IC14 for Heart Failure

Not currently recruiting at 1 trial location

Overseen By Ben Van Tassell, PharmD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Implicit Bioscience

Must be taking: Loop diuretics

Must not be taking: Immunosuppressives, Anti-inflammatories

Disqualifiers: Acute coronary syndromes, Uncontrolled hypertension, Active infection, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the drug IC14 (also known as Atibuclimab, an anti-CD14 antibody) can help treat adults hospitalized with acute decompensated heart failure (ADHF). Researchers aim to determine the safety of IC14 and its effects on the heart and disease markers in the bloodstream. Participants will receive IC14 through an IV and attend several follow-up visits to monitor their health. This trial may suit patients hospitalized with breathing difficulties due to heart failure and a history of reduced heart function. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to the early-stage development of a potential new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have used immunosuppressive or anti-inflammatory drugs recently, you may not be eligible to participate.

Is there any evidence suggesting that the drug IC14 is likely to be safe for humans?

Research has shown that atibuclimab (IC14) is being tested for safety in treating heart conditions. In earlier studies, researchers administered IC14 to people with various heart issues, focusing on the drug's safety when given directly into a vein through an IV.

In one study involving patients with a different heart condition, the drug was generally well-tolerated. Some serious health events occurred, but they resulted from the disease itself, not the drug. Another study on a condition unrelated to heart failure showed an increase in certain cells after taking IC14, but no unexpected side effects from the drug were observed.

Since this trial is in its early stages, it primarily aims to assess the safety of IC14 for people with acute decompensated heart failure. This phase focuses on ensuring the drug doesn't cause harmful effects, and so far, results appear promising based on earlier findings. ^{1 2 3 4 5}

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

Unlike the standard of care for heart failure, which typically includes medications like ACE inhibitors, beta-blockers, and diuretics, atibuclimab is an experimental treatment that works differently by targeting immune responses. Atibuclimab is a monoclonal antibody administered intravenously, which could provide a new way to manage heart failure. Researchers are excited about this potential treatment because it might offer a more targeted approach, reducing inflammation associated with heart failure, and could lead to quicker improvements in patient outcomes compared to traditional therapies.

What evidence suggests that IC14 might be an effective treatment for heart failure?

Research has shown that high levels of a substance called soluble CD14 are linked to worse outcomes in heart failure. Atibuclimab, also known as IC14, is the treatment under study in this trial to target CD14. Early studies with a similar treatment showed it can reduce heart damage by blocking CD14. In animal studies, this approach helped prevent heart problems and damage. These findings suggest that atibuclimab might improve heart function in people with acute decompensated heart failure (ADHF). ^{1 2 4 5 6}

Who Is on the Research Team?

Antonio Abbate, MD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

This trial is for adults hospitalized with acute decompensated heart failure (ADHF). Participants must be currently admitted for ADHF to qualify. Specific inclusion and exclusion criteria details are not provided, but typically these would outline the health status and other conditions that either qualify or disqualify a person from participating.

Inclusion Criteria

Patients must be symptomatic for moderate to severe dyspnea, have received or scheduled to receive intravenous loop diuretics, be at least 21 years old, willing to provide informed consent, have screening plasma C-reactive protein levels >3 mg/L, and use effective contraception if of childbearing potential

I was hospitalized for worsening heart failure, experiencing shortness of breath, and have a weak heart pump.

Exclusion Criteria

I do not have severe heart failure, major health issues, recent surgeries, or use medications that could interfere with the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single intravenous infusion of IC14 and are monitored for safety and efficacy

1 day

1 visit (in-person)

Monitoring

Participants are monitored in the hospital or clinic for safety and efficacy, including biomarker and pharmacokinetic assessments

10 days

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a phone call assessment

3 months

1 visit (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Atibuclimab

Trial Overview The trial is testing atibuclimab (IC14), administered once via IV infusion, to treat ADHF. It aims to assess the safety of IC14, its levels in the bloodstream post-treatment, its effect on disease markers in blood, and how it impacts heart failure measures. There's no placebo comparison; all participants receive IC14.

How Is the Trial Designed?

Group I: IC14 (atibuclimab) Experimental Treatment 1 Intervention

20 mg/kg intravenously once at baseline

Atibuclimab is already approved in United States for the following indications:

Approved in United States as Atibuclimab for:

• Acute Decompensated Heart Failure (clinical trial phase, not yet approved)

Who Is Running the Clinical Trial?

Implicit Bioscience

Lead Sponsor

Trials

12

Recruited

140+

Virginia Commonwealth University

Collaborator

Trials

732

Recruited

22,900,000+

University of Virginia

Collaborator

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

The study explored various engineered anti-Fn14 antibody variants, revealing that those with four or more binding sites effectively activate the alternative NFκB pathway and enhance TNF-induced cell death, similar to the natural ligand TWEAK.

