Verekitug for Severe Asthma

Recruiting at 153 trial locations

Overseen By Upstream Bio Clinical Trials Information (Privacy Notice: https://www.upstreambio.com/privacy)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Upstream Bio Inc.

Must be taking: Inhaled corticosteroids

Must not be taking: Biologics, Allergen immunotherapy

Disqualifiers: Recent hospitalization, Smoking, Infections, others

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

Compensation: Varies

Number of Visits: 12

Duration: Up to 60 weeks with a minimum of 24 weeks

436 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new injectable medication, verekitug (UPB-101), on adults with severe asthma to see if it can reduce asthma attacks and improve breathing.

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

The trial does not specify if you need to stop your current medications, but it does require that your oral corticosteroid dose is stable for at least 2 weeks before starting. If you've used certain biologics, a washout period (time without taking those medications) may be needed.

What data supports the effectiveness of the drug Verekitug (UPB-101) for severe asthma?

The research mentions that similar treatments, like tezepelumab and omalizumab, have shown effectiveness in improving lung function and reducing symptoms in patients with severe asthma. This suggests that Verekitug (UPB-101), which may work in a similar way, could also be effective for severe asthma. ^{1 2 3 4 5}

What makes the drug Verekitug (UPB-101) unique for treating severe asthma?

Verekitug (UPB-101) is unique because it may involve a novel mechanism of action or formulation not detailed in the provided research, as there is no direct information available about its specific properties or how it differs from existing treatments for severe asthma. ^{2 6 7 8 9}

Research Team

James C Lee, MD

Principal Investigator

Upstream Bio

Eligibility Criteria

This trial is for adults aged 18-75 with severe asthma, who've had an exacerbation in the past year and are on medium to high dose inhalers plus another controller medication. They must have a certain level of asthma control and lung function, agree to use contraception, and be able to follow the study's procedures.

Inclusion Criteria

I have been on medium or high dose asthma inhalers for 3 months, and if on a medium dose, I've also used another asthma control medicine.

You have signed and received a copy of the document that explains the study and your rights.

My lung function improves with a bronchodilator.

Timeline

Screening/Run-In

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive verekitug (UPB-101) or placebo subcutaneously at varying doses every 12 or 24 weeks

Up to 60 weeks with a minimum of 24 weeks

Injections every 12 or 24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

Treatment Details

Interventions

• Verekitug (UPB-101)

Trial Overview The VALIANT study tests Verekitug (UPB-101) against a placebo in severe asthma patients. It measures how well it prevents worsening of symptoms, improves lung function and overall control of asthma compared to not receiving the active drug.

Participant Groups

Group I: Verekitug (UPB-101): 400 mg Q24W / Placebo Experimental Treatment 2 Interventions

Participants will receive 2.0 mL of verekitug (UPB-101) formulated solution (containing 400 mg of verekitug \[UPB-101\]) and 0.5 mL of placebo subcutaneously in two separate injections every 24 weeks up to Week 48. Participants will also receive 2 mL and 0.5 mL of placebo subcutaneously in two separate injections at Weeks 12 and 36 visits.

Group II: Verekitug (UPB-101): 100 mg Q24W / Placebo Experimental Treatment 2 Interventions

Participants will receive 0.5 mL of verekitug (UPB-101) formulated solution (containing 100 mg of verekitug \[UPB-101\]) and 2.0 mL of placebo subcutaneously in two separate injections every 24 weeks up to Week 48. Participants will also receive 2 mL and 0.5 mL of placebo subcutaneously in two separate injections at Weeks 12 and 36 visits.

Group III: Verekitug (UPB-101): 100 mg Q12W / Placebo Experimental Treatment 2 Interventions

Participants will receive 0.5 milliliter (mL) of verekitug (UPB-101) formulated solution (containing 100 milligrams \[mg\] of verekitug \[UPB-101\]) and 2.0 mL of placebo subcutaneously in two separate injections every 12 weeks up to Week 48.

Group IV: Placebo Placebo Group 1 Intervention

Participants will receive 0.5 mL of matching placebo and 2.0 mL of matching placebo subcutaneously in two separate injections every 12 weeks up to Week 48.

Who Is Running the Clinical Trial?

Upstream Bio Inc.

Lead Sponsor

Trials

4

Recruited

570+

Findings from Research

In the phase 3 NAVIGATOR study involving patients aged 12-80 with severe asthma, tezepelumab significantly improved various lung function parameters, including pre-bronchodilator FEV1 and forced vital capacity (FVC), compared to placebo over 52 weeks.

Improvements in lung function were observed as early as 1-2 weeks and were particularly pronounced in patients with a shorter disease duration and specific baseline lung function characteristics, indicating tezepelumab's efficacy in managing severe asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Tezepelumab on Lung Function in Patients With Severe, Uncontrolled Asthma in the Phase 3 NAVIGATOR Study. Menzies-Gow, A., Ambrose, CS., Colice, G., et al.[2023]

In a study of 261 steroid-naive patients with severe persistent asthma, zafirlukast (20 mg twice daily) significantly improved lung function measures, including FEV1 and peak expiratory flow (PEF), compared to placebo.

