Study to Assess the Efficacy and Safety of Emapalumab in Primary Haemophagocytic Lymphohistiocytosis

• Sponsor: Swedish Orphan Biovitrum (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03312751
• Collaborator: (none)
• Enrollment: 34
• Locations: 28
• Arm: 1
• Anticipated Duration (Months): 43.8
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to expand the knowledge on the efficacy and safety of emapalumab (previously known as NI-0501) as a treatment for primary haemophagocytic lymphohistiocytosis (HLH) patients, with special focus on long-term outcome and quality of life assessments. Emapalumab can be administered as the first-line therapy, to patients not previously treated with the current standard of care, or can be given to patients who have either failed or were unable to tolerate the available standard of care.

Emapalumab is to be administered until the start of conditioning, with an anticipated duration ranging from a minimum of 4 weeks to approximately 12 weeks and not exceeding 6 months.

After treatment completion, patients will continue in the study for long-term follow-up until 1 year after either HSCT or last emapalumab infusion (if HSCT is not performed).

Condition or Disease	Intervention/Treatment	Phase
Primary Hemophagocytic Lymphohistiocytosis	Drug: Emapalumab	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Single Arm, Multicenter Study to Broaden Access to Emapalumab, an Anti-Interferon Gamma (Anti-IFNγ) Monoclonal Antibody, and to Assess Its Efficacy, Safety, Impact on Quality of Life, and Long-term Outcome in Pediatric Patients With Primary Hemophagocytic Lymphohistiocytosis
• Actual Study Start Date: Feb 5, 2019
• Anticipated Primary Completion Date: Oct 1, 2022
• Anticipated Study Completion Date: Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Emapalumab	Drug: Emapalumab; Emapalumab will be administered by intravenous infusion, twice weekly.

Outcome Measures

Primary Outcome Measures

1. Overall Response at Week 8 or End of Treatment (if earlier) [Up to Week 8]

   Achievement of either Complete or Partial Response or HLH Improvement, at Week 8 or EOT (whichever occurs earlier)

Secondary Outcome Measures

1. Overall Survival [Up to 18 months]

   Including survival to HSCT and post-HSCT

2. Number of patients proceeding to HSCT [Up to 18 months]

   Number of patients proceeding to HSCT

3. Change in PedsQL Score [Up to 18 months]

   Assessment of the quality of life using the PedsQL "Pediatric Quality of Life Inventory"

4. Incidence, severity, causality and outcomes of AEs (serious and non-serious) [Up to 18 months]

   Incidence of adverse events

5. Immunogenicity [Up to 18 months]

   Incidence of circulating antibodies against emapalumab

Other Outcome Measures

1. Overall Response at start of conditioning [Up to 6 months]

   Achievement of either Complete or Partial Response or HLH Improvement, at start of conditioning

2. Serum concentrations of emapalumab [Up to 18 months]

   Serum concentrations of emapalumab

3. Pharmacodynamic parameters [Up to 18 months]

   Levels of total IFNγ, markers of its neutralization (CXCL9 and CXCL10) and other relevant disease biomarkers e.g. sCD25

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Primary HLH patients with active disease.

• Treatment naïve patients or patients having already received HLH conventional therapy, but having failed or unable to tolerate current standard of care.

• Informed consent signed by the patient or by the patient's legally authorized representative.

• Guidance on contraception

Exclusion Criteria:

• Diagnosis of secondary HLH consequent to a proven rheumatic, metabolic or neoplastic disease.

• Active Mycobacteria, Histoplasma Capsulatum, Shigella, Salmonella, Campylobacter or Leishmania infections.

• Evidence of latent tuberculosis.

• Presence of malignancy.

• Concomitant disease or malformation severely affecting cardiovascular, pulmonary, central nervous system (CNS), liver, or renal function, that in the opinion of the Investigator may significantly affect the likelihood to respond to treatment and/or the assessment of emapalumab safety and/or efficacy

• History of hypersensitivity or allergy to any component of the study regimen

• Receipt of a BCG vaccine within 12 weeks prior to Screening

• Receipt of a live or attenuated live (other than BCG) vaccine within 6 weeks prior to Screening

• Pregnant or lactating female patients.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children Hospital	Phoenix	Arizona	United States	85016
2	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
3	Children's Hospital Colorado	Aurora	Colorado	United States	80045-7106
4	Alfred I. duPont Hospital for Children - Nemours Center for Cancer and Blood Disorders - Division of Pediatric Hematology Oncology	Wilmington	Delaware	United States	19803
5	Children's Healthcare of Atlanta	Atlanta	Georgia	United States	30329
6	Dana-Farber Cancer Institute (DFCI)	Boston	Massachusetts	United States	02215
7	Spectrum Health Helen Devos Children's Hospital	Grand Rapids	Michigan	United States	49503
8	Cincinnati Children's Hospital	Cincinnati	Ohio	United States	45229
9	Texas Children's Cancer Center	Houston	Texas	United States	77030
10	Seattle Children's Hospital	Seattle	Washington	United States	98109
11	Hopital Ste-Justine Research Center	Montréal		Canada	QC H3T 1C5
12	Hospital for Sick Children	Toronto		Canada	ON M5G 1X8
13	Children's and Women's Health Centre of British Columbia	Vancouver		Canada	V6H 3V4
14	Universitätsklinikum Essen	Essen		Germany	45122
15	Medical Center- University of Freiburg	Freiburg		Germany	79106
16	Universitätsklinikum Eppendorf	Hamburg		Germany	20246
17	Istituto Giannina Gaslini	Genova		Italy	16147
18	Fondazione MBBM, Ospedale San Gerardo	Monza		Italy	20900
19	Ospedale Pediatrico Bambino Gesu	Rome		Italy	00165
20	Ospedale della Donna e del Bambino	Verona		Italy	37126
21	Hospital Universitario Vall d'Hebron	Barcelona		Spain	08035
22	Hospital Universitario Niño Jesús	Madrid		Spain	28009
23	Karolinska University Hospital Huddinge	Stockholm		Sweden	14186
24	University Children's Hospital Zurich - Eleonorenstiftung	Zürich		Switzerland	CH-8032
25	University Children's Hospital Zurich	Zürich		Switzerland	CH-8032
26	Leeds Children Hospital	Leeds		United Kingdom	LS13EX
27	Great Ormond Street Hospital	London		United Kingdom	WC1N 3JH
28	Royal Manchester Children's Hospital	Manchester		United Kingdom	M13 9WL

Sponsors and Collaborators

• Swedish Orphan Biovitrum

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Swedish Orphan Biovitrum
• ClinicalTrials.gov Identifier: NCT03312751
• Other Study ID Numbers: NI-0501-09
• First Posted: Oct 18, 2017
• Last Update Posted: Nov 5, 2021
• Last Verified: Nov 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Swedish Orphan Biovitrum: Interferon-gamma; NI-0501; primary HLH; emapalumab
• Additional relevant MeSH terms: Lymphohistiocytosis, Hemophagocytic

Study Results

No Results Posted as of Nov 5, 2021