Certain antibody constructs, particularly IgG1-scFv fusion proteins, were found to preferentially activate the classical NFκB pathway, indicating potential for developing targeted therapies that harness Fn14 signaling without unwanted side effects from Fcγ receptor interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-based soluble and membrane-bound TWEAK mimicking agonists with FcγR-independent activity. Zaitseva, O., Hoffmann, A., Löst, M., et al.[2023]

XmAb5871 effectively suppresses B cell activation by coengaging the Fcγ receptor IIb (FcγRIIb) and the B cell antigen receptor (BCR), demonstrating its potential as a therapeutic strategy for rheumatoid arthritis (RA).

The study found that XmAb5871's efficacy in inhibiting B cell activation was consistent across patients with RA and healthy donors, indicating that it may work effectively regardless of the presence of rheumatoid factor or anti-citrullinated protein antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppression of rheumatoid arthritis B cells by XmAb5871, an anti-CD19 antibody that coengages B cell antigen receptor complex and Fcγ receptor IIb inhibitory receptor. Chu, SY., Yeter, K., Kotha, R., et al.[2017]

The first-in-human trial of the CD28-specific monoclonal antibody TGN1412 led to severe cytokine release syndrome, highlighting potential safety concerns with this treatment.

The study found that the binding of TGN1412 to different Fcγ receptors does not predict T-cell activation; specifically, weaker binding to certain receptors resulted in stronger T-cell proliferation, suggesting that the design of therapeutic monoclonal antibodies should consider these complex interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Fcγ receptors compete for TGN1412 binding that determines the antibody's effector function. Dudek, S., Weißmüller, S., Anzaghe, M., et al.[2020]

Immune checkpoint inhibitors (ICIs) significantly improve survival rates in patients with advanced cancers, but they can also lead to serious cardiovascular adverse events (CVAEs), with myocarditis being the most common.

Management of severe myocarditis caused by ICIs requires immediate treatment with high-dose corticosteroids and stopping the ICI therapy, highlighting the need for physicians to be vigilant about these potential toxicities as ICI use becomes more widespread.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Toxicities of Immune Checkpoint Inhibitors: JACC Review Topic of the Week. Ball, S., Ghosh, RK., Wongsaengsak, S., et al.[2020]

Immune checkpoint inhibitors (ICIs), particularly those targeting PD-1 and PD-L1, have transformed cancer treatment but are associated with serious immune-related adverse events (IRAEs), including myocarditis, which can complicate patient care.

Current management of IRAEs typically involves high-dose corticosteroids and discontinuation of ICIs, which can be detrimental since these therapies are often the last resort for advanced cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors: Cardiotoxicity in Pre-clinical Models and Clinical Studies. Xu, S., Sharma, UC., Tuttle, C., et al.[2021]

In heart failure (HF) models, immune checkpoint ligands like sPD-L1, sPD-L2, and galectin-9 were found to be elevated and associated with disease severity, indicating their potential role in HF pathogenesis.

Higher serum levels of sPD-L1 and galectin-9 were linked to an increased risk of HF hospitalization and all-cause mortality, suggesting they could serve as important prognostic biomarkers in HF patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating immune checkpoints predict heart failure outcomes. Screever, EM., Yousif, LIE., Moslehi, JJ., et al.[2023]

Immune checkpoint inhibitors (ICIs) have shown strong anti-tumor effects in cancer treatment by preventing tumor cells from inhibiting T-cell activation, but they can also lead to serious immune-related adverse events (irAEs), particularly affecting the cardiovascular system.

The review highlights that while ICIs can induce life-threatening conditions like myocarditis and cardiomyopathy due to increased autoimmunity and T-cell activity, understanding the mechanisms of IC function in cardiovascular disease may help identify therapeutic targets to prevent or treat these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of immune checkpoints in cardiovascular disease. Yousif, LI., Tanja, AA., de Boer, RA., et al.[2022]

Immune checkpoint inhibitors (ICIs) effectively activate the immune system against various cancers, but they can also lead to serious immune-related adverse events (irAEs), particularly affecting the heart, such as myocarditis.

The study identifies potential immune mechanisms behind cardiac irAEs, including the recruitment of T cells, autoantibody-mediated damage, and inflammatory cytokines, suggesting that factors like cancer severity and the release of self-antigens from cardiac tissues may contribute to this cardiotoxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of the Mechanisms Involved in Immune Checkpoint Inhibitors Cardiotoxicity and Challenges to Improve Clinical Safety. Rubio-Infante, N., Ramírez-Flores, YA., Castillo, EC., et al.[2022]

The review highlights advancements in chronic heart failure treatment from 2014, focusing on improved medication regimens, including beta blockers and mineralocorticoid receptor antagonists, which are essential for managing this common disease.

New pharmacological developments, such as angiotensin receptor neprilysin inhibition, are discussed as promising options for enhancing heart failure therapy, alongside insights into managing comorbidities like atrial fibrillation and hyperkalemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Update on therapy of chronic heart failure. Innovations and studies from last year]. Ewen, S., Linicus, Y., Böhm, M.[2018]

Immune checkpoint inhibitors (ICIs), while effective in treating tumors, can lead to serious immune-related adverse events (irAEs), including rare but potentially lethal cardiotoxicity.

