NNZ-2591 Phase 2 trial of children with PWS is recruiting in US
Study expects to enroll up to 20 children at sites across the country
Neuren Pharmaceuticals has opened the first site for a U.S.-based Phase 2 clinical trial of its investigational therapy NNZ-2591 in children with Prader-Willi syndrome (PWS).
“The Neuren team is very excited to be working with the community to complete this important first study of NNZ-2591 in young children with Prader-Willi syndrome,” Neuren’s CEO, Jon Pilcher, said in a company press release. “We are eager to assess the potential impact of NNZ-2591, having observed highly encouraging effects in [a PWS] pre-clinical model.”
The Phase 2 trial, called PWS-001 (NCT05879614), expects to enroll up to 20 children, ages 4-12, at sites across the U.S. The location of the first site hasn’t been disclosed. The study will examine NNZ-2591’s safety, tolerability, pharmacological properties, and preliminary effectiveness over 13 weeks (about three months).
The site’s opening comes about five months after Neuron was given the OK from the U.S. Food and Drug Administration to launch a trial.
The company expects the Phase 2 trial data will prompt a Phase 3 trial whose findings, if positive, would support an application for the therapy’s approval in the U.S.
“In parallel with conducting the Phase 2 trial, Neuren is executing the additional development work required to be ready for Phase 3 development,” the release stated.
Results of preclinical, Phase 1 studies of NNZ-2591
NNZ-2591 is a lab-made version of the cyclic glycine proline protein. This naturally occurring protein regulates the signaling of insulin-like growth factor 1 (IGF-1), a hormone involved in metabolism, growth, and brain development that’s deficient in PWS.
The therapy, which can reach the brain, is intended to normalize IGF-1 in the brain, reduce inflammation, and restore normal communication between brain cells. It’s also designed to enhance IGF-1 signaling in impaired cells, without affecting healthy cells, according to Neuren.
In preclinical studies, six weeks of NNZ-2591 normalized all behavioral problems in a mouse model of PWS, including cognitive impairment, anxiety, social issues, and low physical activity.
High-dose treatment also normalized IGF-1 levels and fat mass, while a lower dose led to a “partial reversion.” It had no effect on healthy mice.
In a previous Phase 1 clinical trial (NCT04379869) of 28 healthy volunteers, single and multiple doses of NNZ-2591 were found to be safe and tolerated well, and showed good bloodstream absorption and brain access.
In Phase 2, participants will be observed for at least four weeks to establish pretreatment characteristics, after which they’ll receive NNZ-2591 as an oral liquid twice daily, with two increases up to the target dose (50 mg/mL) during the first six weeks.
After 13 weeks at the target dose, the children will complete a follow-up assessment two weeks later.
The study will include two age groups and the safety and tolerability data in the older group will be independently reviewed before the younger patients are dosed.
Exploratory efficacy measures, as examined by caregivers and clinicians, will include the Clinical Global Impression Scale & Domain-Overall Improvement Score, the Clinical Global Impression Scale-Severity Overall Score, and the Caregiver Global Impression-Change Score. A number of behavioral tests will also be applied.
The company is also investigating NNZ-2591 for other serious neurological disorders of early childhood that feature impaired nerve cell communication. These include Angelman syndrome, Phelan-McDermid, and Pitt Hopkins syndromes. Clinical trials for these indications are underway.
According to Neuren, the FDA has granted orphan drug status to NNZ-2591 for all four indications. The designation is intended to speed a therapy’s clinical development and regulatory review.
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