The first patient has been dosed in a Phase 2a clinical trial evaluating the safety and effectiveness of ALZT-OP1a, a dry-powder inhaled formulation of cromolyn, in people with mild-to-moderate amyotrophic lateral sclerosis (ALS).
The trial (NCT04428775) is recruiting up to 80 patients, ages 18–75, who have been diagnosed in the prior two years, and have non-bulbar ALS (their first symptoms were not problems in speech or swallowing).
It will enroll participants at up to 20 centers across the U.S., with recruitment already underway at the Wake Forest School of Medicine, in North Carolina. More information about contacts and eligibility is available here.
The trial builds on prior preclinical research, conducted in the labs of Ghazaleh Sadri-Vikili, PhD, and Rudolph Tanzi, PhD, at Massachusetts General Hospital, where cromolyn was tested as a potential ALS treatment in an animal model of disease.
Cromolyn, ALZT-OP1a’s active ingredient, is an anti-inflammatory medication approved by the U.S. Food and Drug Administration (FDA) to treat mastocytosis, a condition associated with an abnormally high amount of certain immune cells.
In the precinical study, cromolyn delayed disease onset and progression, and helped ease motor deficits. It also reduced the levels of inflammatory molecules in the blood and spinal cord, and reduced immune cell activation, ultimately preventing the loss of motor neurons — the hallmark of ALS.
“In our pre-clinical evaluations, ALZT-OP1a demonstrated the ability to delay disease onset and progress, reduce motor deficits, and reduce pro-inflammatory cytokine/chemokine levels in the spinal cord and plasma of mice. I will be following the progress of this trial with great interest,” Tanzi, co-director of the MassGeneral Institute for Neurodegenerative Disease and chair of the AZTherapies scientific advisory board, said in a press release.
“We have been able to progress this program rapidly from bench to bedside based on comprehensive pre-clinical work and are optimistic that we will see clear safety and efficacy signals from this clinical trial. We believe this is not only a significant step forward for us, but, more importantly, for the many ALS patients with so few treatment options,” said David R. Elmaleh, PhD, founder, CEO and chairman of AZTherapies.
While preclinical studies investigated cromolyn that was delivered into the abdominal cavity, AZTherapies developed ALZT-OP1a, a cromolyn inhaled formulation that increases the amount of drug that reaches the central nervous system.
The open-label trial will assign patients randomly to a low dose (17.1 mg, twice a day) or high dose (34.2 mg twice daily) of ALZT-OP, administered via inhalation for 12 weeks.
The trial’s main goal is to assess the effect of ALZT-OP1a on biomarkers of ALS in the blood. Researchers also will investigate changes in disease severity and lung function, as well as the treatment’s safety and tolerability.
The study also will seek to determine the optimal dose of ALZT-OP1a to be used in future ALS clinical studies.
“We are excited to be participating in this trial and giving hope to ALS patients with a potential new treatment,” said James Caress, MD, director of the Wake Forest Health Sciences ALS Center, and the trial’s lead investigator.
“As a cytokine release modifier, we believe ALZT-OP1a could slow the development of this progressive neurodegenerative disease, which affects nerve cells in the brain and spinal cord resulting in loss of motor function. Controlling neuroinflammation is an important piece in the ALS treatment puzzle and I am hopeful that the broad spectrum of anti-inflammation activity expected from ALZT-OP1a administration will prove to be of benefit to my patients,” he said.
In addition to ALS, AZTherapies is testing ALZT-OP1a as part of a combination therapy for the treatment of early stage Alzheimer’s disease. A Phase 3 trial, called COGNITE (NCT02547818) is ongoing in the U.S., Australia, Canada, and Europe.
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