ELA026 for Hemophagocytic Lymphohistiocytosis

Recruiting at 25 trial locations

Overseen By Clinical Trials

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Electra Therapeutics Inc.

Must not be taking: HLH therapies

Disqualifiers: Primary HLH, Severe organ dysfunction, 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

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

Compensation: Varies

Number of Visits: Unknown

156 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, ELA026, for individuals with secondary hemophagocytic lymphohistiocytosis (sHLH), a rare and serious immune condition. sHLH causes the immune system to overreact, resulting in severe inflammation. The trial aims to assess the safety and effectiveness of ELA026 in managing this condition. Individuals diagnosed with sHLH who are either new to treatment or have not responded well to previous treatments may be suitable candidates. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants an opportunity to contribute to significant advancements in sHLH treatment.

Do I have to stop taking my current medications for this trial?

The trial requires that you stop ongoing administration of any therapies used to treat HLH, except for dexamethasone. The protocol does not specify about other medications, so it's best to discuss with the trial team.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but ongoing administration of any therapies used to treat HLH (except dexamethasone) is not allowed.

Is there any evidence suggesting that ELA026 is likely to be safe for humans?

Research has shown that ELA026 is safe for people with secondary hemophagocytic lymphohistiocytosis (sHLH). In earlier studies, all patients responded positively to the treatment, and their survival rates improved. The treatment was generally well-tolerated, with no major safety issues reported. These findings suggest that ELA026 is safe to use, and any side effects can be managed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ELA026 for treating Hemophagocytic Lymphohistiocytosis (HLH) because it offers a novel approach compared to current therapies like dexamethasone, etoposide, and cyclosporine. Unlike these standard treatments, which target inflammation broadly, ELA026 is designed to more precisely modulate immune responses, potentially reducing harmful immune activity without broadly suppressing all immune functions. Additionally, ELA026 can be administered both intravenously and subcutaneously, offering flexibility in treatment delivery. This targeted action and flexible administration could lead to better outcomes and fewer side effects for patients with HLH.

What evidence suggests that ELA026 might be an effective treatment for hemophagocytic lymphohistiocytosis?

Research shows that ELA026, which participants in this trial may receive, has promising results for treating secondary hemophagocytic lymphohistiocytosis (sHLH), a serious immune disorder. Previous studies reported a 100% response rate in patients with cancer-related HLH (a type of sHLH), with significant improvements in survival rates. ELA026 targets and reduces certain immune cells that cause inflammation, helping to quickly control inflammation and improve patient outcomes. Early evidence suggests that ELA026 effectively manages symptoms and improves survival in this challenging condition. ^{1 2 3 4 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Electra Therapeutics Inc.

Are You a Good Fit for This Trial?

This trial is for people aged 12 and older diagnosed with secondary hemophagocytic lymphohistiocytosis (HLH), a severe immune activation condition. Participants can be treatment-naive or have relapsed/refractory HLH, must meet specific diagnostic criteria, and be hospitalized. Those with primary HLH, uncontrolled conditions, recent investigational treatments or stem cell transplants are excluded.

Inclusion Criteria

I was 12 years or older when diagnosed with HLH.

I was diagnosed with HLH at an age that fits the study's requirements.

I have not received any treatment for my condition.

Exclusion Criteria

I had a stem cell transplant less than 100 days ago.

Any other significant concurrent, uncontrolled medical condition that in the opinion of the Investigator contraindicates participation in this study

I have received CAR T-Cell therapy within the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment (Part 1)

Participants receive ELA026 in a dose-escalating cohort followed by fixed dose cohorts over 12 weeks

12 weeks

Weekly visits for maintenance doses

Treatment (Part 2)

Participants receive ELA026 with a priming dose followed by twice weekly maintenance doses

12 weeks

Twice weekly visits for maintenance doses

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ELA026

Trial Overview The study tests ELA026, an antibody aimed at reducing inflammation caused by myeloid and T cells in patients with secondary HLH. It evaluates the safety and effectiveness of this drug as well as how it's processed by the body.

How Is the Trial Designed?

Group I: Part 2 ELA026 Experimental Treatment 1 Intervention

Cohort A and Cohort B: priming dose: 0.1 mg/kg IV on Day 1; loading dose 0.3 mg/kg IV on Days 2- 4, followed by twice weekly maintenance doses of 0.5 mg/kg (IV/SC) from Day 8 to Day 81.

Group II: Part 1 ELA026 Experimental Treatment 1 Intervention

Cohort 1: Single dose escalation up to 3.0 mg/kg IV or SC. Cohort 2: priming dose: 0.1 mg/kg IV on Day 1; 0.3 mg/kg IV on Day 2 - 4, followed by weekly maintenance doses of 1 mg/kg IV/SC from Day 8 to Day 81. Cohort 3: priming dose: 0.1 mg/kg IV on Day 1; 0.3 mg/kg IV on Days 2 - 4, followed by twice weekly maintenance doses of 0.5 mg/kg IV/SC from Day 8 to Day 81.

