Azeliragon for COVID-19

Not currently recruiting at 2 trial locations

Overseen By Pennelope Kunkle

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: The University of Texas Medical Branch, Galveston

Must not be taking: Strong CYP2C8 inhibitors

Disqualifiers: Intubation, Dialysis, Liver disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 14 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new drug, azeliragon, can help treat people hospitalized with COVID-19 or pneumonia. Researchers aim to determine if azeliragon improves symptoms such as cough, chest pain, and shortness of breath. The trial includes different groups, with some patients receiving azeliragon and others receiving a placebo (a pill with no active drug). It suits patients admitted to the hospital with a diagnosis of COVID-19 or pneumonia in the last 48 hours and experiencing symptoms like a strong cough or difficulty breathing. As a Phase 2, Phase 3 trial, this study measures how well azeliragon works in an initial group and represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for this trial?

The trial does not specify if you need to stop taking your current medications, but you cannot take strong inhibitors of CYP2C8. It's best to discuss your medications with the trial team.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take strong inhibitors of CYP2C8 while participating.

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

Research shows that azeliragon might help treat inflammation from lung infections like COVID-19. In studies, azeliragon has been tested on human lung tissue and found to reduce virus-induced inflammation, which is promising.

Although specific safety details from these trials aren't available, azeliragon's testing in both Phase 2 and Phase 3 trials suggests it has demonstrated some level of safety. Phase 2 trials primarily assess the treatment's safety and potential side effects. By Phase 3, a treatment has shown enough safety in earlier trials to be tested on more people.

If azeliragon had been unsafe in earlier trials, it wouldn't have advanced to this stage. However, anyone considering joining a trial should discuss potential risks and benefits with a healthcare provider. ^{1 2 3 4 5}

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

Researchers are excited about azeliragon for COVID-19 because it offers a fresh approach compared to traditional treatments like antivirals and corticosteroids. Unlike these standard treatments, azeliragon works by targeting the RAGE (receptor for advanced glycation end-products) pathway, which plays a role in inflammation and immune response. This unique mechanism could potentially reduce inflammation and lung damage, which are major issues in severe COVID-19 cases. If successful, azeliragon might offer a new way to manage COVID-19 symptoms more effectively.

What evidence suggests that azeliragon might be an effective treatment for COVID-19?

This trial investigates whether azeliragon could help treat COVID-19 and pneumonia. Participants will join different arms, receiving either azeliragon or a placebo. Currently, solid evidence does not exist to confirm azeliragon's effectiveness for these illnesses, and the studies mainly aim to understand its potential benefits. Originally developed for other purposes, researchers are exploring if azeliragon could reduce inflammation or assist the immune system in COVID-19 patients. More research is necessary to determine azeliragon's effectiveness for COVID-19. ^{3 6 7 8 9}

Who Is on the Research Team?

Lucas S. Blanton, MD

Principal Investigator

University of Texas

Are You a Good Fit for This Trial?

This trial is for hospitalized patients with COVID-19 or pneumonia showing symptoms like cough, chest pain, or low oxygen levels. They must have been admitted within the last 48 hours and be able to consent. It's not for those with severe liver issues, likely need for intubation soon after admission, certain heart conditions, pregnant or breastfeeding women without effective contraception, or allergies to azeliragon.

Inclusion Criteria

I was diagnosed with pneumonia or COVID-19 within the first 2 days of my hospital stay.

I have at least two symptoms: cough, chest pain, shortness of breath, or low oxygen levels.

Provide informed consent to participate in the study (by participant or legally-acceptable representative)

Exclusion Criteria

Your heart's electrical activity, as measured by an ECG, shows a prolonged QT interval.

I am not pregnant, breastfeeding, and I use effective birth control.

I was on dialysis when I was admitted.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive azeliragon or placebo while hospitalized for COVID-19 or pneumonia

14 days

Daily monitoring during hospitalization

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Azeliragon
• Placebo

Trial Overview Researchers are testing a new drug called Azeliragon against a placebo in people hospitalized with COVID-19 or pneumonia. The study is randomized and double-blind, meaning neither the doctors nor the patients know who gets the real drug versus a dummy pill.

How Is the Trial Designed?

