AV-001 for COVID-19

Not currently recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vasomune Therapeutics, Inc.

Disqualifiers: Pregnancy, Septic shock, Organ failure, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AV-001 Injection (a Vasculotide analog) to determine its safety and effectiveness for hospitalized pneumonia patients requiring extra oxygen. The study aims to discover if this treatment can reduce symptoms and improve recovery times compared to a placebo. Participants will receive either the actual treatment or a placebo, alongside their usual care. Suitable candidates have been hospitalized with pneumonia, need oxygen, and exhibit symptoms like high fever or difficulty breathing. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop your current medications. However, if you have a serious medical condition or are taking certain medications that could interfere with the study, you may not be eligible to participate.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have a serious medical condition or are taking certain medications that could interfere with the study, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows no specific safety information for AV-001 when used for COVID-19. However, the trial's second phase indicates that earlier studies have demonstrated its basic safety for humans. This suggests the treatment is safe enough for further testing. The Data Safety Monitoring Board oversees the study, monitoring the treatment's safety and adjusting doses based on new trial data. This oversight ensures careful management of any potential risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for COVID-19?

Unlike the standard treatments for COVID-19, which often include antiviral drugs like Remdesivir and supportive care, AV-001 offers a unique approach by potentially modulating immune responses. Researchers are excited about AV-001 because it is designed to target specific pathways in the body, possibly reducing inflammation and improving patient outcomes more effectively. Additionally, its dosing flexibility, with the ability to tailor doses based on patient response, offers a customized treatment option that could enhance safety and efficacy.

What evidence suggests that AV-001 Injection might be an effective treatment for COVID-19?

Research has shown that AV-001 might help treat COVID-19 by protecting lung cells. This treatment reduces blood vessel leakage, potentially minimizing lung damage from the virus. Previous patients demonstrated that AV-001 is safe and well-tolerated, with no serious side effects reported. Early studies suggested it effectively reduces symptoms in patients with severe COVID-19. In this trial, participants will receive either AV-001 Injection or a placebo, both alongside standard care. AV-001 is designed to assist those with pneumonia who need extra oxygen, a common requirement in severe cases. These findings support AV-001 as a promising treatment option. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for hospitalized patients with presumed pneumonia needing extra oxygen but not on mechanical ventilation or ECMO. They should have symptoms like new cough, fever, or breathlessness and signs of lung infection on imaging. Adults over 70 must be mentally stable and women able to bear children need effective contraception.

Inclusion Criteria

I have new or worsening symptoms like coughing, difficulty breathing, or changes in my sputum.

I am using effective birth control.

I have a high fever, fast breathing, unusual white blood cell count, or confusion if over 70.

Exclusion Criteria

I am on a ventilator or ECMO machine.

Pregnant and/or lactating women

Patients included in any other interventional trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive AV-001 Injection or placebo daily until the earlier of day 28 or hospital discharge

Up to 4 weeks

Daily visits for administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AV-001 Injection
• AV-001 Placebo Injection

Trial Overview The study tests AV-001 Injection versus a placebo in addition to standard care for pneumonia. It's randomized and double-blind, meaning neither the doctors nor patients know who gets the real treatment. Patients receive daily doses until day 28 or hospital discharge.

How Is the Trial Designed?

Group I: AV-001 Injection with standard of care (SOC). Active Control 1 Intervention

A total of 120 eligible patients (20 patients in each of cohort 1, 2 and 3 and 60 patients in cohort 4) will be randomized in a 1:1 ratio to receive either AV-001 Injection or AV-001 placebo Injection, together with standard of care (SOC). Doses of AV-001 Injection will start with 12.5 μg/kg/day in cohort 1 and are anticipated to increase to 25 μg/kg/day in cohort 2, 56 μg/kg/day in cohort 3 and to be determined (TBD) in cohort 4. The dose for cohort 4 will be determined by the Data Safety Monitoring Board (DSMB) based on emerging data from cohorts 1, 2 and 3.