ELA026 is already approved in United States for the following indications:

Approved in United States as ELA026 for:

Who Is Running the Clinical Trial?

Electra Therapeutics Inc.

Lead Sponsor

Trials

2

Recruited

250+

Published Research Related to This Trial

In a study of 41 patients diagnosed with hemophagocytic lymphohistiocytosis (HLH) at the University of Arkansas, the overall mortality rate was high at 54%, highlighting the severity of this disorder.

Patients with malignancy-related HLH had a significantly worse prognosis, with a mortality rate of 73.33%, compared to 34.62% for those without malignancies, indicating that underlying conditions greatly affect outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemophagocytic lymphohistiocytosis in adults. Pandey, Y., Atwal, D., Konda, M., et al.[2020]

A 9-month-old boy with hemophagocytic lymphohistiocytosis (HLH) underwent successful allogeneic stem cell transplantation (SCT) using a reduced-intensity conditioning regimen, leading to normal recovery and no signs of HLH or graft-versus-host disease (GVHD) after 20 months.

The study suggests that reduced-intensity conditioning for SCT may be a safer and effective option for treating HLH in children, as it minimizes toxicity while still achieving successful outcomes without the need for complete myeloablation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful father-to-son stem cell transplantation in a child with hemophagocytic lymphohistiocytosis using a reduced-intensity conditioning regimen. Gonzalez-Llano, O., Jaime-Pérez, J., Cantu-Rodríguez, O., et al.[2013]

Tocilizumab, when used in combination with methotrexate (MTX) for treating rheumatoid arthritis (RA), is associated with a statistically significant increased risk of adverse events (AEs), particularly at the 8 mg/kg dosage, with an odds ratio of 1.53 compared to controls.

While there is a higher risk of infections in patients receiving the 8 mg/kg combination therapy (odds ratio of 1.30), the study found no increased incidence of malignancy, tuberculosis reactivation, or hepatitis, indicating a specific safety profile that requires monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab: a systematic literature review and meta-analysis of randomized controlled trials. Campbell, L., Chen, C., Bhagat, SS., et al.[2022]

In a pooled analysis of 4170 patients from six trials, belimumab showed similar safety and efficacy profiles in older adults (≥65 years) with systemic lupus erythematosus (SLE) compared to the overall patient population, indicating it can be a viable treatment option for this age group.

While older adults had lower disease activity but more organ damage, the rates of serious adverse events were comparable between older adults and the overall population, suggesting that belimumab is generally safe for use in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of belimumab in older adults with SLE: results of an integrated analysis of clinical trial data. D'Cruz, D., Eriksson, G., Green, Y., et al.[2023]

In a retrospective study of 66 patients with hemophagocytic lymphohistiocytosis (HLH), the overall mortality rate was 45.9%, highlighting the severe prognosis associated with this rare syndrome.

The study identified lymphoma as the most common cause of HLH, with advanced age and the presence of severe cytopenias linked to poorer outcomes, confirming and expanding upon existing literature on the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hemophagocytic lymphohistiocytosis: A retrospective analysis of 66 patients]. Thiebaut, L., Pasquier, G., Theret, S., et al.[2023]

Adalimumab has been shown to be generally safe and well tolerated in patients with rheumatoid arthritis, based on safety data from over 10,000 patients and 12,506 patient-years of exposure in clinical trials.

The rate of serious infections was consistent with previous reports, and after implementing tuberculosis screening, the incidence of TB cases decreased significantly, indicating effective monitoring and management of potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety analyses of adalimumab (HUMIRA) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis. Schiff, MH., Burmester, GR., Kent, JD., et al.[2022]

In a study of 343 patients with acute myeloid leukemia undergoing intensive chemotherapy, 9.3% developed hemophagocytic lymphohistiocytosis (HLH), which is linked to severe infections and characterized by symptoms like fever and very high ferritin levels.

Patients with HLH had a significantly shorter median overall survival of 14.9 months compared to 22.1 months for those without HLH, highlighting the condition's serious impact on treatment outcomes and the need for prompt diagnosis and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemophagocytic syndrome in patients with acute myeloid leukemia undergoing intensive chemotherapy. Delavigne, K., Bérard, E., Bertoli, S., et al.[2021]

Alemtuzumab, natalizumab, and fingolimod are the most effective immunotherapies for preventing relapses in patients with relapsing-remitting multiple sclerosis, although their impact on preventing disability worsening is uncertain.