Zafirlukast also reduced nighttime awakenings and daytime asthma symptoms, demonstrating its efficacy as a monotherapy for managing severe asthma symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic effect of zafirlukast as monotherapy in steroid-naive patients with severe persistent asthma. Kemp, JP., Minkwitz, MC., Bonuccelli, CM., et al.[2021]

Omalizumab, a humanized monoclonal antibody targeting IgE, is effective in significantly reducing IgE levels in patients with severe asthma, particularly those who remain symptomatic despite high-dose inhaled corticosteroids and long-acting beta-agonists.

The strongest evidence for omalizumab's efficacy is observed in patients experiencing frequent severe asthma exacerbations, highlighting its role as a targeted therapy for this specific group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-IgE and chemotherapy: a critical appraisal of treatment options for severe asthma. Walters, EH., Walters, JA., Wood-Baker, R.[2019]

Inhaled corticosteroids (ICS) are the primary treatment for asthma, but they do not alter the disease's natural progression, highlighting the need for new therapies that target specific inflammatory pathways.

A review of 19 recent Phase I and II randomized controlled trials identified 16 classes of novel asthma treatments, including biologics targeting interleukins and other pathways, showing promise in improving lung function, but larger studies are needed to confirm their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational Treatments in Phase I and II Clinical Trials: A Systematic Review in Asthma. Calzetta, L., Aiello, M., Frizzelli, A., et al.[2022]

In a post hoc analysis of the QUEST study involving 530 Latin American patients with uncontrolled asthma, dupilumab significantly reduced the annualized rate of severe asthma exacerbations by 52.7% compared to placebo.

Dupilumab also improved lung function, as indicated by a 0.15 L increase in pre-bronchodilator FEV1 at week 12, while maintaining a safety profile consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab efficacy and safety in Latin American patients with uncontrolled, moderate-to-severe asthma: phase 3 LIBERTY ASTHMA QUEST study. Maspero, JF., Cardona, G., Schonffeldt, P., et al.[2023]

Current therapies for asthma work well for most patients, but there is a significant need for safer and more effective treatments for those with severe, refractory asthma, which is the focus of ongoing research.

Recent clinical trials of new biologic therapies targeting the T-helper 2 allergic pathway have not met expectations, indicating the need for better-targeted approaches for specific subpopulations of severe asthma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologic therapy for atopic asthma and beyond. Caruso, M., Crisafulli, E., Lizzio, R., et al.[2013]

Dupilumab, a monoclonal antibody that targets the IL-4 receptor, has shown significant efficacy in treating severe uncontrolled bronchial asthma, as demonstrated in pivotal clinical trials such as DRI12544, QUEST, and VENTURE.

The use of dupilumab is supported by Federal Clinical Guidelines for asthma management, making it a recommended treatment option for patients experiencing frequent exacerbations, highlighting its clinical and economic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Experience of using dupilumab in the treatment of severe asthma]. Ignatova, GL., Antonov, VN., Makarova, EA., et al.[2022]

Inhaled verlukast (8 mg) significantly improved lung function (FEV1) in 12 asthmatic subjects, showing a notable increase compared to placebo, particularly peaking at 2 hours post-inhalation.

Verlukast also enhanced the bronchodilator response to salbutamol, indicating its potential as a beneficial treatment for asthma, although the lower dose (2 mg) did not provide additional effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bronchodilator properties of an inhaled leukotriene D4 antagonist (verlukast--MK-0679) in asthmatic patients. Lammers, JW., Van Daele, P., Van den Elshout, FM., et al.[2019]

In a study of 18 severe asthma patients treated with dupilumab for 12 months, significant improvements were observed in asthma control, with the Asthma Control Test (ACT) score increasing from 15.7 to 22.4, and a complete cessation of oral corticosteroid use in all patients.

Dupilumab treatment also led to a notable reduction in asthma exacerbations from an average of 2 to 0, and an increase in lung function (FEV1%) from 73.5% to 87.1%, confirming its effectiveness in a real-world setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Experience with Dupilumab in Severe Asthma: One-Year Data from an Italian Named Patient Program. Campisi, R., Crimi, C., Nolasco, S., et al.[2022]

References

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

Effect of Tezepelumab on Lung Function in Patients With Severe, Uncontrolled Asthma in the Phase 3 NAVIGATOR Study. [2023]

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

Therapeutic effect of zafirlukast as monotherapy in steroid-naive patients with severe persistent asthma. [2021]

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

Anti-IgE and chemotherapy: a critical appraisal of treatment options for severe asthma. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Investigational Treatments in Phase I and II Clinical Trials: A Systematic Review in Asthma. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Dupilumab efficacy and safety in Latin American patients with uncontrolled, moderate-to-severe asthma: phase 3 LIBERTY ASTHMA QUEST study. [2023]

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

Biologic therapy for atopic asthma and beyond. [2013]

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Experience of using dupilumab in the treatment of severe asthma]. [2022]

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

Bronchodilator properties of an inhaled leukotriene D4 antagonist (verlukast--MK-0679) in asthmatic patients. [2019]

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

Real-World Experience with Dupilumab in Severe Asthma: One-Year Data from an Italian Named Patient Program. [2022]