Group II: AV-001 Placebo Injection with standard of care (SOC). Placebo Group 1 Intervention

A total of 120 eligible patients (20 patients in each of cohort 1, 2 and 3 and 60 patients in cohort 4) will be randomized in a 1:1 ratio to receive either AV-001 Injection or AV-001 placebo Injection, together with standard of care (SOC).

AV-001 Injection is already approved in United States, Canada for the following indications:

Approved in United States as AV-001 for:

• None approved; under investigation for Acute Respiratory Distress Syndrome (ARDS), pneumonia, and other conditions

Approved in Canada as AV-001 for:

• None approved; under investigation for Acute Respiratory Distress Syndrome (ARDS), pneumonia, and other conditions

Who Is Running the Clinical Trial?

Vasomune Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

170+

Published Research Related to This Trial

Aerosol administration of soluble human recombinant ACE2 (APN01) has shown the ability to neutralize SARS-CoV-2 in laboratory tests and has been well-tolerated in preliminary animal studies, indicating potential for use in humans.

Toxicology testing in dogs demonstrated no significant adverse effects from twice-daily aerosol administration over two weeks, paving the way for a Phase I clinical trial in healthy volunteers to further assess safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of an aerosol intervention for COVID-19 disease: Tolerability of soluble ACE2 (APN01) administered via nebulizer. Shoemaker, RH., Panettieri, RA., Libutti, SK., et al.[2022]

The CVnCoV vaccine candidate demonstrated low efficacy in a phase 3 trial, which was linked to the specific dose used and the presence of SARS-CoV-2 variants.

The vaccine's low efficacy was predicted by the neutralizing antibody response it generated, suggesting that both dosage and immune response play critical roles in its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relating In Vitro Neutralization Level and Protection in the CVnCoV (CUREVAC) Trial. Cromer, D., Reynaldi, A., Steain, M., et al.[2023]

A new inhaled formulation of angiotensin receptor blockers (ARBs) has been developed to treat COVID-19, addressing safety concerns associated with oral administration and aiming for effective lung delivery.

In vitro studies show that this nanosuspension formulation is stable, retains drug activity, and effectively inhibits SARS-CoV-2 replication, with promising lung pharmacokinetics and tolerability observed in animal models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Telmisartan Nanosuspension for Inhaled Therapy of COVID-19 Lung Disease and Other Respiratory Infections. Chen, D., Yun, X., Lee, D., et al.[2023]

In a study of 377 patients treated with intravitreal aflibercept (IVT-AFL) for macular edema due to central retinal vein occlusion (CRVO), the treatment showed a favorable safety profile with only 5.84% experiencing adverse events over 24 months.

The treatment led to significant improvements in best corrected visual acuity (BCVA) and central retinal thickness (CRT), although the degree of improvement was less than that seen in randomized controlled trials, suggesting potential undertreatment in the clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data on Intravitreal Aflibercept for Macular Edema Secondary to Central Retinal Vein Occlusion: 24-Month Outcomes. Shimura, M., Fukumatsu, M., Tsujimura, J., et al.[2022]

The study found that withdrawing and storing the therapeutic antibody faricimab in specialized syringes for up to 37 days did not affect its structural integrity or bi-specific binding properties, ensuring its efficacy as a treatment.

Analyses showed no signs of degradation or aggregation of faricimab, indicating that it remains stable and effective for use in intravitreal injections during the storage period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical compounding and storage of faricimab in a syringe for intravitreal injection do not impair stability and bi-specific binding properties. Jørstad, ØK., Foss, S., Gjølberg, TT., et al.[2023]

In a study of 126 patients at risk for allergies to SARS-CoV-2 vaccines, 5% were found to have severe allergies to polyethylene glycol (PEG), which contraindicates the use of PEG-containing vaccines.

The skin testing protocol using PEG 1500 was effective in identifying PEG allergies, allowing 100 patients to safely receive vaccines containing PEG 2000 after confirming they did not have the allergy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polythylene glycol severe allergy and SARS-CoV-2 vaccines: usefulness of testing with PEG 1500 extract. Gaspar, A., Moura, AL., Cruz, C., et al.[2023]

In a systematic review of 12 studies involving 45,380 participants, it was found that 35.2% of placebo recipients reported systemic adverse events (AEs) after the first dose of a COVID-19 vaccine, indicating a significant nocebo effect.

