COVIDPhase 2/3NCT04382924
Safety and Efficacy of NP-120 (Ifenprodil) for the Treatment of Hospitalized Patient With Confirmed COVID-19 Disease
A Phase 2/3 study testing NP-120 (Ifenprodil) in people with COVID, run by Algernon Pharmaceuticals at 10 sites in 4 countries.
Trial summary
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 World Health Organization (WHO) R\&D Blueprint Clinical Trials Expert Group COVID-19 Therapeutic Trial Synopsis, and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID
- What is being tested?
- NP-120 (Ifenprodil)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 168 participants
- Where
- 10 sitesin 4 countries
- Study dates
- 5 Aug 2020to 26 Jan 2021
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female subjects aged ≥18 years of age
- Confirmed coronavirus infection
- Positive real-time fluorescence polymerase chain reaction of the patient's respiratory or blood specimens for COVID-19 nucleic acid
- Viral gene sequences in respiratory or blood specimens that are highly homologous to COVID-19
- Any other diagnostic test accepted by local regulatory authorities
- Must be hospitalized and requiring supplemental oxygen, or on non-invasive ventilation or high flow oxygen devices (Score of 4 or 5 on WHO Ordinal Clinical Scale)
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- Female subjects of childbearing potential who are sexually active with a non-sterilized male partner must use at least 1 highly effective method of contraception (e.g. oral contraceptives, intrauterine device, diaphragm plus spermicide) from the time of screening and must agree to continue using such precautions for 90 days after the final dose of study drug(s)
- Non-sterilized males who are sexually active with a female partner of childbearing potential must use condom plus spermicide from day 1 through 90 days after receipt of the last dose of study drug(s)
- Subjects (or reasonable legal designate) must have the capacity to understand, sign and date a written, informed consent form and any required authorization prior to initiation of any study procedures
Who cannot join
- Patients with vasodilatory shock, orthostatic hypotension, hypotension, or tachycardia at screening/baseline
- Patients experiencing cerebral hemorrhage or cerebral infarction at baseline
- ALT/AST > 5 times the upper limit of normal; Child-Pugh Score 10 to 15
- Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR < 30)
- Patients on mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
- Patients taking droxidopa
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- Pregnant and lactating women and those planning to get pregnant
- Known or suspected allergy to the trial drug or the relevant drugs given in the trial
- Presence of other disease that may interfere with testing procedures or in the judgement of the Investigator may interfere with trial participation or may put the patient at risk when participating in this trial
- Know inability of patient to comply with the protocol for the duration of the study
- Involvement in a clinical research study within 4 weeks prior to screening and/or prior enrollment in the study or plan to participate in another interventional clinical trial during the study period. Participation in observational registry studies is permitted.
Trial locations and contacts
10 sites in 4 countries.
10 sites in 4 countries
United States4 sites
Affinity Health - Loretto Hospital
Chicago, Illinois, 60644
Westchester Research Center
Miami, Florida, 33155
Heartland Regional Medical Center
Saint Joseph, Missouri, 64507
Promedica Health: Toledo Hospital and BayPark Hospital
Toledo, Ohio, 43606
Philippines3 sites
Makati Medical Center
Manila
Philippine General Hospital
Manila
Lung Center of the Philippines
Quezon City
Australia2 sites
Royal Melbourne Hospital
Parkville, Victoria, 3050
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
About this study
Official title: A Randomized Open Label Phase 2b/3 Study of the Safety and Efficacy of NP-120 (Ifenprodil) for the Treatment of Hospitalized Patient With Confirmed COVID-19 Disease
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 World Health Organization (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 150 subjects. Subject clinical status (on a 7-point ordinal scale) at day 15 in treatment versus the control group is the default primary endpoint.
Read the detailed description
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 Phase 2b/3 trial is to determine the safety and efficacy of NP-120 in the treatment of COVID-19 infection.
- Conditions
- COVID
- Being tested
- NP-120 (Ifenprodil)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NP-120 (Ifenprodil)Drug
Ifenprodil, 20 mg TID Ifenprodil, 40 mg TID
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm A | Experimental | NP-120 (Ifenprodil) 20 mg TID + Standard of Care Receives: Drug: NP-120 (Ifenprodil) |
| Control Arm | No intervention | Standard of Care only |
| Treatment Arm B | Experimental | NP-120 (Ifenprodil) 40 mg TID + Standard of Care Receives: Drug: NP-120 (Ifenprodil) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patient Clinical Status (on the WHO 7-point Ordinal Scale) at Day 15 in IP Versus SOC Control Group Patients:
- 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
- Death
Measured: Day 15
Secondary outcomes (11)
Status on an Ordinal Scale Assessed Daily While Hospitalized and on Days 15 and 28 in IP Versus Control Group Patients
WHO status of subjects at timepoints from baseline to day 28
- 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
- Death
Measured: 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
National Early Warning Score assessed between baseline and Day 29 on subjects in 20, 40 mg TID NP-120 arms versus control group
The National Early Warning Score (NEWS) scale is a composite of 7 physiological parameters: Respiration Rate (per minute),Oxygen Saturations (%), Any Supplemental Oxygen, Temperature (°C), Systolic BP (mmHg), Heart Rate (per minute), Level of Consciousness. The aggregate results from all 7 physiological parameters are used to obtain the NEW Score., ranging from 0 - 20. Higher values reflect a worse outcome.