Group I: Phase 3 azeliragon Experimental Treatment 1 Intervention

Group II: Phase 2 azeliragon Experimental Treatment 1 Intervention

Group III: Phase 2 placebo Placebo Group 1 Intervention

Group IV: Phase 3 placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

The University of Texas Medical Branch, Galveston

Lead Sponsor

Trials

263

Recruited

55,400+

Salim S. Hayek

Lead Sponsor

Trials

1

Recruited

140+

Published Research Related to This Trial

In a study involving 550 adults with severe, uncontrolled asthma, tezepelumab significantly reduced annualized asthma exacerbation rates by 55-83% compared to placebo, demonstrating its efficacy in managing severe asthma.

Tezepelumab also lowered levels of various type 2 inflammatory biomarkers, indicating a reduction in airway inflammation, regardless of the patients' baseline biomarker profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline type 2 biomarker levels and response to tezepelumab in severe asthma. Corren, J., Pham, TH., Garcia Gil, E., et al.[2022]

In a phase 2a trial involving 81 adult asthma patients, the inhaled TLR9 agonist AZD1419 was found to be safe and well tolerated, with no serious adverse events linked to the treatment.

Although AZD1419 reduced markers of type 2 inflammation and induced a T-helper cell type 1 response, it did not significantly improve asthma control compared to placebo, indicating that further research is needed to understand its efficacy in managing asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 2a, Double-Blind, Placebo-controlled Randomized Trial of Inhaled TLR9 Agonist AZD1419 in Asthma. Psallidas, I., Backer, V., Kuna, P., et al.[2021]

Azelastine eye drops significantly reduced symptoms of seasonal allergic conjunctivitis in 85.4% of patients after 3 days of treatment, showing superior efficacy compared to placebo and sodium cromoglycate.

The study involved 144 participants aged 16 to 65 over a 2-week period, and while both azelastine and sodium cromoglycate were effective, azelastine was associated with a higher satisfaction rate (90.0% vs. 81.3%) and had manageable side effects, primarily transient application site reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy and tolerability of topically administered azelastine, sodium cromoglycate and placebo in the treatment of seasonal allergic conjunctivitis and rhino-conjunctivitis. James, IG., Campbell, LM., Harrison, JM., et al.[2019]

In a phase 2 trial involving non-hospitalized adults with symptomatic SARS-CoV-2, oral TQ Formula (TQF) was well-tolerated and showed a faster decline in total symptom burden compared to placebo, indicating potential efficacy.

Although the median time-to-sustained-clinical-response (SCR) did not reach statistical significance, TQF demonstrated promising effects on immune response, increasing cytotoxic CD8+ and helper CD4+ T lymphocytes, and showed in vitro activity against multiple SARS-CoV-2 variants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of ThymoQuinone Formula (TQF) for Treating Outpatient SARS-CoV-2. Bencheqroun, H., Ahmed, Y., Kocak, M., et al.[2023]

In a study involving 32 hospitalized COVID-19 patients, the immune modulator azoximer bromide (AZB) was found to be safe and well tolerated, with no major toxicities reported during treatment alongside standard care.

Patients treated with AZB showed significant clinical improvement, including decreased severity of symptoms and normalization of oxygen saturation levels, with most recovering from pneumonia by days 10-12.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of azoximer bromide (Polyoxidonium®) in patients hospitalized with coronavirus disease (COVID-19): an open-label, multicentre, interventional clinical study. Efimov, SV., Matsiyeuskaya, NV., Boytsova, OV., et al.[2021]

In a study of 81 hospitalized COVID-19 patients, the immunomodulator azoximer bromide (AZB) was found to be safe and well tolerated when used alongside standard care, with no deaths reported during the study period.

Patients receiving AZB showed notable clinical improvement in their condition, as indicated by a significant reduction in their ordinal scale scores, suggesting potential benefits in recovery compared to historical controls, despite the need for further randomized studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label use of an aliphatic polyamine immunomodulator in patients hospitalized with COVID-19. Efimov, SV., Matsiyeuskaya, NV., Boytsova, OV., et al.[2022]

In a phase 2 trial involving 436 patients with uncontrolled moderate-to-severe asthma, tezepelumab significantly reduced the annualized rate of asthma exacerbations by 61% to 71% compared to placebo, demonstrating its efficacy in managing asthma symptoms.

Tezepelumab also improved lung function, as indicated by higher forced expiratory volume in 1 second (FEV1) across all dosing groups, with minimal adverse events leading to discontinuation, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezepelumab in Adults with Uncontrolled Asthma. Corren, J., Parnes, JR., Wang, L., et al.[2022]

In a phase 3 trial with 21,634 participants, the AZD1222 vaccine demonstrated a vaccine efficacy of 67.0% against symptomatic COVID-19, indicating it is effective in reducing the risk of infection.

