Obeldesivir for RSV Infection

Recruiting in Palo Alto (17 mi)

+119 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Gilead Sciences

Must not be taking: Antimicrobials, Antivirals, Monoclonal antibodies

Disqualifiers: Hospitalization, Influenza, SARS-CoV-2, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The goal of this clinical study is to learn more about the study drug, obeldesivir (ODV; GS-5245), and how safe and effective it is in treating nonhospitalized adults with acute respiratory syncytial virus (RSV) infection. The researchers want to see if obeldesivir can help participants' symptoms get better faster. The primary objectives of this study are to evaluate the efficacy of ODV in reducing the duration of symptoms and to evaluate the safety and tolerability of ODV in nonhospitalized adult participants with acute RSV infection.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received any direct-acting antiviral drug or monoclonal antibody against RSV within 28 days or 5 half-lives before joining the trial.

What data supports the idea that Obeldesivir for RSV Infection is an effective treatment?

The available research does not provide any data on Obeldesivir for RSV Infection. Instead, it focuses on treatments for obesity, such as Rimonabant, Lorcaserin, and Phentermine/Topiramate, which are unrelated to RSV Infection. Therefore, there is no information here to support the effectiveness of Obeldesivir for RSV Infection. ^{1 2 3 4 5}

What safety data is available for Obeldesivir (GS-5245, ATV006) for RSV infection?

The provided research does not contain any safety data for Obeldesivir (GS-5245, ATV006) for RSV infection. The studies focus on adverse events related to anti-obesity medications, not on Obeldesivir or its related names. ^{6 7 8 9 10}

Is the drug Obeldesivir a promising treatment for RSV infection?

The information provided does not directly discuss Obeldesivir's effectiveness against RSV infection. It focuses on its potential against coronaviruses like SARS-CoV-2. Therefore, we cannot conclude that Obeldesivir is a promising treatment for RSV based on the given data. ^{11 12 13 14 15}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

Adults over 60, or those with moderate/severe COPD, asthma, bronchiectasis, interstitial lung disease (like pulmonary fibrosis), pulmonary hypertension, or chronic heart disease can join. They must have confirmed RSV infection within the past 3 days and show new or worsening symptoms of at least moderate severity.

Inclusion Criteria

I am over 60 and have not received an RSV vaccine.

RSV infection confirmed ≤ 3 days before randomization

I have recently developed or worsened symptoms of an RSV infection.

Exclusion Criteria

Pregnant at screening

I have a history of cystic fibrosis.

I have been on dialysis or had moderate to severe kidney problems in the last 6 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive obeldesivir or placebo for 5 days

1 week

Daily visits (in-person or virtual) for 5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Weekly visits (in-person or virtual)

Long-term follow-up

Participants are monitored for RSV-related outcomes and safety through Day 29

4 weeks

Treatment Details

Interventions

• Obeldesivir (Anti-viral)

Trial Overview The trial is testing Obeldesivir's effectiveness in reducing symptom duration for nonhospitalized adults with acute RSV. Participants will either receive Obeldesivir or a placebo to compare outcomes.

Participant Groups

Group I: Placebo comparator: Obeldesivir Placebo Experimental Treatment 1 Intervention

Participants will receive obeldesivir placebo for 5 days

Group II: Obeldesivir (ODV) Experimental Treatment 1 Intervention

Participants will receive obeldesivir for 5 days

Who Is Running the Clinical Trial?

Gilead Sciences

Lead Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Findings from Research

In a Phase 4 trial involving 222 patients with obesity and type 2 diabetes, rimonabant (20 mg/day) combined with lifestyle counseling led to significant improvements in body weight, body mass index, and HDL cholesterol after one year, compared to placebo.

Despite these benefits, rimonabant was associated with a deterioration in quality of life and showed no significant improvement in overall cardiovascular risk factors, leading to its suspension from the market due to psychiatric side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rimonabant improves obesity but not the overall cardiovascular risk and quality of life; results from CARDIO-REDUSE (CArdiometabolic Risk reDuctIOn by Rimonabant: the Effectiveness in Daily practice and its USE). Boesten, JE., Kaper, J., Stoffers, HE., et al.[2019]

Losing just 5% of body weight can lead to significant health improvements, but many individuals struggle to maintain weight loss through diet and exercise alone, highlighting the need for additional treatment options.