While vaccine recipients reported more AEs than those receiving placebo, a substantial portion of reported AEs in the placebo group (76.0% after the first dose and 51.8% after the second dose) were attributed to nocebo responses, highlighting the importance of addressing these concerns in vaccination programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials: A Systematic Review and Meta-analysis. Haas, JW., Bender, FL., Ballou, S., et al.[2022]

In a study of 46 individuals with suspected allergic reactions to the first COVID-19 vaccine dose, only 1 patient tested positive for an allergy to PEG2000, indicating a low incidence of allergic reactions to vaccine additives.

All patients, including the one with a positive test, tolerated the second dose of mRNA or vector-based vaccines well, suggesting that COVID-19 vaccines can be safely administered even to those with suspected allergies from the first dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-dose COVID-19 vaccines are well tolerated in patients with allergic reactions to the first dose - a single center experience. Puxkandl, V., Bangerl, T., Hanfstingl, K., et al.[2022]

In a phase III trial (COVACTA) involving hospitalized patients with severe COVID-19 pneumonia, tocilizumab did not significantly reduce 28-day mortality compared to a placebo, indicating limited efficacy for this treatment in this patient population.

A real-world external comparator arm, matched to COVACTA participants, confirmed these findings, showing no significant difference in mortality rates between those treated with tocilizumab and those not exposed to the drug, suggesting that external comparators can effectively supplement RCT data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Evidence to Supplement Randomized Clinical Trials: Tocilizumab for Severe COVID-19 Pneumonia vs. a Cohort Receiving Standard of Care. Skarbinski, J., Fischer, H., Hong, V., et al.[2023]

Researchers developed a new injectable formulation of Niclosamide nanoparticles (BSA-NIC-PEG NPs) that could effectively target the SARS-CoV-2 virus, showing promising stability and dispersibility in vitro.

While initial in vitro results are encouraging, further in vivo studies in virus-infected models are necessary to confirm the efficacy of this formulation, especially for elderly patients with hypoalbuminemia often seen in COVID-19 cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Injectable niclosamide nanohybrid as an anti-SARS-CoV-2 strategy. Rejinold, NS., Piao, H., Jin, GW., et al.[2022]

In a 48-week study involving 100 patients with macular edema due to retinal vein occlusion, treatment with ranibizumab led to a significant improvement in best-corrected visual acuity (BCVA) by an average of 7.7 letters, indicating its efficacy in a real-world setting.

The treatment also resulted in a significant reduction in central retinal thickness, from an average of 479.9 μm to 284.9 μm, demonstrating its effectiveness in reducing edema without any reported serious safety issues like endophthalmitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sub-optimal gain in vision in retinal vein occlusion due to under-treatment in the real world: results from an open-label prospective study of Intravitreal Ranibizumab. Narayanan, R., Kelkar, A., Abbas, Z., et al.[2021]

Intranasal administration of soluble human recombinant ACE2 (APN01) in a mouse model significantly reduced weight loss and prevented death from SARS-CoV-2 infection, suggesting its potential efficacy in mitigating COVID-19 effects.

Aerosolized APN01 maintained its ability to bind the virus and perform its enzymatic function, with no notable toxicities observed in dogs during toxicity testing, paving the way for a Phase I clinical trial in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a novel, pan-variant aerosol intervention for COVID-19. Shoemaker, RH., Panettieri, RA., Libutti, SK., et al.[2022]

In the BRAVO and CRUISE trials involving patients with macular edema from retinal vein occlusion, both doses of ranibizumab (0.3 mg and 0.5 mg) led to significant anatomical and visual improvements just 7 days after treatment.