The vaccine showed durable protection over 6 months, with a high efficacy of 92.1% against severe or critical disease, and no new safety concerns were reported, confirming its safety and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durability of protection and immunogenicity of AZD1222 (ChAdOx1 nCoV-19) COVID-19 vaccine over 6 months. Sobieszczyk, ME., Maaske, J., Falsey, AR., et al.[2023]

A case of aseptic meningitis was reported in a 26-year-old healthcare worker after receiving the first dose of the AZD1222 COVID-19 vaccine, highlighting a potential neurological side effect.

While the AZD1222 vaccine is widely used and effective against COVID-19, this case suggests that healthcare providers should be aware of rare neurological complications following vaccination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aseptic meningitis following AZD1222 COVID-19 vaccination. Zavari, A., Hamidabad, NM., Hassanzadeh, M.[2022]

Azelastine nasal spray did not negatively affect ciliary beat activity in guinea pigs during acute experiments, suggesting it is safe for nasal function.

After 26 weeks of daily application in rats and dogs, azelastine did not cause any inflammatory or atrophic changes in the nasal mucosa, indicating its long-term safety for local use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental studies on acute and chronic action of azelastine on nasal mucosa in guinea pigs, rats and dogs. Achterrath-Tuckermann, U., Berthold, K., Roux, J., et al.[2012]

In a randomized trial with 90 SARS-CoV-2 positive patients, azelastine nasal spray significantly reduced viral loads, especially at a concentration of 0.1%, compared to placebo, indicating its potential as an antiviral treatment.

Patients treated with azelastine also experienced earlier and more frequent negative PCR results, with no safety concerns reported across all treatment groups, suggesting that azelastine is safe and effective for early COVID-19 infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early intervention with azelastine nasal spray may reduce viral load in SARS-CoV-2 infected patients. Klussmann, JP., Grosheva, M., Meiser, P., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05815485

A Randomized, Double-Blind, Placebo-Controlled Phase 2 ... In this study, they are learning the effects of azeliragon patients hospitalized for COVID-19 or pneumonia.

2. withpower.com withpower.com/trial/phase-2-and-3-covid-19-3-2023-2fdef

Azeliragon for COVID-19 · Info for Participants The available research does not provide any data supporting the effectiveness of Azeliragon for COVID-19. Instead, it discusses other treatments like azoximer ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05815485/a-randomized-double-blind-placebo-controlled-phase-2-3-study-to-determine-the-safety-and-effectiveness-of-azeliragon-in-the-treatment-of-patients-hospitalized-for-coronavirus-disease-2019-covid-19-or-pneumonia

A Randomized, Double-Blind, Placebo-Controlled Phase 2 ... In this study, they are learning the effects of azeliragon patients hospitalized for COVID-19 or pneumonia.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12494476/

Real-World Evaluation Study of Azvudine for the Treatment ... Background: Azvudine, as an antiviral drug, has been approved for the treatment of COVID-19, and multiple randomized controlled trials (RCTs) ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02080364?term=AREA%5BBasicSearch%5D(AZELIRAGON)&rank=8&tab=results

Evaluation of the Efficacy and Safety of Azeliragon ... Submission of false or misleading clinical trial information; Failure to submit primary and secondary outcomes. Correction: Shown when the FDA confirms that the ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05815485

Study Details | NCT05815485 | A Randomized, Double- ... In this study, they are learning the effects of azeliragon patients hospitalized for COVID-19 or pneumonia. Official Title. A Randomized, Double-Blind, Placebo- ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12450139/

Five-Year Safety and Efficacy Outcomes with Ofatumumab ... Here, we further characterise the safety and efficacy of ofatumumab up to 5 years by discussing infection outcomes in the COVID-19 era and ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04436276

NCT04436276 | A Study of Ad26.COV2.S in Adults (COVID ... The purpose of the study is to assess the safety, reactogenicity, and immunogenicity of Ad26.COV2.S at 2 dose levels, administered intramuscularly (IM) as a ...

9. wyss.harvard.edu wyss.harvard.edu/news/cantex-licenses-intellectual-property-from-harvard-university-to-develop-repurposed-drug-identified-by-wyss-institute-to-treat-inflammatory-lung-diseases-including-covid-19/

Cantex licenses intellectual property from Harvard ... Organ Chip studies revealed azeliragon can reduce virus-associated inflammation in human lung tissue.