Hemophagocytic LymphohistiocytosesPhase 2/3NCT03985423
A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Emapalumab in Adult Patients With HLH
A Phase 2/3 study testing Emapalumab-Lzsg in people with Hemophagocytic Lymphohistiocytoses, run by Swedish Orphan Biovitrum at 1 site in United States.
Trial summary
Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening condition characterized by uncontrolled hyperinflammation which may develop on the background of several clinical conditions (e.g. autoimmune disease, infection, malignancy). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hemophagocytic Lymphohistiocytoses
- What is being tested?
- Emapalumab-Lzsg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jun 2020to 29 Jun 2021
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients of age 18 and older at the time of HLH diagnosis
- Fulfilment of 5 of the 8 HLH-2004 clinical criteria
- Patients diagnosed with malignancy-associated HLH must be treatment naïve; patients diagnosed with HLH driven by any other etiology or idiopathic can be either treatment naïve or treatment experienced
- Patients with non-malignancy-associated or idiopathic HLH who have already received conventional therapy for HLH must have failed prior treatment as per the treating physician's judgement
- Informed consent signed by the patient or by the patient's legally authorized representative(s) (as required by local law)
- Willing to use highly effective methods of contraception from study drug initiation to 6 months after the last dose of study drug, if female and of childbearing potential.
Who cannot join
- Primary HLH
- Current or scheduled administration of therapies known to trigger the cytokine release syndrome (e.g. chimeric antigen receptor (CAR)-modified T cells, bispecific T cell-engaging antibodies)
- Current or scheduled administration of PD-1/PD-L1/CTLA-4 inhibitors
- Life-expectancy associated with the underlying disease (triggering HLH) < 3 months
- Ongoing participation in an investigational trial, or administration of any investigational treatment within 30 days
- History of hypersensitivity or allergy to any components of emapalumab
Show all 10Show fewer
- Active mycobacteria, Histoplasma capsulatum, or Leishmania infections
- Evidence of latent tuberculosis
- Receipt of a bacille Calmette-Guerin (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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2/3, Open-label, Single Arm, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Emapalumab in Adult Patients With Hemophagocytic Lymphohistiocytosis
Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening condition characterized by uncontrolled hyperinflammation which may develop on the background of several clinical conditions (e.g. autoimmune disease, infection, malignancy). Emapalumab (previously referred to as NI-0501) is a monoclonal antibody neutralizing interferon-gamma (IFN-gamma), a key cytokine driving the inflammation and tissue damage seen in HLH. The purpose of this study is to assess the efficacy, safety and pharmacokinetics of emapalumab in adult patients with secondary HLH.
Read the detailed description
Study NI-0501-10 is an open-label, single arm, multicenter, Phase 2/3 interventional study.
The study enrolls adult patients with hemophagocytic lymphohistiocytosis (HLH), specifically newly diagnosed patients with malignancy-associated HLH (M-HLH), and newly diagnosed or previously treated patients with non-malignancy-associated HLH.
- Conditions
- Hemophagocytic Lymphohistiocytoses
- Being tested
- Emapalumab-Lzsg
- Keywords
- interferon gamma, emapalumab, adult HLH, malignancy-associated HLH, CXCL9
- Medical subject headings
- Lymphohistiocytosis, Hemophagocytic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Emapalumab-LzsgDrug
Also called NI-0501
Patients were administered Emapalumab-Lzsg by intravenous (i.v.) infusion over a period of 1 to 2 hours, at an initial dose of 6 mg/kg and continued at 3 mg/kg, every 3 days for the first 2 weeks (Study Day [SD] 15), and then twice-a-week. If the treating physician deemed appropriate, the dose of emapalumab could be increased (up to 10 mg/kg), guided by clinical and laboratory response.