Measured: Days 3, 5, 8, 11, 25, 29
Rate of Mechanical Ventilation in IP Versus Control Group Patients
Rate of mechanical ventilation in 20 and 40 mg TID NP-120 versus control group
Measured: Up to Day 28
Duration of Mechanical Ventilation (if Applicable) in IP Versus Control Group Patients
Duration of mechanical ventilation in 20 and 40 mg TID subjects versus control who experience mechanical ventilation
Measured: Up to day 28
Duration of Supplemental Oxygen in IP Versus Control Group Patients
Duration in patients only receiving supplemental oxygen in IP versus control group up to Day 29
Measured: Up to Day 29
Time to Return to Room Pressure (SpO2 > 94%) on Room Air
Time to return to room pressure (SpO2 > 94%) on room air in patients in 20, 40 mg TID NP-120 groups versus control group with 94% blood oxygen levels at enrolment
Time-to-event endpoints with competing risk were analysed for each dosing group using the Cumulative Incidence Function-CIF (KM) graphical display. Data represents the time (in Days) it took for all participants in the group to return to room pressure air (e.g. the time when the CIF curve hit 100%).
Measured: Up to Day 29
Duration in ICU (if Applicable) in IP Versus Control Group Patients
Duration of subject in ICU in 20 and 40 TID mg groups versus control group patients
Measured: Up to Day 29
Rate of Mortality in IP Versus Control Group Patients
Rate of Overall Mortality in 20, 40 mg TID groups versus control group
Measured: Up to Day 29
Duration of Hospitalization in IP Versus Control Group Patients
Measured: Day 15, 28
Time to Discharge in IP Versus Control Group Patients
Measured: 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
Measured: Up to day 15, day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2020
- Study start5 Aug 2020
- Primary completion24 Dec 2020
- Study completion26 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for COVIDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 168 participants (actual)
Sponsor and investigators
- Lead sponsor
- Algernon Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Novotech (Australia)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04382924
- Sponsor's protocol ID
- AGN120-3
- Status last verified
- Dec 2021
- First submitted
- 8 May 2020
- Last updated
- 3 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Open Label Phase 2b/3 Study of the Safety and Efficacy of NP-120 (Ifenprodil) for the Treatment of Hospitalized Patient With Confirmed COVID-19 Disease
- ClinicalTrials.gov ID
- NCT04382924
- Acronym / sponsor ID
- AGN120-3
- Conditions
- COVID
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 168 participants (actual)
- Lead sponsor
- Algernon PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Novotech (Australia)
- Study start
- 5 Aug 2020 (actual)
- Primary completion
- 24 Dec 2020 (actual)
- Study completion
- 26 Jan 2021 (actual)
- First posted
- 11 May 2020 (actual)
- Results
- Posted 3 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 World Health Organization (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 150 subjects. Subject clinical status (on a 7-point ordinal scale) at day 15 in treatment versus the control group is the default primary endpoint.
Detailed description
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 Phase 2b/3 trial is to determine the safety and efficacy of NP-120 in the treatment of COVID-19 infection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm A | Experimental | Drug: NP-120 (Ifenprodil)NP-120 (Ifenprodil) 20 mg TID + Standard of Care |
| Control Arm | No intervention | –Standard of Care only |
| Treatment Arm B | Experimental | Drug: NP-120 (Ifenprodil)NP-120 (Ifenprodil) 40 mg TID + Standard of Care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male and female subjects aged ≥18 years of age
- Confirmed coronavirus infection
- Must be hospitalized and requiring supplemental oxygen, or on non-invasive ventilation or high flow oxygen devices (Score of 4 or 5 on WHO Ordinal Clinical Scale)
- Female subjects of childbearing potential who are sexually active with a non-sterilized male partner must use at least 1 highly effective method of contraception (e.g. oral contraceptives, intrauterine device, diaphragm plus spermicide) from the time of screening and must agree to continue using such precautions for 90 days after the final dose of study drug(s)
- Non-sterilized males who are sexually active with a female partner of childbearing potential must use condom plus spermicide from day 1 through 90 days after receipt of the last dose of study drug(s)
Key exclusion criteria (11 listed)
- Patients with vasodilatory shock, orthostatic hypotension, hypotension, or tachycardia at screening/baseline
- Patients experiencing cerebral hemorrhage or cerebral infarction at baseline
- ALT/AST > 5 times the upper limit of normal; Child-Pugh Score 10 to 15
- Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR < 30)
- Patients on mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NP-120 (Ifenprodil)Ifenprodil, 20 mg TID Ifenprodil, 40 mg TID | Drug | Treatment Arm A, Treatment Arm B |
Primary outcome
Patient Clinical Status (on the WHO 7-point Ordinal Scale) at Day 15 in IP Versus SOC Control Group Patients:
Time frame: Day 15
1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices 6. Hospitalized, on invasive mechanical ventilation or ECMO 7. Death
11 secondary outcomes
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: Up to Day 28
Duration of Mechanical Ventilation (if Applicable) in IP Versus Control Group Patients
Time frame: Up to day 28
Duration of Supplemental Oxygen in IP Versus Control Group Patients
Time frame: Up to Day 29
Time to Return to Room Pressure (SpO2 > 94%) on Room Air
Time frame: Up to Day 29
Duration in ICU (if Applicable) in IP Versus Control Group Patients
Time frame: Up to Day 29
Rate of Mortality in IP Versus Control Group Patients
Time frame: Up to Day 29
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
10 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing NP-120 (Ifenprodil) in people with COVID, run by Algernon Pharmaceuticals at 10 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Philippines, Australia, Romania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patient Clinical Status (on the WHO 7-point Ordinal Scale) at Day 15 in IP Versus SOC Control Group Patients: (time frame: Day 15). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2021.