After an initial 6-month treatment period, PRN (as needed) ranibizumab injections maintained visual improvements, although control group patients receiving PRN treatment showed less visual improvement compared to those in the treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[BRAVO and CRUISE: ranibizumab for the treatment of macular edema secondary to retinal vein occlusion]. Figueroa, MS., Ruiz Moreno, JM.[2019]

In a study of 57 patients with macular edema due to branch retinal vein occlusion, all three treatments (aflibercept, ranibizumab, and dexamethasone implant) showed similar improvements in visual acuity and reduction in central macular thickness over six months.

While dexamethasone implant resulted in higher visual acuity at all time points, it also had more side effects, including increased intraocular pressure and cataract progression, compared to the anti-VEGF treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Real-Life Study: Intravitreal Aflibercept, Ranibizumab and Dexamethasone for Macular Edema Secondary to Branch Retinal Vein Occlusion. Bayat, AH., Bölükbasi, S., Erden, B., et al.[2022]

Capillary leak syndrome (CLS) was reported as a rare adverse event following COVID-19 vaccination, with 84 cases identified out of over 1.3 million reports, primarily associated with viral vector vaccines like ChAdOx1-SARS-COV-2 and Ad26.COV2-S.

The analysis indicated a significantly lower probability of CLS occurrence after mRNA vaccines (like BNT162b2 and mRNA-1273) compared to viral vector vaccines, suggesting a potential safety concern particularly with the Ad26.COV2-S vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capillary leak syndrome following COVID-19 vaccination: Data from the European pharmacovigilance database Eudravigilance. Ruggiero, R., Balzano, N., Di Napoli, R., et al.[2022]

Citations

1. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/av-001-vasomune-therapeutics-coronavirus-disease-2019-covid-19-associated-acute-respiratory-distress-syndrome-likelihood-of-approval/

AV-001 by Vasomune Therapeutics for Coronavirus ... AV-001 is under development for the treatment of pathogen-induced acute respiratory distress syndrome (ARDS), acute kidney injury, acute lung ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05123755

NCT05123755 | Phase 2a Multiple Ascending Dose Study ... Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/ ...

3. anges.co.jp anges.co.jp/pdf_news/public/KiwVtZE3tO9NiylJy6huNH7oZcw1HOzC.pdf

COVID-19 Treatment AV-001: Preliminary Positive Phase 1 ... In this study, AV-001 was safe and well tolerated and there were no discontinuations due to study medication, serious adverse events (SAEs), ...

4. delta.larvol.com delta.larvol.com/Products/?ProductId=ce6fe517-1d55-4250-852b-915650fba1a9

AV-001 / Vasomune Therap, AnGes MG Synthetic Tie2 Agonist AV-001 Protects Against Endothelial Cell Permeability Induced by SARS-CoV-2 Infection/COVID-19 (ATS 2025) - "AV-001 can increase ...

5. businesswire.com businesswire.com/news/home/20220118005293/en/Vasomune-and-AnGes-Announce-First-Patient-Enrolled-in-Phase-2a-Clinical-Study-Evaluating-AV-001-for-the-Treatment-of-Severe-COVID-19-Disease

Vasomune and AnGes Announce First Patient Enrolled in ... Vasomune and AnGes Announce First Patient Enrolled in Phase 2a Clinical Study Evaluating AV-001 for the Treatment of Severe COVID-19 Disease.

6. withpower.com withpower.com/trial/phase-3-covid-19-10-2021-03cc4

AV-001 for COVID-19 · Info for Participants What safety data is available for AV-001 treatment for COVID-19? The provided research does not contain specific safety data for AV-001 treatment for COVID-19.

7. trial.medpath.com trial.medpath.com/news/b8a6ebde01c5cd3e/vasomune-to-present-late-breaking-data-on-av-001-s-protective-effects-against-covid-19-at-ats-conference

Vasomune to Present Late-Breaking Data on AV-001's ... Vasomune Therapeutics will present late-breaking research showing how their lead candidate AV-001 protects against endothelial cell permeability induced by SARS ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9803910/

Safety and efficacy of the two doses conjugated protein ... Safety and efficacy of the two doses conjugated protein-based SOBERANA-02 COVID-19 vaccine and of a heterologous three-dose combination with SOBERANA-Plus