NCT05514340

Assess Safety and Efficacy of Sovateltide in Hypoxic-ischemic Encephalopathy

A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase-II Trial to Assess Safety, and Efficacy of Sovateltide in the Treatment of Hypoxic-ischemic Encephalopathy in Neonates

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Pharmazz, Inc. · Industry
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

Sovateltide (PMZ-1620; IRL-1620) is targeted to be used as a "Treatment for hypoxic-ischemic encephalopathy in neonates," which is a life-threatening condition. Sovateltide augments neuronal progenitor cell differentiation and better mitochondrial morphology and biogenesis to activate a regenerative response in the central nervous system. The only treatment for HIE is therapeutic hypothermia with limited success, and studies indicate that sovateltide may be beneficial in these patients.

Detailed description

Neonatal encephalopathy due to perinatal asphyxia is known as hypoxic-ischemic encephalopathy (HIE). HIE is a serious neurological complication affecting premature and full-term neonates, resulting from oxygen deprivation and reduced blood flow to the neonatal brain, leading to neuronal and white matter injury. Currently, no well-established therapies are considered effective for neonatal HIE. The standard of care at present includes supportive management to maintain cerebral perfusion, metabolic balance, and seizure detection and treatment. Currently, the only neuroprotective treatment for HIE is therapeutic hypothermia. However, improvement in patient outcomes following therapy has been moderate, with only 1 in 6 infants benefitting from therapeutic hypothermia. Additionally, therapeutic hypothermia is time-sensitive, having a narrow therapeutic window wherein therapy must be initiated within 6 hours of delivery to be effective. Timely initiation is also restricted to those neonatal units having adequate equipment and trained staff for therapeutic hypothermia. Death or disability is reported to occur in 55% of infants receiving therapeutic hypothermia. To the best of our knowledge, there is no pharmacotherapy available for the treatment of HIE. Hence, there is a significant unmet medical need. ETB receptors located widely throughout the CNS are a necessary component of the developing nervous system and also promote neurorestorative processes involving neurogenesis and synaptogenesis. There was an increased expression of neural progenitor markers, NeuroD1 and Double Cortin, and neural markers for mature neurons, NeuN was observed in the sovateltide group compared to vehicle. In addition, Sovateltide increased the expression of presynaptic markers (synapsin1 and synaptophysin) and post-synaptic marker (Postsynaptic Density-95) compared to vehicle. Our results suggest that sovateltide treatment helps recruit and differentiate neural progenitor cells and augments synaptogenesis and endogenous neurorestorative processes. Sovateltide is a synthetic analog of ET-1 synthesized in 1992 and is a highly specific ETB receptor agonist. We and others have conducted studies to determine the effects of sovateltide upon its interaction with neural ETB receptors and have found that it enhances angiogenesis and neurogenesis and promotes repair and regeneration. This is indicated by neuronal cell proliferation, alleviation of oxidative stress, improvement of neurological and motor functions, and increase in anti-apoptotic markers. In our preclinical study, sovateltide was shown to have neuroprotective effects by promoting repair and regeneration in the brain in a neonatal rat model of HIE. The study showed that sovateltide treatment alone or in combination with hypothermia significantly (p\<0.01) increased ETB receptor expression compared to vehicle-treated rat pups. In addition, enhanced VEGF and NGF expression were observed in rat pups treated with Sovateltide alone or in combination with hypothermia compared to vehicle-treated rat pups (p\<0.0001, p\<0.0001). Sovateltide alone and in combination with hypothermia also demonstrated a significantly reduced number of apoptotic cells compared to the control group. Furthermore, oxidative stress markers, including malondialdehyde, reduced glutathione, and superoxide dismutase was, significantly improved (p\<0.0001, p\<0.0001, p\<0.0001) in those rat pups treated with sovateltide. Sovateltide was safe and well-tolerated in a Phase I trial (CTRI/2016/11/007509) in healthy human volunteers. In addition, we conducted human studies in patients with cerebral ischemic stroke (NCT04046484, CTRI/2017/11/010654; NCT04047563, CTRI/2019/09/021373), Alzheimer's disease (NCT04052737, CTRI/2017/12/016394), and acute spinal cord injury (NCT04054414, CTRI/2018/12/016667) patients. In summary, about 300 patients have been treated with sovateltide, and no drug-related adverse event has been reported to date. We plan to conduct a phase II clinical study to evaluate the safety and efficacy of sovateltide therapy along with supportive management in neonates with perinatal asphyxia (HIE). The dose of sovateltide proposed for this phase II study is 0.3µg/kg same as used in the phase II study in ischemic stroke.

Conditions

• Hypoxic-Ischemic Encephalopathy
• Neonatal Asphyxia
• Neonatal Encephalopathy

Interventions

Type	Name	Description
DRUG	Normal Saline along with standard treatment	Sovateltide is an endothelin-B receptor agonist. It has the potential to be a first-in-class neuronal progenitor cell therapeutics that is likely to promote quicker recovery and improve neurological outcome in hypoxic-ischemic encephalopathy patients. In this arm normal saline along with standard treatment will be given for active comparison.
DRUG	Sovateltide along with standard treatment	Sovateltide is an endothelin-B receptor agonist. It has the potential to be a first-in-class neuronal progenitor cell therapeutics that is likely to promote quicker recovery and improve neurological outcome in hypoxic-ischemic encephalopathy patients. In this arm sovateltide along with standard treatment will be given for active comparison.

Timeline

• Start date: 2023-09-06
• Primary completion: 2026-11-01
• Completion: 2026-12-01
• First posted: 2022-08-24
• Last updated: 2025-12-31

Locations

4 sites across 1 country: India