Safety and Efficacy of NP-120 (Ifenprodil) for the Treatment of Confirmed COVID-19 Infected Hospitalized Patients
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|ClinicalTrials.gov Identifier: NCT04382924|
Recruitment Status : Not yet recruiting
First Posted : May 11, 2020
Last Update Posted : May 11, 2020
The purpose of this adaptive trial is to determine the clinical efficacy of Ifenprodil in the treatment of patients infected with COVID-19. This Protocol is largely based on the recommendations of the WHO R&D Blueprint Clinical Trials Expert Group COVID-19 Therapeutic Trial Synopsis, and associated Master Protocol.
The choice of the primary outcome measure will be determined by a pilot study of the first 100 subjects. Subject clinical status (on a 7-point ordinal scale) at day 15 in treatment versus the control group is the default primary endpoint.
|Condition or disease||Intervention/treatment||Phase|
|COVID||Drug: NP-120 (Ifenprodil)||Phase 2 Phase 3|
NP-120 (Ifenprodil) is an N-methyl-D-Aspartate (NDMA) inhibitor that is specific for the NR2B subunit of the NMDA Receptor. The NMDA receptor, and specifically the NR2B subunit, is involved in glutamate signaling, and is expressed on both neutrophils and T cells. In the case of neutrophils, activation of the NMDA receptor can (1) result in expression of CD11b which targets neutrophils via ICAM-1 to areas of inflammation, and (2) trigger the autocrine release of glutamate. In the case of T-cells, activation of T cells via glutamate can cause (1) T cell proliferation and, (2) the release of cytokines. The activation of T cells and cytokine release can be blocked in vitro by the addition of Ifenprodil. As such it could be a potent anti-inflammatory agent.
Ifenprodil was discovered by a genome wide RNAi assay to uncover gene targets associated with cytoprotective activity against highly pathogenic H5N1 influenza, specifically by preserving cell viability in vitro. When tested in a murine model of H5N1, the drug at clinically relevant doses: (1) improved survivability from 0% at day 6 to 40% day 14 post-infection, (2) the drug significantly reduced edema and lung injury score and (3) reduced infiltrating T cells, neutrophils and NK cells and attenuated the 'cytokine storm'. The mortality rate of H5N1 in humans is >50%, whereas the mortality rate of COVID-19 infected patients is < 5%, and both viruses cause acute lung injury and share similar pulmonary pathologies. NP-120 has also been shown to mediate anti-inflammatory responses and reduce pulmonary fibrosis in a murine model of idiopathic pulmonary fibrosis, a complication which can occur after a respiratory virus infection.
Based on the fact that H5N1 has a significantly higher mortality rate than COVID-19 but still shares similar lung pathologies, Algernon Pharmaceuticals believes Ifenprodil could reduce lung injury associated with COVID-19 infection, thereby improving lung function and accelerating patient recovery.
The purpose of this adaptive Phase 2b/3 trial is to determine the safety and efficacy of NP-120 in the treatment of COVID-19 infection.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||462 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Open Label Phase 2b/3 Study of the Safety and Efficacy of NP-120 (Ifenprodil) for the Treatment of Confirmed COVID-19 Infected Hospitalized Patients|
|Estimated Study Start Date :||July 2020|
|Estimated Primary Completion Date :||January 2022|
|Estimated Study Completion Date :||February 2022|
Experimental: Treatment Arm
NP-120 (Ifenprodil) 20 mg TID + Standard of Care
Drug: NP-120 (Ifenprodil)
Ifenprodil, 20 mg TID
No Intervention: Control Arm
Standard of Care only
- Patient clinical status (on the WHO 7-point ordinal scale) at day 15 in IP versus SOC control group patients: [ Time Frame: Day 15 ]
- Not hospitalized, no limitations on activities
- Not hospitalized, limitation on activities
- Hospitalized, not requiring supplemental oxygen
- Hospitalized, requiring supplemental oxygen
- Hospitalized, on non-invasive ventilation or high flow oxygen devices
- Hospitalized, on invasive mechanical ventilation or ECMO
- Status on an ordinal scale assessed daily while hospitalized and on days 15 and 28 in IP versus control group patients [ Time Frame: Days 1 through 28 ]
- NEWS assessed days 3, 5, 8 ,11 daily while hospitalized and on days 15 and 29 in IP versus control group patients [ Time Frame: Days 3, 5, 8, 11, 25, 29 ]
- Rate of mechanical ventilation in IP versus control group patients [ Time Frame: Day 15, 28 ]
- Duration of mechanical ventilation (if applicable) in IP versus control group patients [ Time Frame: Day 15, 28 ]
- Duration of supplemental oxygen in IP versus control group patients [ Time Frame: Day 15, 28 ]
- Time to return to room pressure (SpO2 > 94%) on room air [ Time Frame: Day 15, 28 ]
- Duration in ICU (if applicable) in IP versus control group patients [ Time Frame: Day 15, 28 ]
- Rate of Mortality in IP versus control group patients [ Time Frame: Day 15, 28 ]
- Duration of hospitalization in IP versus control group patients [ Time Frame: Day 15, 28 ]
- Time to discharge in IP versus control group patients [ Time Frame: Day 15, 28 ]
- Effect on the rate of change of partial pressure of oxygen (PaO2) and PaO2/FiO2 ratio taken at baseline and measured once daily up to 2 weeks of treatment in IP versus control group patients [ Time Frame: Up to day 15, day 28 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04382924
|Contact: Nancy Stewart, Ph.D.||firstname.lastname@example.org|
|Contact: Mark Williams, Ph.D.||email@example.com|