AZTherapies Completes Enrollment for ALZT-OP1 Trial for Early Alzheimer’s

AZTherapies has completed enrollment for its Phase 3 COGNITE trial, testing the safety and efficacy of its investigational ALZT-OP1 for the treatment of early Alzheimer’s disease (AD).

A total of 620 participants were enrolled following the screening of 1,800 patients, the company said.

“With the COGNITE trial now fully enrolled, we are one step closer to providing Alzheimer’s patients with new hope for a treatment and look forward to completing the trial in late 2020,” David R. Elmaleh, PhD, founder, CEO, and chairman of AZTherapies, said in a press release.

In Alzheimer’s disease, the activation of brain immune cells such as astrocytes and microglia release excessive amounts of inflammation-causing molecules. These molecules, known as cytokines, can damage nerve cells. The accumulation of amyloid beta plaques — toxic clumps of amyloid beta protein in the brain, thought to underlie Alzheimer’s — also are known to trigger this neuroinflammatory process.

ALZT-OP1 is a two-part therapy that consists of a dry-powder inhaler containing cromolyn (designated ALZT-OP1a), and an oral pill containing ibuprofen (designated ALZT-OP1b).

Cromolyn is an FDA-approved therapy to treat asthma, but it was shown to halt the formation of toxic amyloid plaques. The therapy also has an anti-inflammatory effect, which is the main function of ibuprofen, the second agent in ALZT-OP1. Ibuprofen is a non-steroidal medication, commonly used as a painkiller, that slows the inflammatory process in Alzheimer’s.

“ALZT-OP1 uses a novel multi-modal approach that includes attacking the neuroinflammation that leads to neuronal death,” Elmaleh said.

“By attempting to enhance the brain’s microglial immune cells’ neuroprotective activity and inhibit pro-inflammatory cytokine production, we aim to halt or slow the progression of Alzheimer’s disease in its early stages. ALZT-OP1 is a proprietary combination of two previously approved small molecules that have been re-engineered to provide a daily dose to suppress the brain’s neuroinflammatory response,” Emaleh added.

The COGNITE trial (NCT02547818), underway in 90 clinical sites in the U.S., Canada, Australia, and certain countries in Europe, has now enrolled 620 patients, ages 55 to 79, with early Alzheimer’s disease.

Participants were identified using cognition, function, and biomarker levels in the cerebrospinal fluid (CSF) — the liquid that surrounds the brain and spinal cord. The screening ensured all the participants were in the early stages of Alzheimer’s.

“I am encouraged by the continued progress in this clinical trial,” said Martin Farlow, MD, a member of the AZTherapies Scientific Advisory Board, and a practicing neurologist.

“This trial encompasses a number of unique features, including the narrow age spread of patients, the early stage of disease, and the battery of cognition, function, and the CSF measures included, which may shed light on disease progression,” added Farlow, also professor emeritus of neurology at Indiana University School of Medicine.

Participants will be random assigned to one of four treatment groups: inhaled cromolyn capsules plus oral placebo tablets; combo therapy of inhaled cromolyn together with oral ibuprofen; inhaled placebo capsules and oral ibuprofen tablets; or inhaled placebo capsules plus oral placebo tablets.

The study’s main objective, or endpoint, is to assess the efficacy of ALZT-OP1, measured by changes after 72 weeks in the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb), a scale for assessing dementia severity.

The trial is being conducted under a special protocol assessment (SPA) agreement with the FDA.

“A positive outcome in this study could be a meaningful breakthrough in the treatment of early Alzheimer’s disease, validating the role that neuroinflammation plays in neurodegeneration and positioning ALZT-OP1 as a promising new option for the millions of people living with Alzheimer’s disease,” Farlow said.