Last Patient Finishes ALZT-OP1 Combo Therapy Trial; Results Expected Early 2021

The last participant has completed all predefined assessments in the Phase 3 COGNITE clinical trial, which is assessing the safety and effectiveness of AZTherapies’ treatment candidate ALZT-OP1 for people with early Alzheimer’s disease.

The trial’s top-line results are expected in the first months of 2021. The biopharmaceutical company hopes its investigational therapy will be found to slow or even stop the progression of Alzheimer’s.

“We will soon begin data analysis, bringing us one step closer to validating our hypothesis that targeting neuroinflammation could be the key to modifying disease progression — stopping or slowing the advance of early stage Alzheimer’s disease,” David R. Elmaleh, PhD, AZTherapies’ scientific founder, executive chairman, and chief scientific officer, said in a press release.

“Notably, the COGNITE trial also includes a landmark cerebrospinal fluid [CSF] biomarker component that should allow for future exploration of correlations between biomarkers and clinical response,” Elmaleh added. Of note, the CSF is the fluid that surrounds the brain and spinal cord.

ALZT-OP1 is a proprietary combination of two previously approved small molecules that have been re-engineered and optimized to reach the brain and provide a daily dose that could potentially suppress the neuroinflammation that leads to neuronal death in Alzheimer’s patients.

Designed to be a convenient and easy-to-use inhaled and oral delivery kit for once-daily home use, ALZT-OP1 consists of a dry-powder inhaler containing cromolyn (designated ALZT-OP1a) and oral pills containing ibuprofen (designated ALZT-OP1b).

Preclinical studies have shown that cromolyn, used to treat asthma, can halt the formation of toxic amyloid-beta clumps — one of Alzheimer’s hallmarks that contributes to neuroinflammation — and reduce the release of pro-inflammatory molecules.

Alone and in combination with ibuprofen — an anti-inflammatory medication commonly used as a painkiller — cromolyn was shown, in a mouse model of Alzheimer’s, to also reduce amyloid-beta clumps and promote a shift in the brain’s microglial immune cells from a pro-inflammatory state to a neuroprotective state.

As such, ALZT-OP1’s multi-modal approach is expected to lower neuroinflammation and potentially slow or halt disease progression in people with early stage Alzheimer’s.

The COGNITE trial (NCT02547818) was designed to evaluate ALZT-OP1’s safety and effectiveness in people, ages 55 to 79, with early Alzheimer’s disease. A total of 620 patients were recruited at more than 100 clinical sites clinical sites across the U.S., Canada, Australia, and Europe.

At study entry, the patients’ disease stage was assessed with the Clinical Dementia Rating scale — a validated measure of dementia severity. That scale also was used to rate the levels of key CSF biomarkers.

The participants were randomly assigned to receive one of four combination treatments: ALZT-OP1 (ALZT-OP1a and ALZT-OP1b), ALZT-OP1a with an oral placebo, inhaled placebo with ALZT-OP1b, or both inhaled and oral placebos. Treatment was given for 72 weeks (about 17 months).

COGNITE’s main goal is to assess changes in the Clinical Dementia Rating Scale Sum of Boxes from the study’s start to end, or from zero-to-72 weeks of treatment.

The trial is being conducted under a special protocol assessment agreement with the U.S. Food and Drug Administration, and if it provides positive findings, the company plans to file for ALZT-OP1’s regulatory approval in the U.S.

“As we eagerly anticipate the results, we would like to take this opportunity to thank all of our investigators, our clinical teams, and, most importantly, the patients and families who participated in this important clinical trial,” Elmaleh said.