ALT-100mAb for Acute Respiratory Distress Syndrome

Overseen By Rebecca Nunn

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Aqualung Therapeutics Corp.

Must not be taking: Immunomodulatory biologics, JAK inhibitors

Disqualifiers: COVID-19, ECMO, COPD, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, ALT-100mAb (a monoclonal antibody), for individuals with moderate to severe acute respiratory distress syndrome (ARDS), a serious lung condition that makes breathing difficult. Researchers aim to determine the effectiveness and safety of this treatment compared to a placebo, a harmless substance with no therapeutic effect. Participants will receive different doses of the treatment to identify the most effective one. Individuals who have suddenly developed breathing problems due to ARDS, excluding those with COVID-19, and who are hospitalized, might be suitable for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like immunomodulatory biologics and high-dose corticosteroids are restricted, so it's best to discuss your specific medications with the study team.

Is there any evidence suggesting that ALT-100mAb is likely to be safe for humans?

Research shows that ALT-100mAb has undergone safety testing in people. Previous patients generally tolerated the treatment well. For instance, studies on ALT-100mAb did not find any serious side effects directly linked to the drug. In animal studies, ALT-100mAb reduced lung damage and helped maintain lung fluid balance, which is crucial for severe lung issues like ARDS. While no medication is completely without risk, current data suggests ALT-100mAb is safe. Participants in this trial can trust that thorough safety checks are in place throughout the research process. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

ALT-100mAb is unique because it targets acute respiratory distress syndrome (ARDS) with a monoclonal antibody approach, potentially offering a more precise intervention compared to traditional treatments like mechanical ventilation and corticosteroids. This drug is designed for intravenous infusion, allowing it to act directly and quickly within the bloodstream. Researchers are excited about ALT-100mAb because it could provide a targeted, rapid response to ARDS, which is crucial for improving outcomes in this severe and often life-threatening condition.

What evidence suggests that ALT-100mAb might be an effective treatment for ARDS?

Research shows that ALT-100mAb targets a protein linked to inflammation, potentially reducing lung damage. Studies in animals with ARDS (a severe lung condition) have demonstrated that this treatment helps manage lung fluid levels. Research in humans has also shown promising results for ALT-100mAb's ability to treat ARDS. In this trial, participants will receive different doses of ALT-100mAb or a placebo to further evaluate its effectiveness. These findings suggest that ALT-100mAb could effectively lessen the severity of ARDS in patients. While more information is needed, early signs are encouraging for those considering this treatment. ^{1 2 3 4 5}

Who Is on the Research Team?

Stan Miele

Principal Investigator

Aqualung Therapeutics Corp.

Are You a Good Fit for This Trial?

This trial is for adults over 18 with moderate to severe ARDS, a type of lung failure that happens quickly after an injury or infection. They must have certain blood oxygen levels and be able to start treatment within specific time frames. Pregnant women can't join, and participants need to consent to the study's rules.

Inclusion Criteria

I will receive the study treatment within 12 hours of my ARDS diagnosis and within 4 hours if I need a ventilator.

I have breathing failure not caused by heart issues or fluid buildup, with risks for ARDS.

My chest X-ray or CT scan shows unusual shadowing not caused by other known lung issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of ALT-100 mAb or placebo via IV infusion within 12 hours of ARDS diagnosis and within 4 hours of initiation of mechanical ventilation.

1 day

Dose Escalation (Part A)

Assessment of 2 doses of ALT-100 mAb in sequentially enrolled cohorts of up to 9 participants each.

Up to 29 days

Dose Expansion (Part B)

Further exploration of safety, preliminary efficacy, PK, and systemic biomarker profile of ALT-100 mAb in additional participants.

Up to 29 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of respiratory support requirements and safety outcomes.

Up to 60 days

What Are the Treatments Tested in This Trial?

Interventions

• ALT-100mAb

Trial Overview The trial tests ALT-100mAb against a placebo in patients with ARDS. It's a Phase 2a study where patients are randomly assigned treatments without knowing which one they're getting (double-blind) across multiple hospitals.

How Is the Trial Designed?

Group I: Part B (Dose Expansion) ALT-100 mAb Experimental Treatment 1 Intervention

Approximately 9 participants in each cohort in Part A, additional participants (up to 36 per dose cohort) may be enrolled into 2 dose expansion cohorts, the dose of which will be determined by the SRC. Drug: AT-02 Dosage: Will be decided by the SCR Route of Admin: Solution for IV Infusion

Group II: Part A : ALT-100 mAB (Dose Escalation) Experimental Treatment 1 Intervention

90 eligible participants will be randomized at a 2:1 ratio to receive a single dose of ALT-100 mAb. Part A will assess 2 doses of ALT-100 mAb in sequentially enrolled cohorts of up to 9 participants in each cohort. (Randomised, Double-blind) Drug: ALT-100 mAb Dosage Form: Sterile liquid, pH 5.5, Dosage: 0.4 mg/kg (Cohort 1a) and 1.0 mg/kg (Cohort 2a) Dosage Form \& Route of Admin: Solution for IV Infusion

Group III: Part A Placebo Placebo Group 1 Intervention

Part A participants with acute respiratory distress syndrome (ARDS) (Randomised, Double-blind) Dosage Form \& Route of Admin: Normal Saline Solution for IV Infusion

Who Is Running the Clinical Trial?

