Open-label Phase 1b study to evaluate safety and efficacy of ELA026 in Adults and Adolescents participants with sHLH.

Phase 1

Conditions: sHLH is a rare and life-threatening inflammatory syndrome characterized by dysregulated immune function. The disease is associated with a massive systemic inflammatory response for which patients require immediate and aggressive treatment with intensive care. Clinically, patients present with fever, hepatomegaly, pancytopenia, splenomegaly, hypotension, and coagulopathy. It is difficult to assess the true epidemiology of HLH due to the rarity of the condition.
MedDRA version: 20.0Level: SOCClassification code 10021428Term: Immune system disordersSystem Organ Class: 10021428 - Immune system disorders
MedDRA version: 21.1Level: PTClassification code 10058092Term: Multi-organ disorderSystem Organ Class: 10018065 - General disorders and administration site conditions
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2021-001387-20-ES

Lead Sponsor: Electra Therapeutics, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 24

Inclusion Criteria

Age
1. =12 years at the time of HLH diagnosis.
Type of Participant and Disease Characteristics
1. Treatment naive
OR
2. Relapsed or refractory HLH defined as:
a. Participant has failed to respond to 2 weeks of non-etoposide, non-steroid 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
3. Participant is hospitalized with an HLH confirmed diagnosis based on fulfilling 5 out of 8 HLH-2004 criteria below (Henter, Horne, et al., 2007):
Clinical Criteria
1. Fever =38.5C
2. Splenomegaly
Laboratory Criteria
1. Cytopenia (affecting =2 of 3 lineages in the peripheral blood):
Haemoglobin (<90 g/L), Platelet (<100 x 10*9/L), Neutrophil (<1.0 x 10*9/L).
2. Hypertriglyceridemia and/or hypofibrinogenemia:
Fasting triglycerides =1.0 mmol/L or =3SD of the normal value for age, fibrinogen =1.5 g/L or 3SD.
Histopathologic Criteria
1. Hemophagocytosis in bone marrow or spleen or lymph nodes or liver.
2. Low or absent natural killer (NK)-cell activity (according to local laboratory reference).
3. Ferritin =500 microgram/L
4. Elevated soluble CD25 (e.g., soluble IL-2 receptor).
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., 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.
3. Male must be willing to use a condom during penile-vaginal intercourse with female partners of child-bearing potential, throughout the study and up to 60 days after the last dose.
Informed Consent
1. Participant or legally authorized representative(s) (LAR) capable of giving signed informed consent.
2. Minor participants must be capable of giving written assent as appropriate per the applicable age.
Are the trial subjects under 18? yes
Number of subjects for this age range: 5
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 19
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.
Prior/Concurrent Therapy
1. Hemapoietic Stem Cell Transplant (HSCT) within 100 days of the first dose of ELA026.
2. Treatment with CAR T-Cell therapy within 3 months of the first dose of ELA026.
3. Ongoing administration of any investigational treatment or treatment for HLH (excluding dexamethasone) within 14 days prior to Screening or 5 drug half-lives, whichever is shorter.
4. Live or attenuated vaccine received within 6 weeks or bacille Calmette-Guerin (BCG) vaccine within 12 weeks prior to Screening.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: • To determine the safety of ELA026 administered IV and SC to adolescent and adult participants with sHLH.<br><br>• To identify the RP3D and schedule for ELA026.;Secondary Objective: • To characterize the pharmacokinetic (PK) profile of ELA026 administered IV and SC to adolescent and adult participants with sHLH.<br><br>• To determine the efficacy of ELA026 administered IV and SC to adolescent and adult participants with sHLH.<br><br>• To characterize the pharmacodynamic (PD) effect of ELA026 administered IV and SC to adolescent and adult participants with sHLH.<br><br>• To assess the immunogenicity of ELA026 administered IV and SC to adolescent and adult participants with sHLH.;Primary end point(s): • Incidence of adverse events (AEs) including dose-limiting toxicities (DLTs), serious adverse events (SAEs), deaths, AEs leading to withdrawal from study.<br><br>• Safety, efficacy, PD.;Timepoint(s) of evaluation of this end point: Evaluated on an ongoing basis.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • 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.<br><br>• Plasma concentrations and PK parameters of ELA026.<br><br>• Change from baseline in monocytes and T lymphocytes.<br><br>• Incidence of Anti-drug antibodies (ADAs) to ELA026.;Timepoint(s) of evaluation of this end point: After the given period is completed.

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