INBRX-101 vs Zemaira for Emphysema

(ELEVAATE Trial)

Recruiting at 95 trial locations

Overseen By Trial Transparency email recommended (Toll free for US & Canada)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Inhibrx Biosciences, Inc

Must not be taking: A1PI, Immunoglobulins, Biologics, others

Disqualifiers: Diabetes, Cancer, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 1

Duration: 32 weeks

99 Participants Needed

Trial Summary

What is the purpose of this trial?

Phase 2 study to compare SAR447537 (INBRX-101) to plasma derived A1PI therapy in adults with AATD emphysema

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received A1PI augmentation therapy within 5 weeks before the first dose, and you must not have taken IV immunoglobulins, monoclonal antibodies, or other biologic therapies within 30 days before the trial.

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

The trial requires that you have not received A1PI augmentation therapy within 5 weeks before starting the study drug. Additionally, you should not have received IV immunoglobulins, monoclonal antibodies, or other biologic therapies within 30 days. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What data supports the idea that INBRX-101 vs Zemaira for Emphysema is an effective drug?

The available research does not provide specific data on the effectiveness of INBRX-101 vs Zemaira for Emphysema. Instead, it focuses on other treatments for chronic obstructive pulmonary disease (COPD), such as inhaled corticosteroids and single-inhaler triple therapy, which have shown benefits in reducing symptoms and hospitalizations. Without direct data on INBRX-101 or Zemaira, we cannot conclude their effectiveness for Emphysema based on the provided information. ^{1 2 3 4 5}

What safety data exists for INBRX-101 and Zemaira for emphysema treatment?

The provided research does not contain specific safety data for INBRX-101 or Zemaira in the treatment of emphysema. The studies focus on other biosimilars and treatments, such as etanercept biosimilar and rituximab biosimilar, in different conditions like psoriasis, rheumatoid arthritis, and interstitial lung disease. Therefore, no relevant safety data for INBRX-101 or Zemaira is available in the given research. ^{6 7 8 9 10}

Is the drug INBRX-101 a promising treatment for emphysema?

The information provided does not include any details about INBRX-101 or its effectiveness for emphysema. Therefore, we cannot determine if it is a promising treatment based on the given data. ^{11 12 13 14 15}

What makes INBRX-101 unique compared to other drugs for emphysema?

INBRX-101 is a novel treatment for emphysema that combines alpha-1 antitrypsin (AAT) with an antibody fragment (Fc), potentially offering a longer-lasting effect compared to standard AAT therapies like Zemaira. This unique formulation may allow for less frequent dosing, which could improve convenience and adherence for patients. ^{11 12 13 14 15}

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

Adults aged 18-80 with Alpha-1 Antitrypsin Deficiency (AATD) and emphysema can join this study. They must have a certain level of lung function and not be smokers. People with severe allergies, certain diabetes conditions, those on transplant lists or with recent infections, cancer history, heart failure or who've had similar treatments recently cannot participate.

Inclusion Criteria

I have been diagnosed with Alpha-1 Antitrypsin Deficiency.

I have emphysema due to Alpha-1 Antitrypsin Deficiency.

I am between 18 and 80 years old.

Exclusion Criteria

I am on the waiting list for a lung or liver transplant.

I have type 1 diabetes or my type 2 diabetes is not under control.

My liver is severely damaged and not functioning properly.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SAR447537 (INBRX-101) or plasma-derived A1PI therapy. SAR447537 is administered intravenously every 3 or 4 weeks, while A1PI is administered weekly.

32 weeks

Visits every 1-4 weeks depending on treatment group

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of pharmacokinetics and immunogenicity.

4 weeks

Treatment Details

Interventions

• INBRX-101
• Zemaira

Trial Overview The trial is testing INBRX-101 against Zemaira (a plasma-derived A1PI therapy) in adults with AATD-related emphysema to see which one works better for treating the condition.

