Phase 2 Trial of XPro1595 in Patients With Inflammation Being Planned
A partnership agreement will allow INmune Bio to continue using biomarker imaging technology by Imeka in future clinical trials evaluating XPro1595, the company’s investigational therapy for Alzheimer’s disease.
INmune Bio is planning to initiate a Phase 2 study of XPro1595 in Alzheimer’s patients this year, it stated in a press release.
The agreement follows early evidence from its Phase 1b clinical trial (NCT03943264), which took place in Australia, that XPro1595’s use lowered white matter free water, a biomarker of neuroinflammation, in adults with mild to moderate Alzheimer’s disease who showed signs of inflammation.
Results also indicated that XPro1595 increased the integrity of axons, the nerve cell projections that transmit information (electrical impulses), in specific regions of patients’ brains as measured by apparent fiber density.
Both markers of treatment benefit to the brain’s white matter were evaluated using Imeka’s non-invasive MRI imaging technology. (White matter is the brain tissue made up of nerve cell projections, known as axons or fibers that connect different brain regions. Their color comes from the myelin coating sheath, the fatty substance that wraps around and protects axons.)
The technology evaluates three parameters of white matter — apparent fiber density (AFD), extracellular water fraction (white matter free water), and tissue radial diffusivity (tRD) — allowing researchers and clinicians to determine the degree of myelin and axonal loss, as well as neuroinflammation.
“Traditional approaches to the search for new treatments have been hampered by the nature of the brain — the brain is a complex environment that requires advanced modeling. Imeka’s proprietary biomarker technology provides clarity into white matter and enables researchers to understand if, how, and precisely where in the brain their drugs are working,” said Jean-René Bélanger, Imeka’s chief executive officer.
XPro1595 is designed to lower inflammation in the brain by selectively blocking an inflammatory cell signaling molecule, called soluble tumor necrosis factor (sTNF), which has been implicated in Alzheimer’s progression. It is reported to do so without affecting trans-membrane TNF or TNF receptors present on cells’ membranes, in contrast to other TNF inhibitors.
Patients in the open-label Phase 1b study received one of two doses of XPro1595 — a low (0.3 mg/kg) or high (1.0 mg/kg) dose — injected subcutaneously (under the skin) once a week for 12 weeks.
A main study aim was to identify those patients most likely to benefit from XPro1595, while evaluating treatment safety.
The proposed Phase 2 trial intends to enroll up to 168 people with mild Alzheimer’s and markers of neuroinflammation, who will be randomized to treatment with XPro1595 at 1.0 mg/kg or to a placebo for about six months, INmune Bio announced in a July release. Changes in measures of cognition will be a primary study goal.
People who complete the Phase 2 study will have the option of continuing or starting on this treatment in its one-year and open-label extension.
In the Phase 1b study, “we were able to demonstrate that XPro1595 neutralizes soluble TNF and decreases biomarkers of neuroinflammation across multiple measures and assays in Alzheimer’s patients,” Raymond J, Tesi, MD, chief executive officer of INmune Bio said in the release. “The data suggest that decreasing neuroinflammation results in significant improvements in biomarkers of neurodegeneration and synaptic function.”
Findings also “support the use of white matter free-water as a neuroinflammatory biomarker and AFD as a neurodegeneration biomarker for treatment response,” Tesi added. “We look forward to initiating a blinded, randomized Phase 2 study by the end of this year as we continue to develop and advance novel therapeutics targeting dysfunction of the innate immune system.”