PD-1 and PD-L1 inhibitors can affect the cardiovascular system due to their expression in heart cells, highlighting the need for careful monitoring and management of heart-related side effects in patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiotoxicity associated with immune checkpoint inhibitors: Current status and future challenges. Gan, L., Liu, D., Ma, Y., et al.[2022]

Monoclonal antibody 14C5 specifically binds to the vascular integrin alphavbeta5, which is expressed in various epithelial cancer cell lines, indicating its potential as a targeted therapy.

In tissue samples, 14C5 antigen was found in 50% of colon cancer tumors and in a subset of non-small cell lung cancers, suggesting that mAb 14C5 could be useful for identifying patients who may benefit from anti-alphavbeta5 therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibody 14C5 targets integrin alphavbeta5. Burvenich, I., Schoonooghe, S., Vervoort, L., et al.[2020]

The immune system plays a crucial role in heart failure, yet it is often overlooked as a target for treatment, which could limit the effectiveness of current therapies.

Current heart failure treatments have various immunomodulatory effects beyond their primary actions, suggesting that understanding these effects could help develop new immunomodulatory therapies tailored for specific patient subpopulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulation and immunopharmacology in heart failure. Markousis-Mavrogenis, G., Baumhove, L., Al-Mubarak, AA., et al.[2023]

Celacade treatment in rats significantly reduced the production of transforming growth factor beta-1 in the heart after a myocardial infarction, indicating its potential to modulate inflammatory responses during acute heart injury.

While Celacade did not prevent chronic cardiac dilation following myocardial infarction, it successfully restored the heart's ability to contract more forcefully and reduced diastolic dysfunction, suggesting it may improve heart function post-injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of therapy using the Celacade system on structural and functional cardiac remodelling in rats following myocardial infarction. Zhang, ML., Mei, J., Archer, LA., et al.[2021]

The recombinant human IgG 3A2 specifically inhibits MMP-14, a matrix metalloproteinase involved in tumor growth and metastasis, without affecting similar MMPs, showcasing its potential as a targeted cancer therapy.

In a breast cancer model, IgG 3A2 significantly reduced primary tumor growth and metastatic spread to the lungs and liver by 94%, while also inhibiting the proliferation of tumor stem cells, indicating its effectiveness in preventing cancer progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of a novel camelid-inspired human antibody demonstrates the importance of MMP-14 to cancer stem cell function in the metastatic process. Chen, KE., Chen, C., Lopez, T., et al.[2019]

In a study of 5217 older adults over 13.6 years, higher levels of soluble CD14 (sCD14) were significantly associated with an increased risk of developing heart failure (HF), with a hazard ratio of 1.56 per doubling of sCD14, indicating a stronger association than other inflammatory markers like hsCRP and IL-6.

The association between sCD14 and heart failure was specifically noted in cases of heart failure with preserved ejection fraction (HFpEF), suggesting that sCD14 could be a potential biomarker for predicting this subtype of heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Soluble CD14 and Risk of Heart Failure and Its Subtypes in Older Adults. Al-Kindi, SG., Buzkova, P., Shitole, SG., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06556810

IC14 for Treatment of Acute Decompensated Heart Failure The goal of this clinical trial is to learn if drug atibuclimab (IC14) works to treat adults hospitalized with acute decompensated heart failure (ADHF).

2. withpower.com withpower.com/trial/ic14-for-heart-failure-cf5e9

IC14 for Heart Failure · Info for Participants Elevated levels of soluble CD14 are linked to poor outcomes in heart failure, indicating that targeting CD14 with treatments like Atibuclimab might help ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06678074/pilot-study-of-ic14-atibuclimab-an-anti-cd14-monoclonal-antibody-to-treat-stemi

Pilot Study of IC14 (Atibuclimab), an Anti-CD14 ... The goal is to learn if this treatment improves some measures of heart function and inflammation. The study treatment patients will be compared ...

4. jacc.org jacc.org/doi/10.1016/j.jacbts.2025.101393

CD14 Blockade Modulates Macrophage-Mediated ... Anti-CD14 antibody therapy with a murine analogue of atibuclimab mitigated post-acute progression of left ventricular dysfunction, ...

5. clinicaltrial.be clinicaltrial.be/en/details/426537?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

IC14 (Atibuclimab) in Arrhythmogenic Cardiomyopathy - Cli... In preclinical studies, anti-CD14 treatment prevented the development of ventricular dysfunction and cardiac damage in a mouse model of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36533976/

Safety/activity of anti-CD14 antibody IC14 (atibuclimab) in ALS Three participants died due to disease progression. Monocyte CD14 RO increased for all participants after IC14 infusion. One individual required more frequent ...