Participant Groups

Group I: SAR447537 (INBRX-101) Q4W Experimental Treatment 1 Intervention

IV every 4-weeks (Q4W) and placebo (normal saline)

Group II: SAR447537 (INBRX-101) Q3W Experimental Treatment 1 Intervention

IV every 3-weeks (Q3W) and placebo (normal saline)

Group III: Zemaira (A1PI) Active Control 1 Intervention

60 mg/kg IV once weekly (QW) and placebo (normal saline)

Who Is Running the Clinical Trial?

Inhibrx Biosciences, Inc

Lead Sponsor

Trials

9

Recruited

1,700+

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Inhibrx, Inc.

Lead Sponsor

Trials

9

Recruited

1,700+

Findings from Research

In a post hoc analysis of the FORWARD study involving severe COPD patients, treatment with extrafine beclomethasone dipropionate plus formoterol fumarate (BDP-FF) resulted in a 35% reduction in exacerbation rates compared to treatment with formoterol fumarate alone.

The findings support the new GOLD 2017 recommendations, suggesting that inhaled corticosteroid (ICS) and long-acting β-agonist (LABA) therapy is a beneficial treatment option for COPD patients who experienced one exacerbation in the previous year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of extrafine beclomethasone dipropionate-formoterol fumarate in COPD patients who are not "frequent exacerbators": a post hoc analysis of the FORWARD study. Singh, D., Vezzoli, S., Petruzzelli, S., et al.[2018]

A decrease in forced expiratory volume in one second (FEV1) is linked to a significant deterioration in disease-specific health-related quality of life (HRQoL) for COPD patients, as measured by the COPD assessment test (CAT).

Experiencing at least one severe exacerbation also significantly worsens HRQoL, particularly in GOLD groups A and B, highlighting the importance of preventing exacerbations to maintain patient well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Lung Function and Exacerbations on Health-Related Quality of Life in COPD Patients Within One Year: Real-World Analysis Based on Claims Data. Stöber, A., Lutter, JI., Schwarzkopf, L., et al.[2023]

The latest GOLD guidelines recommend using inhaled corticosteroids in COPD patients who are most likely to benefit, emphasizing a more targeted approach to treatment.

Factors such as a previous asthma diagnosis, eosinophilia, elevated immunoglobulin E, and a positive bronchodilator response can help identify COPD patients who may also have asthma, guiding more effective treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recognizing asthma in patients with chronic obstructive pulmonary disease. Shedd, GC., Thompson, A., Calvert, RO.[2021]

Single-inhaler triple therapy (SITT), which combines a long-acting muscarinic antagonist, a long-acting β2-agonist, and an inhaled corticosteroid, has been shown to significantly improve lung function and reduce exacerbations and hospitalizations in patients with symptomatic COPD, based on evidence from randomized controlled trials.

While SITT is associated with a higher incidence of pneumonia due to the inhaled corticosteroid component, the overall benefits, including potential reductions in all-cause mortality, suggest that the advantages of SITT outweigh the risks, emphasizing the need for personalized treatment approaches in COPD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit/Risk Profile of Single-Inhaler Triple Therapy in COPD. Bourbeau, J., Bafadhel, M., Barnes, NC., et al.[2021]

The GOLD recommendations for COPD treatment now emphasize a combination of pulmonary function and clinical aspects, rather than relying solely on lung function, to guide treatment decisions.

There is a growing consensus among respiratory physicians that a precision medicine approach, which tailors treatment based on individual patient characteristics and inflammatory biomarkers, is essential for effective COPD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A perspective for chronic obstructive pulmonary disease (COPD) management: six key clinical questions to improve disease treatment. Contoli, M., Morandi, L., Di Marco, F., et al.[2022]

CT-P10, the first biosimilar of rituximab, has been shown to be a safe treatment alternative to the original rituximab (oRTX), with no significant differences in adverse events such as infusion-related reactions, infections, or hypogammaglobulinemia among 128 patients studied.

