Secondary Hemophagocytic Lymphohistiocytosis (sHLH)
Conditions
Interventions
Intervention Name: ELA026
Type: Biologic
Dose Formulation: Solution for IV infusion or SC injection.
Unit Dose Strength(s): Each vial contains 150 mg of ELA026 (50 mg/mL) solution
for IV infusion/
Sponsors
Electra Therapeutics Inc.
Eligibility
Age
2 Years to 99 Years
Inclusion criteria
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 =2 of 3 lineages in the peripheral blood): Hemoglobin (=265 mg/dL or >=3.0 mmol/L, fibrinogen =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
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Objective: To determine the safety of ELA026 administered IV and SC to participants with sHLH. End point: Incidence of adverse events (AEs) including dose-limiting toxicities (DLTs), serious adverse events (SAEs), deaths, AEs leading to withdrawal from study. Primary Objective: To identify the RP3D (Recommended Phase 3 Dose) and schedule for ELA026. End point: Safety, efficacy, PD (overall assessment). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Objective: To determine the efficacy of ELA026 administered IV and SC to participants with HLH. End points: Best response by Week 4 defined as either complete response (CR) modified complete response (mCR) or partial response (PR) evaluated by objective clinical and laboratory parameters. Secondary Objective: To characterize the pharmacokinetic (PK) profile of ELA026 administered IV and SC to participants with sHLH. End points: Plasma concentrations and PK parameters of ELA026. Secondary Objective: To characterize the pharmacodynamic (PD) effect of ELA026 administered IV and SC to participants with sHLH. End points: Change from baseline in monocytes and CRP. Secondary Objective: To assess the immunogenicity of ELA026 administered IV and SC to participants with sHLH. End points: Incidence of anti-drug antibodies (ADAs) to ELA026. | — |
Countries
Netherlands
Outcome results
None listed