| Study group | Role | What they receive |
|---|---|---|
| Emapalumab | Experimental | Patients were administered Emapalumab-Lzsg by intravenous (i.v.) infusion over a period of 1 to 2 hours, at an initial dose of 6 mg/kg and continued at 3 mg/kg, every 3 days for the first 2 weeks (Study Day [SD] 15), and then twice-a-week. If the treating physician deemed appropriate, the dose of emapalumab could be increased (up to 10 mg/kg), guided by clinical and laboratory response. Receives: Drug: Emapalumab-Lzsg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response
Achievement of either a Complete or Partial Response
Complete Response is adjudicated if the following are observed:
- No fever = body temperature <37.5°C
- Normal spleen size
- No cytopenia = Absolute Neutrophil Counts >=1.0x10^9/L and platelet count >=100x10^9/L [absence of G-CSF and transfusion support must be documented for at least 4 days to report no cytopenia]
- No hyperferritinemia = serum level is <2000 µg/L
- No evidence of coagulopathy, i.e., normal D-Dimer and/or normal (>150 mg/dL) fibrinogen levels
- No neurological and CSF abnormalities attributed to HLH
- No sustained worsening of sCD25 (as indicated by at least two consecutive measurements that are >2-fold higher than baseline)
Partial Response is adjudicated if there is an improvement (>50% change from baseline or normalization) of at least 3 HLH clinical and laboratory criteria (including Central Nervous System abnormalities).
Measured: Week 4
Secondary outcomes (10)
Best Response on Treatment
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Measured: Week 4; End of Treatment Visit (on average of 12 weeks)
Overall Response
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Measured: End of Treatment Visit (on average of 12 weeks)
Overall Survival
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Measured: End of Treatment Visit (on average of 12 weeks)
Time to Complete Response or Partial Response
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Measured: Week 4; End of Treatment visit (on average of 12 weeks)
Duration of Response
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Measured: Up to 1 year after last emapalumab administration
Hemophagocytic Lymphohistiocytosis Relapse
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Measured: Up to 1 year after last emapalumab administration
Incidence, Severity, Causality and Outcomes of Serious Adverse Events and Non-serious Adverse Events
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Measured: Up to 1 year after last emapalumab administration
Serum Concentrations of Emapalumab
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Measured: Up to 1 year after last emapalumab administration
Serum Biomarker Levels
Levels of interferon-gamma, C-X-C chemokine ligand 9, soluble CD25, interleukin-6.
Measured: Up to 1 year after last emapalumab administration
Incidence of Anti-Drug Antibodies Against Emapalumab
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
Measured: Up to 1 year after last emapalumab administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2019
- Study start2 Jun 2020
- Primary completion29 Jun 2021
- Study completion29 Jun 2021
Why it stopped: Sponsor Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hemophagocytic LymphohistiocytosesStudies of the same condition, open and under way.
- More trials run by Swedish Orphan BiovitrumThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swedish Orphan Biovitrum
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Light Chain Bioscience - Novimmune SA
- Responsible party
- Sponsor
- Investigators
- Radmila Kanceva, Study director, Swedish Orphan Biovitrum
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03985423
- Sponsor's protocol ID
- NI-0501-10
- Status last verified
- Sep 2023
- First submitted
- 23 May 2019
- Last updated
- 6 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2/3, Open-label, Single Arm, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Emapalumab in Adult Patients With Hemophagocytic Lymphohistiocytosis
- ClinicalTrials.gov ID
- NCT03985423
- Acronym / sponsor ID
- NI-0501-10
- Conditions
- Hemophagocytic Lymphohistiocytoses
- Keywords
- interferon gamma, emapalumab, adult HLH, malignancy-associated HLH, CXCL9
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor Decision
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Swedish Orphan BiovitrumIndustry (pharma, biotech, devices)
- Collaborators
- Light Chain Bioscience - Novimmune SA
- Study start
- 2 Jun 2020 (actual)
- Primary completion
- 29 Jun 2021 (actual)
- Study completion
- 29 Jun 2021 (actual)
- First posted
- 13 Jun 2019 (actual)
- Results
- Posted 6 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening condition characterized by uncontrolled hyperinflammation which may develop on the background of several clinical conditions (e.g. autoimmune disease, infection, malignancy). Emapalumab (previously referred to as NI-0501) is a monoclonal antibody neutralizing interferon-gamma (IFN-gamma), a key cytokine driving the inflammation and tissue damage seen in HLH. The purpose of this study is to assess the efficacy, safety and pharmacokinetics of emapalumab in adult patients with secondary HLH.
Detailed description
Study NI-0501-10 is an open-label, single arm, multicenter, Phase 2/3 interventional study.
