The investigational agent NOE-105 has previously been found safe for treating adults with Tourette syndrome at 30-mg daily doses.
Noema Pharma announced a phase 2a dose ranging study of NOE-105, a phosphodiesterase 10A (PDE10A) inhibitor, for use in treating patients with Tourette syndrome. The Allevia trial (ACTRN12621000319875) is expected to report clinical data in the first half of 2022.
The multicenter, 12-week, prospective study is led by Noema Pharma, evaluating the safety and efficacy of NOE-105, one of several products in-licensed from Roche. Adult male patients with Tourette syndrome, aged 18 to 50 years, will be given a daily dose range of 5 mg to 15 mg of NOE-105 over the course of the trial. Doses are taken orally and may be upped by weekly increments of 2.5 mg, up to 15 mg, based on clinical evaluation and the absence of tolerability issues.
“This dose ranging study will help generate useful data to understand the efficacy and safety of NOE-105 in patients with Tourette syndrome,” George Garibaldi, MD, chief medical officer of Noema Pharma, said in a statement. “In a neuroimaging study using a PET tracer, the drug has shown a good penetration of the brain and a dose proportional target engagement. This study will further allow us to better understand the efficacy of NOE-105 in patients presenting with comorbidities associated with Tourette.”
Primary outcomes will be evaluated by the Tourette Syndrome Clinical Global Impression of Change (TS-CGI-C), with patients reporting symptoms as minimally improved, much improved, and very much improved. Secondary end points include a blood sample analysis, evaluation of electrocardiogram and vital signs, and the presence adverse events (AEs) and serious AEs. At week 12 or at the time of patient’s discontinuation, investigators will further identify change in tic symptom severity using the Yale Global Tic Severity Scale and change in severity of patient’s illness using the TS-CGI Severity scale.
NOE-105 has previously been found safe in adults at repeated doses of up to 30 mg each day. Treatment with NOE-105 modulates the dopamine-2 receptor as an inhibitor of PDE10A, an enzyme found in the mammalian striatum inhibitor, expressed in medium spiny neurons. Unlike antipsychotics, which are often used to treat patients with Tourette syndrome, NOE-105 is not associated with motor and metabolic adverse effects such as insulin resistance and type 2 diabetes.
A total of 10 participants are anticipated to be enrolled in the study. Exclusion criteria include current diagnosis of bipolar disorder, schizophrenia, and major depressive disorder (MDD); however, patients with MDD on stable treatment with antidepressants for more than 1 month are eligible. Participants may also be excluded due to secondary tic symptoms, accompanied by late-onset tics, Huntington chorea, neuroacanthocytosis, mental retardation, or autism; a history of severe traumatic brain injury or stroke; unstable medical conditions that may increase risk of AEs; uncontrolled seizure disorders; or cognitive-behavioral therapy, if started less than 8 weeks before the trial’s start.
According to experts, the treatment could generate life-changing effects for patients with Tourette syndrome, as treatment options are currently limited. “Tourette syndrome can be a devastating disease, significantly affecting patients’ confidence and ability to go about everyday tasks,” Andreas Hartmann, MD, Sorbonne University, Pitié-Salpêtrière Hospital, Paris, said in a statement. “There is a substantial unmet medical need because existing treatments have potentially limited benefits and significant drawbacks. The clinical development of NOE-105 offers a possibility to improve this treatment landscape and to bring a greater sense of normality back to patients’ lives.”
Hartmann will partner with principal investigators, Philip E. Mosely, BMBCh, PhD, Westly Medical Research Institute, Auchenflower, Australia; and Andrew Evans, MBBS, MD, FRACP, Royal Melbourne Hospital, Australia, to evaluate safety and efficacy of NOE-105. Noema Pharma is also in phase 2 of NOE-101, a negative allosteric modulator of mGluR5, for treatment of seizures associated with tuberous sclerosis complex and management of pain associated with trigeminal neuralgia.