An Open-label, Single-arm, Multicenter Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Multiple Doses of ELA026 in Participants with Secondary Hemophagocytic Lymphohistiocytosis (sHLH).

• Conditions: Secondary Hemophagocytic Lymphohistiocytosis (sHLH); 10021460

• Registration Number: NL-OMON55948
• Lead Sponsor: Electra Therapeutics Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 8

Inclusion Criteria

Age
1. >=12 years at the time of sHLH diagnosis (Cohort 1)
2. >=6 years at the time of sHLH diagnosis (Cohorts 2-4)

Type of Participant and Disease Characteristics (Cohort 1-2)
1. Treatment naïve (participants >=12 years of age only), OR
2. Relapsed or refractory sHLH defined as:
a. Participant has failed to respond to 2 weeks of treatment with
tociluzumab, anakinra, or other HLH therapy with a less than 50%
decrease in serum ferritin, OR
b. Participant has received 4 doses of etoposide with a less than 50%
decrease in serum ferritin 72 hours after last dose, OR
c. On a case-by-case basis as determined by the Medical Monitor

Type of Participant and Disease Characteristics (Cohort 2 as of
amendment 4, Cohort 3-4)
1. Treatment naïve, OR
2. Early refractory sHLH defined as:
a. The participant receiving approximately <1 week of any HLH-directed
therapy with insufficient clinical or laboratory response judged by
investigator at screening, OR
b. On a case-by-case basis as determined by the Medical Monitor

3. Participants must meet one of the following:
a. Participant has an sHLH confirmed diagnosis (inclusive of MAS)
based on fulfilling at least 5 of the 8 modified HLH-2004 criteria below.
These criteria may have been assessed prior to the screening period.
Participants not fulfilling at least 5 of the 8 modified HLH-2004 criteria
may be considered on a case-by-case basis if the diagnosis of sHLH is
clinically established especially if one of the criterion is a specialized test
result that is performed by a reference laboratory and is not yet
available.

Clinical Criteria
1. Fever
2. Splenomegaly
Laboratory Criteria
1. Cytopenia (affecting >=2 of 3 lineages in the peripheral blood):
Hemoglobin (<90 g/L), Platelet (<100 x 10*9/L), Neutrophil (<1.0 x
10*9/L)
2. Hypertriglyceridemia and/or hypofibrinogenemia:
Fasting triglycerides >=265 mg/dL or >=3.0 mmol/L, fibrinogen <=1.5 g/L
Histopathologic Criteria
1. Hemophagocytosis in bone marrow or spleen or lymph nodes or liver
2. Low or absent NK-cell activity (according to laboratory reference)
3. Ferritin >=500 microgram/L (or ng/mL)
4. Elevated sCD25 (e.g., soluble CD25, also known as soluble IL-2
receptor)
OR
b. Participants may be diagnosed with malignancy-associated HLH
(mHLH) by meeting the optimized HLH inflammatory (OHI) Index of
sCD25 >3900 U/mL (or 23,400 in pg/mL) and ferritin >1000 ng /mL
(Zoref-Lorenz et al, 2022).

Sex and Contraception
1. Male or female
Contraception use by men or women should be consistent with local
regulations regarding the methods of contraception for those
participating in clinical studies.
2. Female participants must be either of non-reproductive potential (ie.,
premenarchal or post menopausal by history with no menses for >=1
year; or have a history of hysterectomy, bilateral tubal ligation or
bilateral oophorectomy) or, if of childbearing potential, must have a
negative pregnancy test in serum prior to trial entry and must be willing
to practice at least one of the following highly effective methods of birth
control (<1% failure rate per year) at least from 28 days prior to study
drug initiation to 30 days after the last dose of study drug:
a. True abstinence, when this is in line with the preferred and usual
lifestyle of the participant, from sexual int

Exclusion Criteria

Medical Conditions
1. Known or previous treatment for primary HLH.
2. Any other significant concurrent, uncontrolled medical condition that
in the opinion of the Investigator contraindicates participation in this
study.
3. Unknown trigger for sHLH
4. Active, relapsed/refractory malignancy for which no suitable
therapies are available to treat the malignancy triggering the HLH
Prior/Concurrent Therapy
1. Allogeneic hemopoietic stem cell transplant (HSCT) within 100 days
of the first dose of ELA026.
2. Ongoing administration of any therapies used primarily to treat HLH
excluding dexamethasone.
3. Live or attenuated vaccine received within 6 weeks or bacille
Calmette-Guerin (BCG) vaccine within 12 weeks prior to Screening.
Other
1. History of hypersensitivity or allergy to dexamethasone.
2. History of hypersensitivity or allergy to any components of ELA026.
3. Currently breastfeeding.
4. Unwilling or unable to comply with trial.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Objective:<br /><br>To determine the safety of ELA026 administered IV and SC to participants with<br /><br>sHLH.<br /><br>End point:<br /><br>Incidence of adverse events (AEs) including dose-limiting toxicities (DLTs),<br /><br>serious adverse events (SAEs), deaths, AEs leading to withdrawal from study.<br /><br><br /><br>Primary Objective:<br /><br>To identify the RP3D (Recommended Phase 3 Dose) and schedule for ELA026.<br /><br>End point:<br /><br>Safety, efficacy, PD (overall assessment).</p><br>