Fingolimod carries a high risk of treatment discontinuation due to adverse events, highlighting the importance of monitoring for side effects in patients undergoing this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Immunotherapies With Outcomes in Relapsing-Remitting Multiple Sclerosis. Tramacere, I., Del Giovane, C., Filippini, G.[2016]

The paper advocates for the creation of a comprehensive reference database to track rare but serious adverse events in patients with rheumatoid arthritis (RA) receiving new therapies, which would help improve drug safety monitoring.

It proposes establishing product-specific registries to follow patients over time, allowing for better comparisons of adverse event incidences between those treated with new drugs and a larger cohort of RA patients on various treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A proposal for developing a large patient population cohort for longterm safety monitoring in rheumatoid arthritis. OMERACT Drug Safety Working Party. Lipani, JA., Strand, V., Johnson, K., et al.[2007]

The HLH-2004 study expanded the diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH) to include three additional markers, improving the accuracy of diagnosis by requiring five out of eight criteria to be met.

The treatment protocol for HLH-2004 includes a combination of chemotherapy and immunotherapy, with specific recommendations for hematopoietic stem cell transplantation in severe cases, highlighting a comprehensive approach to managing this serious condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Henter, JI., Horne, A., Aricó, M., et al.[2022]

The implementation of an evidence-based guideline (EBG) for managing hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) significantly reduced mortality from 50% to 6% in children, indicating improved safety and efficacy of treatment protocols.

Post-EBG, there was a notable improvement in clinical outcomes, including faster diagnosis and treatment initiation, as well as quicker reduction in inflammation markers, suggesting that a multidisciplinary approach enhanced patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Evidence-Based Guideline Improves Outcomes for Patients With Hemophagocytic Lymphohistiocytosis and Macrophage Activation Syndrome. Taylor, ML., Hoyt, KJ., Han, J., et al.[2023]

In a study of 94 children, serum levels of soluble CD163 were found to be significantly elevated in those with hemophagocytic lymphohistiocytosis (HLH), indicating its potential as a diagnostic marker for this condition, especially in EBV-positive patients.

The study suggests that higher levels of soluble CD163 (>10,000 ng/mL) correlate with disease severity in HLH, and monitoring these levels can help evaluate prognosis and treatment response, as seen in follow-up cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Expression of CD163 in children with Epstein-Barr virus infection]. Chen, YL., Chen, FX., Deng, CB., et al.[2015]

Two cases of hemophagocytic lymphohistiocytosis (HLH) progressed to acute leukemia, highlighting a rare but significant connection between HLH and malignancy.

Patients with genetic mutations related to HLH or impaired natural killer (NK) cell function should be closely monitored for potential future cancers, even after HLH symptoms have resolved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemophagocytic lymphohistiocytosis with MUNC13-4 gene mutation or reduced natural killer cell function prior to onset of childhood leukemia. Chang, TY., Jaffray, J., Woda, B., et al.[2021]

Citations

1. electra-therapeutics.com electra-therapeutics.com/electra-therapeutics-to-present-clinical-results-for-ela026-in-secondary-hemophagocytic-lymphohistiocytosisshlh-in-an-oral-session-at-ash-2024/

news Data from completed Phase 1b study of ELA026 highlights results in patients with the poorest prognosis, those with malignancy-associated HLH.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05416307

NCT05416307 | Open-label Study of ELA026 in ... Hemophagocytic lymphohistiocytosis is a rare, aggressive and life-threatening syndrome of excessive immune activation. Secondary hemophagocytic ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/805/530633/ELA026-a-Monoclonal-Antibody-Targeting-Signal

ELA026, a Monoclonal Antibody Targeting Signal Regulatory ... ELA026, a Monoclonal Antibody Targeting Signal Regulatory Protein-α/β1/γ, Rapidly Controls Inflammation and Improves 2-Month Survival in ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10429042/

A PHASE 1B STUDY OF ELA026 IN PATIENTS WITH ... This Phase 1b, open-label, single-arm, multicenter study is investigating the safety, efficacy, PK, and PD of ELA026 following multiple intravenous (IV) doses.

5. electra-therapeutics.com electra-therapeutics.com/electra-therapeutics-presents-positive-clinical-results-from-completed-phase-1b-study-of-ela026-in-secondary-hemophagocytic-lymphohistiocytosis-shlh-in-an-oral-session-at-ash-2024/

news ELA026 demonstrated 100% overall response rate, improved survival, and a favorable safety profile in malignancy-associated HLH (mHLH), the most common type of ...

6. electra-therapeutics.com electra-therapeutics.com/electra-therapeutics-announces-first-patients-dosed-in-the-surpass-phase-2-3-pivotal-study-of-ela026-in-secondary-hemophagocytic-lymphohistiocytosis-shlh/

news “We are highly encouraged by the compelling clinical efficacy and safety that ELA026 has demonstrated to date as a novel mechanism for treating ...