As of 2012, two new medications, lorcaserin and phentermine/topiramate, have been approved for long-term obesity treatment, and bariatric surgery is recommended for patients with severe obesity (BMI ≥40 or ≥35 with comorbidities) as a more intensive intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity consults--comprehensive obesity management in 2013: understanding the shifting paradigm. Kushner, RF., Apovian, CM., Fujioka, K.[2018]

Rimonabant, at a dosage of 20 mg per day, resulted in a significant weight loss of 4.7 kg compared to placebo after one year, indicating its efficacy as an anti-obesity agent in a meta-analysis of four trials involving 4105 participants.

However, rimonabant was associated with a higher incidence of adverse psychiatric events, including depressive mood disorders and anxiety, leading to a recommendation for increased monitoring by physicians due to the potential severity of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Christensen, R., Kristensen, PK., Bartels, EM., et al.[2022]

Oral lorcaserin is effective for weight management in obese and overweight adults, showing significant weight loss compared to placebo in three large studies over 12 months, with many participants achieving a ≥5% or ≥10% reduction in body weight.

Lorcaserin is generally well tolerated, with low rates of serious side effects like valvulopathy, and those who maintained weight loss after 12 months continued to do so better than those who switched to placebo, indicating its potential for long-term weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lorcaserin: a review of its use in chronic weight management. Hoy, SM.[2021]

Qsymia™, a once-daily oral capsule combining phentermine and extended-release topiramate, has been approved in the US for treating obesity, leveraging phentermine's appetite-suppressing effects and topiramate's ability to increase feelings of fullness.

The formulation is also being explored for potential benefits in treating sleep apnea and type 2 diabetes, indicating its broader therapeutic applications beyond weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phentermine and topiramate extended release (Qsymia™): first global approval. Cameron, F., Whiteside, G., McKeage, K.[2021]

In a review of 170 adverse drug reaction reports related to the antiobesity drug sibutramine, 34% indicated label-inconsistent use, highlighting potential safety risks associated with its prescription.

The analysis revealed that common violations included not adhering to the recommended starting dose and prescribing the drug to patients with a history of drug abuse, and a Dear Doctor Letter aimed at promoting proper use was found to be ineffective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Label-inconsistent use of sibutramine in spontaneous adverse drug reaction reports in Germany. Seebeck, J., Wulf, F., Sachs, B.[2019]

A total of 25 anti-obesity medications were withdrawn between 1964 and 2009, primarily due to adverse reactions related to their effects on monoamine neurotransmitters, with 80% of withdrawals supported by case reports.

The most common reasons for withdrawal included psychiatric disturbances, cardiotoxicity, and drug dependence, raising concerns about the safety of using medications that target neurotransmitters for obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing withdrawal of anti-obesity medicinal products because of adverse drug reactions: a systematic review. Onakpoya, IJ., Heneghan, CJ., Aronson, JK.[2022]

A comprehensive analysis of the FDA Adverse Event Reporting System revealed 18,675 unique adverse event reports linked to anti-obesity medications (AOMs) among 15,143 patients, highlighting significant safety concerns.

Serious adverse events included a fatality ratio of 4.9%, with cardiovascular complications being particularly prevalent, accounting for 31% of AEs related to phentermine, and indicating a need for ongoing safety monitoring of AOMs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Descriptive analysis of reported adverse events associated with anti-obesity medications using FDA Adverse Event Reporting System (FAERS) databases 2013-2020. Alsuhibani, A., Alrasheed, M., Gari, M., et al.[2022]

Presatovir (GS-5806) is a promising oral antiviral that effectively inhibits the fusion of respiratory syncytial virus (RSV) with host cells, showing favorable safety and pharmacokinetic profiles in two phase 1 studies involving healthy adults.

The studies demonstrated that presatovir can be administered once daily without regard to meals, and its exposure increases in a dose-proportional manner, supporting its potential for further clinical trials in treating RSV infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 First-in-Human, Single- and Multiple-Ascending Dose, and Food Effect Studies to Assess the Safety, Tolerability, and Pharmacokinetics of Presatovir for the Treatment of Respiratory Syncytial Virus Infection. German, P., Xin, Y., Chien, JW., et al.[2021]

GS-5806 is a highly effective oral RSV fusion inhibitor, showing a mean EC50 of 0.43 nM against various RSV clinical isolates and demonstrating dose-dependent antiviral efficacy in a cotton rat model.

