INBRX-101 vs Zemaira for Emphysema

(ELEVAATE Trial)

No longer recruiting at 98 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called INBRX-101 for individuals with emphysema caused by AATD, a genetic condition that leads to lung damage. Researchers aim to compare the effectiveness of INBRX-101 with an existing treatment, Zemaira, an alpha 1-proteinase inhibitor. Participants will receive INBRX-101 every three or four weeks or Zemaira weekly. Individuals diagnosed with AATD and emphysema who are currently non-smokers might be suitable for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that INBRX-101 is generally safe and well-tolerated. In earlier studies, participants received different doses without major safety issues. Some experienced mild side effects, such as headaches or minor reactions at the injection site, which are common and not serious.

INBRX-101 is a special protein designed to remain in the body longer for improved efficacy. It aims to help people with emphysema, a lung condition, by maintaining higher levels of a protective protein in their blood.

Since INBRX-101 is currently being tested in a Phase 2 study, some safety information is already available from earlier research. However, ongoing studies will provide more detailed information on its safety for people with emphysema. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for emphysema?

Most treatments for emphysema, like Zemaira, involve weekly intravenous infusions of Alpha-1 Proteinase Inhibitor (A1PI) to help manage symptoms. INBRX-101 stands out because it offers a potentially more convenient dosing schedule, with options for administration every three or four weeks instead of weekly. This extended dosing could improve patient adherence and quality of life by reducing the frequency of hospital visits. Researchers are excited because INBRX-101 could simplify treatment regimens while maintaining or even enhancing therapeutic effectiveness.

What evidence suggests that this trial's treatments could be effective for emphysema?

In this trial, participants will receive either INBRX-101 or Zemaira. A previous study showed that INBRX-101, a new protein treatment, lasts longer in the body than traditional treatments like Zemaira. INBRX-101 aims to increase levels of alpha-1 antitrypsin (AAT), a protein that protects the lungs, more effectively than current therapies. Research suggests this could help manage emphysema caused by AAT deficiency. Early findings indicate that INBRX-101 is safe and well-tolerated by patients. Overall, this treatment shows promise in improving lung function for people with this condition. ^{5 6 7 8 9}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi

Are You a Good Fit for This Trial?

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.

You do not currently smoke.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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]

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 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]

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 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)

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

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)

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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]

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]

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)

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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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05897424

Study Details | NCT05897424 | Long-term, Open-label ... Study Overview. Brief Summary. Phase 2 open label extension study to evaluate SAR447537 (INBRX-101) in adults with AATD emphysema.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11216232/

Recombinant Alpha-1 Antitrypsin–Fc Fusion Protein INBRX ... INBRX-101, a recombinant human AAT-Fc fusion protein, was designed to have a longer half-life and achieve higher AAT levels than pdAAT. Methods: ...

3. sanofi.com sanofi.com/en/media-room/press-releases/2025/2025-10-22-05-00-00-3170787

Press Release: Sanofi's efdoralprin alfa met all primary and ... Efdoralprin alfa (SAR447537, formerly known as INBRX-101) is a recombinant human AAT-Fc fusion protein being investigated as a restorative ...

4. health.ucdavis.edu health.ucdavis.edu/news/headlines/new-trial-produces-excellent-safety-results-for-rare-pulmonary-condition/2024/07

New trial produces excellent safety results for rare ... A multicenter safety study at UC Davis Health tested a protein drug (INBRX-101), developed to improve care for people with alpha-1 antitrypsin deficiency (AATD ...

5. rarediseaseadvisor.com rarediseaseadvisor.com/hcp-resource/alpha-1-antitrypsin-deficiency-clinical-trials/

Alpha-1 Antitrypsin Deficiency Clinical Trials A second phase 2, open-label extension trial (ELEVAATE OLE, NCT05897424) is assessing the long term safety and efficacy of INBRX-101 in adults ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05856331

Study of SAR447537 (INBRX-101) Compared to Plasma- ... This is a Phase 2, Double-Blind, Randomized, Active-Control, Parallel Group Study to Assess the Pharmacokinetics, Pharmacodynamics, Immunogenicity, ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38809792/

Recombinant Alpha-1 Antitrypsin-Fc Fusion Protein INBRX ... INBRX-101, a recombinant human AAT-Fc fusion protein, was designed to have a longer half-life and achieve higher AAT levels than pdAAT.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03815396

NCT03815396 | Phase 1 Study to Assess the Safety, PK ... INBRX-101 is a recombinant human alpha-1 antitrypsin (AAT) Fc fusion protein (rhAAT-Fc). Participant Group/Arm, Experimental : Part 2 Multiple Ascending Dose.

9. sanofistudies.com sanofistudies.com/cwout/CW-V9DEXS//us/en/listing/312937/study-of-sar447537-inbrx-101/

Study of SAR447537 (INBRX-101) Compared to Plasma- ... Phase 2 study to compare SAR447537 (INBRX-101) to plasma derived A1PI therapy in adults with AATD emphysema. Study Details. This is a Phase 2 ...