Primary Hemophagocytic Lymphohistiocytosis
Conditions
Keywords
pHLH
Brief summary
The goal of this post-authorization study is to describe safety and efficacy of emapalumab in treatment experienced Chinese patients with pHLH.
Detailed description
This is an open-label, multi center, single arm, post-authorization study aiming to describe safety and efficacy of emapalumab in treatment experienced Chinese patients with confirmed or suspected primary hemophagocytic lymphohistiocytosis (pHLH). The main objectives of the study are to collect safety and efficacy data on emapalumab in treatment experienced Chinese pHLH patients
Interventions
DRUGEmapalumab-Lzsg 5 MG/ML [Gamifant]
iv
Sponsors
Swedish Orphan Biovitrum
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is an open-label, single-arm, multi-centre study to collect safety and efficacy data on emapalumab in treatment experienced male and female patients diagnosed with pHLH. The study will be performed in China.
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Male and female HLH patients of any age. 2. Patients diagnosed with confirmed or suspected pHLH, based on; a molecular diagnosis or familial history consistent with pHLH or fulfilment of HLH-2004 diagnostic criteria, i.e., five out of eight of the criteria below: * Fever * Splenomegaly * Cytopenias affecting 2 of 3 lineages in the peripheral blood (hemoglobin \<90 g/L; platelets \<100 x 109/L; neutrophils \<1 x 109/L) * Hypertriglyceridemia (fasting triglycerides ≥3 mmol/L or ≥265 mg/dL) and/or hypofibrinogenemia (≤1.5 g/L) * Hemophagocytosis in bone marrow, spleen, or lymph nodes, with no evidence of malignancy. * Low or absent NK-cell activity * Ferritin ≥500 μg/L * Soluble CD25 (sCD25; i.e., soluble IL-2 receptor) ≥2400 U/mL 3. Presence of active HLH disease as assessed by the investigator. 4. Patients must fulfil one of the following criteria as assessed by the investigator: * Having not responded to previous conventional treatment of HLH * Having not achieved a satisfactory response to previous conventional treatment of HLH or worsened * Having reactivated HLH * Showing intolerance to previous conventional treatment of HLH At the time of enrollment, eligible patients might still be receiving treatment (induction or maintenance) or might have already discontinued it. 5. Expectation of survival beyond 1 week as judged by the investigator. 6. Patient has expectation of proceeding to HSCT 7. Informed consent signed by the patient (as required by local law), or by the patient's legally authorized representative(s) with the assent of patients who are legally capable of providing it, as applicable. 8. 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.
Exclusion criteria
1. Diagnosis of secondary HLH consequent to a proven rheumatic, metabolic or neoplastic disease. 2. Active mycobacteria, Histoplasma capsulatum, Salmonella, or Leishmania infections. 3. Evidence of latent tuberculosis. 4. Presence of malignancy. 5. Existence of any severe co-morbidity or any other medical condition which, in the opinion of the investigator, makes the patient unsuitable for the treatment 6. History of hypersensitivity or allergy to any component of the study regimen (e.g., polysorbate). 7. Receipt of a Bacillus Calmette-Guérin (BCG) vaccine within 12 weeks prior to Screening. 8. Receipt of a live or attenuated live (other than BCG) vaccine within 4 weeks prior to Screening. 9. Pregnant or lactating female patients. 10. Enrollment in another concurrent clinical interventional study, or intake of an IMP, within three months prior to inclusion in this study 11. Any condition or circumstance that in the opinion of the Investigator may make the patient unlikely to complete the study or comply with study procedures or requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Permanent Discontinuation of Study Drug Due to Emapalumab-related Adverse Event | Until conditioning for hematopoietic stem cell transplant (HSCT), likely within 6 months from first dose | Number of participants permanently discontinuation of study drug due to emapalumab-related adverse event as judged by Investigator, until conditioning for hematopoietic stem cell transplant (HSCT), likely within 6 months from first dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response | End of treatment or week 8 (whichever occurs earlier) | Number of participants with an overall response i.e., achievement of either Complete Response or Partial Response or HLH Improvement, at end of treatment or week 8 (whichever occurs earlier). |
| Time to First Overall Response | End of treatment, likely within 6 months from first dose | Time to first overall response from first dose of study drug to the first achievement of response (Complete Response, Partial Response, or HLH Improvement) |
| Cumulative Duration of Response | End of treatment, likely within 6 months from first dose | Cumulative duration of response is defined as total time in response from the first achievement of an Overall Response until EOT. For patients who achieve a response, lost that response, and then achieve it subsequently, the total time in response is calculated by adding together these separate periods in response. |
| Ability to Reduce Glucocorticoids by 50% or More | End of treatment, likely within 6 months from first dose | Number of participants able to reduce glucocorticoids by 50% or more of the baseline dose at any time point of the treatment period |
| Investigator Assessed Response | End of treatment | Investigator's assessment of how patient responds to treatment and rated as complete response, partial response, or no response |
| Survival | End of study (1 year) | Number of participants surviving to start of HSCT conditioning and Number of participants that underwent HSCT surviving after HSCT to end of study |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORRui Zhang, MD, Prof
Beijing Children's Hospital
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 7 years |
| Child-bearing potential No | 4 Participants |
| Child-bearing potential Yes | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 13 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 13 |
| other Total, other adverse events | 13 / 13 |
| serious Total, serious adverse events | 7 / 13 |
Outcome results
None listed