The study supports the rational use of biosimilars like CT-P10, demonstrating that switching from oRTX to CT-P10 does not increase the risk of adverse effects, which can help guide clinicians in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interchangeability and adverse events in originator-rituximab and its biosimilar (CT-P10) among rheumatic patients: a real-life experience. Bahap-Kara, M., Duran, E., Bayraktar-Ekincioglu, A., et al.[2023]

In a 24-week study involving 60 children with juvenile idiopathic arthritis (JIA), treatment with the etanercept biosimilar rhTNFR-Fc combined with methotrexate led to a significant reduction in disease activity, as measured by the cJADAS-10 score, which dropped from 14.66 to 2.4 (P < 0.01).

Approximately half of the patients achieved inactive disease status after 24 weeks, and improvements were also observed in symptoms like morning stiffness and joint effusions, indicating that rhTNFR-Fc is both effective and safe for treating JIA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of etanercept biosimilar rhTNFR-Fc in Chinese patients with juvenile idiopathic arthritis: An open-label multicenter observational study. Xu, X., Liu, X., Zheng, W., et al.[2022]

In a study of 50 patients with severe, progressive interstitial lung disease (ILD) treated with rituximab, there was a significant median improvement in forced vital capacity (FVC) of 6.7% after treatment, indicating potential efficacy as a rescue therapy.

Despite the benefits, there were safety concerns, as two patients experienced serious infections and ten patients died from disease progression within a median of 5.1 months post-treatment, highlighting the need for further research on safety outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in severe, treatment-refractory interstitial lung disease. Keir, GJ., Maher, TM., Ming, D., et al.[2022]

In a study involving 466 patients with moderate-to-severe plaque psoriasis, the combination of rhTNFR-Fc and methotrexate (MTX) resulted in a significantly higher rate of improvement (81.86% achieving PASI 75) compared to rhTNFR-Fc plus placebo (65.50%) at week 24.

The combination therapy was found to be effective and well-tolerated, with common side effects including upper respiratory tract infections and abnormal liver function, indicating a favorable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etanercept biosimilar (recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein) and methotrexate combination therapy in Chinese patients with moderate-to-severe plaque psoriasis: a multicentre, randomized, double-blind, placebo-controlled trial. Liu, LF., Chen, JS., Gu, J., et al.[2021]

In a study involving 214 patients with active rheumatoid arthritis, PF-05280586 showed no clinically meaningful differences in clinical response compared to both rituximab sourced from the EU and the US, as measured by the Disease Activity Score in 28 Joints (DAS28) and American College of Rheumatology (ACR) criteria.

The trial demonstrated that PF-05280586 is pharmacokinetically similar to rituximab-EU and rituximab-US, with all observed differences falling within pre-specified reference ranges, indicating its potential as a biosimilar treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative assessment of clinical response in patients with rheumatoid arthritis between PF-05280586, a proposed rituximab biosimilar, and rituximab. Williams, JH., Hutmacher, MM., Zierhut, ML., et al.[2022]

The test version of the HFA fluticasone/salmeterol inhaler showed pharmacokinetic equivalence to the reference product for fluticasone, indicating similar absorption and effectiveness in the body.

However, the test product demonstrated superior systemic bioavailability for salmeterol, suggesting it may provide better therapeutic effects without significant differences in safety outcomes like adrenal suppression or low potassium levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic bioavailability of hydrofluoroalkane (HFA) formulations of fluticasone/salmeterol in healthy volunteers via pMDI alone and spacer. Clearie, KL., Williamson, PA., Vaidyanathan, S., et al.[2021]

In a study of 1022 patients with severe COPD, budesonide/formoterol in a single inhaler demonstrated better lung function and quality of life compared to budesonide, formoterol, or placebo, while also resulting in fewer exacerbations.

The total annual healthcare costs were lower for budesonide/formoterol (€2518) compared to the monotherapies and placebo, suggesting it may be a cost-effective treatment option for managing severe COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost effectiveness of budesonide/formoterol in a single inhaler for COPD compared with each monocomponent used alone. Löfdahl, CG., Ericsson, A., Svensson, K., et al.[2018]

The 24-week INTREPID trial showed that once-daily single-inhaler triple therapy (FF/UMEC/VI) for COPD patients provided significant clinical benefits compared to multiple-inhaler triple therapy, leading to improved lung function and quality of life.