Aqualung Therapeutics Corp.

Lead Sponsor

Trials

2

Recruited

120+

Published Research Related to This Trial

Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) plays a significant role in the severity of acute respiratory distress syndrome (ARDS), as shown in pre-clinical models using wild-type and endothelial cell-specific knockout mice.

Neutralizing antibodies against eNAMPT effectively reduced lung inflammation and injury in ARDS models, suggesting that targeting the eNAMPT/TLR4 pathway could be a promising therapeutic strategy for treating ARDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endothelial eNAMPT amplifies pre-clinical acute lung injury: efficacy of an eNAMPT-neutralising monoclonal antibody. Quijada, H., Bermudez, T., Kempf, CL., et al.[2023]

The ALT-100 mAb, a novel biologic that neutralizes the TLR4 ligand eNAMPT, significantly reduced lung injury and acute kidney injury in a porcine model of ARDS when administered 6 hours after injury, demonstrating its potential as a therapeutic intervention.

Treatment with ALT-100 mAb preserved lung fluid balance and decreased inflammatory markers, suggesting it could address the critical need for effective therapies to reduce mortality in ARDS and ventilator-induced lung injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

eNAMPT Neutralization Preserves Lung Fluid Balance and Reduces Acute Renal Injury in Porcine Sepsis/VILI-Induced Inflammatory Lung Injury. Sammani, S., Bermudez, T., Kempf, CL., et al.[2023]

Afelimomab, an antibody fragment targeting TNF-alpha, was found to be safe and well tolerated in a phase I/II trial involving 48 sepsis patients, with predictable pharmacokinetics and no significant adverse effects related to the drug.

While afelimomab did not significantly impact 28-day mortality rates, it did lead to increased TNF levels and decreased interleukin-6 levels, suggesting a potential mechanism of action in modulating inflammatory responses in sepsis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, open-label, prospective, randomized, dose-ranging pharmacokinetic study of the anti-TNF-alpha antibody afelimomab in patients with sepsis syndrome. Gallagher, J., Fisher, C., Sherman, B., et al.[2019]

In preclinical studies involving rats and Yucatan minipigs, an eNAMPT-neutralizing monoclonal antibody (mAb) significantly reduced the severity of acute respiratory distress syndrome (ARDS) by approximately 50%, indicating its potential efficacy in treating inflammatory lung injury.

The treatment with eNAMPT mAb not only decreased inflammatory markers like IL-6 and TNFα but also corrected dysregulated signaling pathways (NFkB and Akt/mTORC2), suggesting a mechanism of action that targets the eNAMPT/TLR4 inflammatory pathway to mitigate ARDS-related lung damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

eNAMPT neutralization reduces preclinical ARDS severity via rectified NFkB and Akt/mTORC2 signaling. Bermudez, T., Sammani, S., Song, JH., et al.[2023]

In a study of 446 ARDS patients, neuromuscular blockade (NMB) was linked to significant reductions in biomarkers indicating lung injury and inflammation, specifically surfactant protein-D, von Willebrand factor, and interleukin-8, particularly in patients with lower oxygen levels (P/F ratio ≤ 120) receiving low tidal volume ventilation.

The effectiveness of NMB in reducing these harmful biomarkers was not observed in patients with higher oxygen levels (P/F ratio > 120) or those receiving high tidal volume ventilation, suggesting that the benefits of NMB may depend on the severity of hypoxemia and the ventilation strategy used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromuscular blockade is associated with the attenuation of biomarkers of epithelial and endothelial injury in patients with moderate-to-severe acute respiratory distress syndrome. Sottile, PD., Albers, D., Moss, MM.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05938036

Study of Safety and Efficacy of ALT-100mAb in Participants ... PUERTA is a Phase 2a, randomized, double-blind, placebo-controlled study in adults with moderate to severe ARDS consequent to sepsis, septic shock, trauma, ...

2. reporter.nih.gov reporter.nih.gov/search/19qGcVuv3Ueft6eN_LmXVQ/project-details/10581161

the PUERTA Trial Both ALT-100 mAb safety and efficacy will be assessed in the proposed R-44 PUERTA trial, a randomized Phase IIA clinical trial, as well as the development of an ...

3. withpower.com withpower.com/trial/phase-2-respiratory-distress-syndrome-6-2023-42578

ALT-100mAb for Acute Respiratory Distress Syndrome Research shows that ALT-100mAb, which targets a protein involved in inflammation, can reduce lung injury and improve lung fluid balance in animal models of ARDS ...

4. firstwordpharma.com firstwordpharma.com/story/5807172

Treatment with Aqualung Therapeutics ALT-100 mAb The compelling results of our human biomarker and genetic studies in subjects with ARDS combined with the dramatic efficacy of the ALT-100 mAb ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05426746

First-In-Human Study to Investigate the Safety, Tolerability ... This study will collect data to evaluate safety and tolerability, Pharmacokinetics of ALT-100, Pharmacodynamics of ALT-100 and determine if Anti-drug Antibodies ...