The study enrolls adult patients with hemophagocytic lymphohistiocytosis (HLH), specifically newly diagnosed patients with malignancy-associated HLH (M-HLH), and newly diagnosed or previously treated patients with non-malignancy-associated HLH.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Emapalumab | Experimental | Drug: Emapalumab-LzsgPatients were administered Emapalumab-Lzsg by intravenous (i.v.) infusion over a period of 1 to 2 hours, at an initial dose of 6 mg/kg and continued at 3 mg/kg, every 3 days for the first 2 weeks (Study Day [SD] 15), and then twice-a-week. If the treating physician deemed appropriate, the dose of emapalumab could be increased (up to 10 mg/kg), guided by clinical and laboratory response. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male and female patients of age 18 and older at the time of HLH diagnosis
- Fulfilment of 5 of the 8 HLH-2004 clinical criteria
- Patients diagnosed with malignancy-associated HLH must be treatment naïve; patients diagnosed with HLH driven by any other etiology or idiopathic can be either treatment naïve or treatment experienced
- Patients with non-malignancy-associated or idiopathic HLH who have already received conventional therapy for HLH must have failed prior treatment as per the treating physician's judgement
- Informed consent signed by the patient or by the patient's legally authorized representative(s) (as required by local law)
Key exclusion criteria (10 listed)
- Primary HLH
- Current or scheduled administration of therapies known to trigger the cytokine release syndrome (e.g. chimeric antigen receptor (CAR)-modified T cells, bispecific T cell-engaging antibodies)
- Current or scheduled administration of PD-1/PD-L1/CTLA-4 inhibitors
- Life-expectancy associated with the underlying disease (triggering HLH) < 3 months
- Ongoing participation in an investigational trial, or administration of any investigational treatment within 30 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Emapalumab-LzsgAlso: NI-0501Patients were administered Emapalumab-Lzsg by intravenous (i.v.) infusion over a period of 1 to 2 hours, at an initial dose of 6 mg/kg and continued at 3 mg/kg, every 3 days for the first 2 weeks (Study Day [SD] 15), and then twice-a-week. If the treating physician deemed appropriate, the dose of emapalumab could be increased (up to 10 mg/kg), guided by clinical and laboratory response. | Drug | Emapalumab |
Primary outcome
Overall Response
Time frame: Week 4
Achievement of either a Complete or Partial Response Complete Response is adjudicated if the following are observed: * No fever = body temperature <37.5°C * Normal spleen size * No cytopenia = Absolute Neutrophil Counts >=1.0x10^9/L and platelet count >=100x10^9/L [absence of G-CSF and transfusion support must be documented for at least 4 days to report no cytopenia] * No hyperferritinemia = serum level is <2000 µg/L * No evidence of coagulopathy, i.e., normal D-Dimer and/or normal (>150 mg/dL) fibrinogen levels * No neurological and CSF abnormalities attributed to HLH * No sustained worsening of sCD25 (as indicated by at least two consecutive measurements that are >2-fold higher than baseline) Partial Response is adjudicated if there is an improvement (>50% change from baseline or normalization) of at least 3 HLH clinical and laboratory criteria (including Central Nervous System abnormalities).
10 secondary outcomes
Best Response on Treatment
Time frame: Week 4; End of Treatment Visit (on average of 12 weeks)
Overall Response
Time frame: End of Treatment Visit (on average of 12 weeks)
Overall Survival
Time frame: End of Treatment Visit (on average of 12 weeks)
Time to Complete Response or Partial Response
Time frame: Week 4; End of Treatment visit (on average of 12 weeks)
Duration of Response
Time frame: Up to 1 year after last emapalumab administration
Hemophagocytic Lymphohistiocytosis Relapse
Time frame: Up to 1 year after last emapalumab administration
Incidence, Severity, Causality and Outcomes of Serious Adverse Events and Non-serious Adverse Events
Time frame: Up to 1 year after last emapalumab administration
Serum Concentrations of Emapalumab
Time frame: Up to 1 year after last emapalumab administration
Serum Biomarker Levels
Time frame: Up to 1 year after last emapalumab administration
Incidence of Anti-Drug Antibodies Against Emapalumab
Time frame: Up to 1 year after last emapalumab administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Radmila Kanceva study director
Swedish Orphan Biovitrum
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Emapalumab-Lzsg in people with Hemophagocytic Lymphohistiocytoses, run by Swedish Orphan Biovitrum at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response (time frame: Week 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2023.