From a UK NHS perspective, FF/UMEC/VI not only resulted in better health outcomes, providing an additional 0.253 quality-adjusted life years (QALYs), but also saved £1764 per patient, making it a cost-effective treatment option for symptomatic COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Single- versus Multiple-Inhaler Triple Therapy in a UK COPD Population: The INTREPID Trial. Halpin, DMG., Kendall, R., Shukla, S., et al.[2022]

In a study of 2262 COPD patients over one year, those treated with budesonide/formoterol (BUD/FM) had significantly fewer emergency department visits (25% less) and hospitalizations (39% less) compared to those treated with fluticasone propionate/salmeterol (FP/SM).

Both treatment groups showed similar rates of COPD exacerbations and medication adherence, but the BUD/FM group required fewer doses of ipratropium bromide, indicating potentially better management of their condition with this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative effectiveness of budesonide/formoterol and fluticasone propionate/salmeterol in a 1-year, population-based, matched cohort study of patients with chronic obstructive pulmonary disease (COPD): Effect on COPD-related exacerbations, emergency department visits and hospitalizations, medication utilization, and treatment adherence. Blais, L., Forget, A., Ramachandran, S.[2015]

Symbicort, a combination inhaler for asthma and COPD, is more cost-effective than using separate inhalers for its components, budesonide and formoterol, as it leads to lower total treatment costs.

The adjustable dosing strategy of Symbicort not only maintains better asthma control with less medication but also reduces overall treatment costs compared to fixed dosing and other combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symbicort: a pharmacoeconomic review. Halpin, DM.[2018]

References

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

The efficacy of extrafine beclomethasone dipropionate-formoterol fumarate in COPD patients who are not "frequent exacerbators": a post hoc analysis of the FORWARD study. [2018]

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

Impact of Lung Function and Exacerbations on Health-Related Quality of Life in COPD Patients Within One Year: Real-World Analysis Based on Claims Data. [2023]

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

Recognizing asthma in patients with chronic obstructive pulmonary disease. [2021]

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

Benefit/Risk Profile of Single-Inhaler Triple Therapy in COPD. [2021]

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

A perspective for chronic obstructive pulmonary disease (COPD) management: six key clinical questions to improve disease treatment. [2022]

6. Italy pubmed.ncbi.nlm.nih.gov

Interchangeability and adverse events in originator-rituximab and its biosimilar (CT-P10) among rheumatic patients: a real-life experience. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of etanercept biosimilar rhTNFR-Fc in Chinese patients with juvenile idiopathic arthritis: An open-label multicenter observational study. [2022]

8. Australia pubmed.ncbi.nlm.nih.gov

Rituximab in severe, treatment-refractory interstitial lung disease. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Etanercept biosimilar (recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein) and methotrexate combination therapy in Chinese patients with moderate-to-severe plaque psoriasis: a multicentre, randomized, double-blind, placebo-controlled trial. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Comparative assessment of clinical response in patients with rheumatoid arthritis between PF-05280586, a proposed rituximab biosimilar, and rituximab. [2022]

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

Systemic bioavailability of hydrofluoroalkane (HFA) formulations of fluticasone/salmeterol in healthy volunteers via pMDI alone and spacer. [2021]

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

Cost effectiveness of budesonide/formoterol in a single inhaler for COPD compared with each monocomponent used alone. [2018]

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

Cost-Effectiveness of Single- versus Multiple-Inhaler Triple Therapy in a UK COPD Population: The INTREPID Trial. [2022]

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

Relative effectiveness of budesonide/formoterol and fluticasone propionate/salmeterol in a 1-year, population-based, matched cohort study of patients with chronic obstructive pulmonary disease (COPD): Effect on COPD-related exacerbations, emergency department visits and hospitalizations, medication utilization, and treatment adherence. [2015]

15. England pubmed.ncbi.nlm.nih.gov

Symbicort: a pharmacoeconomic review. [2018]