cerebrospinal fluid] and peripheral blood of patients with relapsing MS and primary progressive MS, in correlation with clinical and MRI [magnetic resonance imaging] outcome measures,” Hideki Garren, Genentech’s Group Medical Director of Ocrevus, told Multiple Sclerosis News Today when asked about this company-supported trial.
But what will the factors under scrutiny tell researchers about MS disease processes and Ocrevus’ effects?
“Specifically, NFL is a marker of axonal injury,” Garren said. “And the aim of the study is to assess the potential impact of Ocrevus on this process, as well as on the inflammation,” he added, referring to measurements of B- and T-cells, which are immune system components.
Genentech scientists, in an earlier interview, said they believe that Ocrevus, through its interaction with B-cells, also has an impact on T-cells. Measuring T-cell changes in the brain can, for this reason, deepen understanding of a treatment like Ocrevus, which primarily acts to deplete CD20-type B-cells.
The study will also look for the presence of anti-drug antibodies, which have the potential to prevent the treatment from doing its job. Other secondary measures include the concentration of Ocrevus in patients’ blood and spinal fluid.
As in the other trials, a safety component is included. Researchers will follow patients for up to 3.5 years to record any adverse side effects.
Spinal fluid sampling
All patients will have two spinal taps so researchers can sample cerebrospinal fluid, in addition to other types of testing.
Unfortunately, a spinal tap is not as straightforward as a blood test. About one-fourth of people who have a spinal tap typically develop a severe headache, accompanied by dizziness, nausea, and vomiting, although steps are taken to prevent or ease these reactions.
Patients will be split into five groups. Three groups of relapsing patients will receive identical treatment, but will be given spinal taps at different times. All will be sampled before treatment starts, and again either at week 12, 24, or 52.
The fourth group of relapsing patients will start Ocrevus treatment with a 12-week delay. In this group, researchers will collect spinal fluid at the start of the delay period, and again just before patients receive their first Ocrevus dose.
The fifth group, composed of primary progressive MS patients, will be given a spinal tap before the first dose and again at 52 weeks, after the last Ocrevus infusion.
The study is expected to be completed by September 2018.
Genentech is currently recruiting MS patients for this clinical trial at all locations. For more information, please visit this link.