In healthy human volunteers infected with RSV, GS-5806 resulted in a significant 4.2 log10 reduction in peak viral load and decreased disease severity compared to placebo, indicating its potential as a treatment for RSV infections in both infants and adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of an oral respiratory syncytial virus (RSV) fusion inhibitor (GS-5806) and clinical proof of concept in a human RSV challenge study. Mackman, RL., Sangi, M., Sperandio, D., et al.[2021]

In a Phase 2b trial involving 61 lung transplant recipients with RSV infection, the RSV fusion inhibitor presatovir did not significantly reduce nasal RSV load or improve respiratory symptoms compared to placebo.

Despite the lack of efficacy in reducing RSV levels or improving lung function, presatovir was generally well tolerated by patients, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of presatovir for respiratory syncytial virus after lung transplant. Gottlieb, J., Torres, F., Haddad, T., et al.[2023]

GS-5245, an oral prodrug targeting the RNA-dependent viral RNA polymerase, shows broad antiviral activity against multiple coronaviruses, including SARS-CoV-2 variants like BA.1, in vitro and in mouse models.

In combination with the protease inhibitor nirmatrelvir, GS-5245 demonstrated increased efficacy against SARS-CoV-2, suggesting it could be a valuable addition to treatment strategies for COVID-19, particularly for patients needing more effective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of the oral nucleoside prodrug GS-5245 (Obeldesivir) against SARS-CoV-2 and coronaviruses with pandemic potential. Martinez, DR., Moreira, FR., Zweigart, MR., et al.[2023]

In a study involving healthy adults infected with RSV, presatovir effectively reduced viral load and disease severity in a dose-dependent manner, demonstrating its potential as a treatment for RSV infections.

Although some RSV strains developed resistance to presatovir during treatment, this resistance did not significantly impact the overall clinical outcomes, suggesting that presatovir remains an effective option for managing RSV despite the emergence of resistant strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Resistance Assessment Following Administration of Respiratory Syncytial Virus (RSV) Fusion Inhibitor Presatovir to Participants Experimentally Infected With RSV. Stray, K., Perron, M., Porter, DP., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Rimonabant improves obesity but not the overall cardiovascular risk and quality of life; results from CARDIO-REDUSE (CArdiometabolic Risk reDuctIOn by Rimonabant: the Effectiveness in Daily practice and its USE). [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Obesity consults--comprehensive obesity management in 2013: understanding the shifting paradigm. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Lorcaserin: a review of its use in chronic weight management. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Phentermine and topiramate extended release (Qsymia™): first global approval. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Label-inconsistent use of sibutramine in spontaneous adverse drug reaction reports in Germany. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Serious adverse events reported for antiobesity medicines: postmarketing experiences from the EU adverse event reporting system EudraVigilance. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Post-marketing withdrawal of anti-obesity medicinal products because of adverse drug reactions: a systematic review. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Antiobesity and antihyperglycemic effects of ginsenoside Rb1 in rats. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Descriptive analysis of reported adverse events associated with anti-obesity medications using FDA Adverse Event Reporting System (FAERS) databases 2013-2020. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Phase 1 First-in-Human, Single- and Multiple-Ascending Dose, and Food Effect Studies to Assess the Safety, Tolerability, and Pharmacokinetics of Presatovir for the Treatment of Respiratory Syncytial Virus Infection. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Discovery of an oral respiratory syncytial virus (RSV) fusion inhibitor (GS-5806) and clinical proof of concept in a human RSV challenge study. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of presatovir for respiratory syncytial virus after lung transplant. [2023]

14. United States pubmed.ncbi.nlm.nih.gov

Efficacy of the oral nucleoside prodrug GS-5245 (Obeldesivir) against SARS-CoV-2 and coronaviruses with pandemic potential. [2023]

15. United States pubmed.ncbi.nlm.nih.gov

Drug Resistance Assessment Following Administration of Respiratory Syncytial Virus (RSV) Fusion Inhibitor Presatovir to Participants Experimentally Infected With RSV. [2021]