This study has been transitioned to CTIS with ID 2024-516153-52-00 check the CTIS register for the current data. Primary objective: To demonstrate efficacy of emapalumab in the treatment of patients in:• Cohort 1: Macrophage activation syndrome (MAS…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary efficacy endpoint:
• Proportion of patients with complete response (CR) at Week 8 after first
administration of emapalumab.
Secondary outcome
Secondary endpoints:
• GCs tapering to a dose < 50 % of prednisolone (PDN) equivalent at the time of
emapalumab start or to the same (or lower) dose being administered before the
occurrence of MAS (in patients already treated for the underlying condition)
whichever occurs first at any time during the study.
• GCs tapering to <=1mg/kg/day of PDN equivalent at any time during the study.
• Time to achieve GCs tapering (as defined in the 2 bullets above).
• Time to first CR.
• Proportion of patients with OR as defined by CR or partial response (PR).
• Time to first OR as defined by CR or PR.
• MAS recurrence at any time after achievement of CR
• Withdrawal from the study due to lack of response as per Investigator
decision.
• Survival time.
Background summary
MAS will lead to an abnormally high production of interferon gamma (IFNγ), a
protein which is believed to be responsible for too much inflammation within
the body. This inflammation can cause a lot of harm to your tissues and organs
and can be responsible of high temperature (fever), joint pains, bleeding
and increase in the size of some of the body organs such as the liver. The
inflammation may also lead to other serious complications in your organs and
can be life threatening.
To fight against this exaggerated inflammation, an urgent and aggressive
treatment and constant medical supervision is required.
To date, there is no specific medical treatment against MAS approved by any
health authority especially if the disease is not controlled with the high dose
of corticosteroid medication.
Emapalumab may neutralize the effects of this inflammatory protein (IFNγ) and
aims to reduce and/or remove the inflammation in your body, stopping organ
damage and trying to restore a healthier condition.
Study objective
This study has been transitioned to CTIS with ID 2024-516153-52-00 check the CTIS register for the current data.
Primary objective:
To demonstrate efficacy of emapalumab in the treatment of patients in:
• Cohort 1: Macrophage activation syndrome (MAS) in the context of systemic
juvenile idiopathic arthritis (sJIA) and adult onset Still*s disease (AOSD).
• Cohort 2: MAS in the context of pediatric and adult systemic lupus
erythematosus (SLE).
Secondary objectives:
• To demonstrate efficacy of emapalumab with respect to tapering of
glucocorticoids (GCs).
• To evaluate the time to onset of response to emapalumab treatment.
• To evaluate efficacy of emapalumab with respect to overall response (OR).
• To evaluate the sustained efficacy of emapalumab treatment.
• To evaluate the patient*s survival after treatment with emapalumab.
• To evaluate the safety and tolerability of emapalumab.
• To evaluate patient-reported outcome of MAS in patients treated with
emapalumab.
• To determine the pharmacokinetic (PK) profile of emapalumab.
• To determine the pharmacodynamic (PD) profile of emapalumab.
• To determine the immunogenicity of emapalumab.
Exploratory objectives:
• To explore the correlation between PD parameters and relevant laboratory
parameters per cohort.
Study design
Study NI-0501-14 is an open-label 2-cohort, single arm, multicenter,
interventional, phase 2/3 study.
The study enrolls pediatric and adult patients between 6 months and 80 years of
age with different etiologies of MAS. The patients will be assigned to
different cohorts as per their underlying disease:
• Cohort 1: MAS in the context of sJIA and AOSD.
• Cohort 2: MAS in the context of pediatric and adult SLE.
Each cohort in this study is designed as a single arm study and will be
composed of 2 phases: one Run-in phase and one Interventional phase.
The Run-in phase will enroll patients as defined in Cohorts 1 and 2, and
requiring treatment with GCs. These patients will be treated as per
Investigator decision. Patients will be followed for a maximum of 12 weeks, or
until reaching a MAS remission as per Investigator assessment, or until
presenting an inadequate response to GCs as assessed by the Investigator,
whichever occurs first.
Every effort should be taken to enroll patients starting from the Run-in phase
(i.e., before starting treatment with GCs). However, it should be noted that
this phase is not compulsory, therefore patients can join the study directly in
the Interventional phase. Patients who also failed GCs plus other MAS therapies
and meet all the eligibility criteria may be enrolled in the Interventional
phase. If at any time during the Run-in phase, patients present an inadequate
response to GCs and additionally meet all eligibility criteria of the
Interventional phase, they will be invited to continue into the Interventional
phase of the study.
Enrollment in the Run-in phase will be achieved when the last patient of the
Interventional phase is enrolled. At the time of completion of enrollment into
the Interventional phase, patients completing the Run-in phase will not be
denied treatment with emapalumab and enrollment into the Interventional phase
if needed, and upon fulfillment of all eligibility criteria.
A re-treatment with emapalumab is allowed during the Long-term follow-up period
of the study if patients present a recurrence of MAS.
An interim analysis assessing efficacy will be performed after 16 treated
patients in Cohort 1 have reached 8 weeks after first dose of emapalumab, or
earlier if the patients discontinued the study. Enrollment in Cohort 1 may be
closed upon results of this interim analysis. The data from the interim
analysis will be used for regulatory submission purposes.
Intervention
Patients enrolled in the Interventional phase will receive emapalumab.
Emapalumab will be administered by i.v. infusion at an initial dose of 6 mg/kg
over a period of 1 to 2 hours depending on the volume to be infused. Emapalumab
treatment will be continued at the dose of 3 mg/kg
every 3 days until Study Day 16 (SD16), and then twice-a-week for additional 2
weeks, i.e., until SD28
Study burden and risks
Please refer to the ICF for risks and discomforts associated with study
medication and study procedures.
Riehenring 182
Basel 4058
CH
Riehenring 182
Basel 4058
CH
Listed location countries
Age
Inclusion criteria
Inclusion criteria
Run-in phase in all cohorts
1. Informed consent provided by the patient or by the patient's legally
authorized representative(s) with the assent of patients who are legally
capable of providing it, as required by local law.
2. Male and female patients aged between 6 months and 80 years of age at the
time of diagnosis of active MAS.
3. MAS defined as per the criteria defined below for each cohort and requiring
treatment with GCs as per standard of care.
Interventional phase in all cohorts
1. Informed consent provided by the patient or by the patient's legally
authorized representative(s) with the assent of patients who are legally
capable of providing it, as required by local law.
2. Male and female patients aged between 6 months and 80 years of age at the
time of diagnosis of active MAS.
3. Patients who have shown an inadequate response to high dose intravenous
(i.v.) GCs administered for at least 3 days according to local standard
clinical practice, including but not limited to pulses of 30 mg/kg
methylprednisolone (mPDN) on 3 consecutive days. High i.v. GCs dose is
recommended not to be lower than 2 mg/kg/ day PDN equivalent (or at least 60
mg/day in pediatric patients of 30 kg or more and at least 1 g/day in adult MAS
patients). In case of rapid worsening of the patient*s condition and/or
laboratory parameters, as per Investigator judgment, inclusion may occur within
less than 3 days from starting high dose GCs.
4. Diagnosis of active MAS confirmed by the treating rheumatologist, having
ascertained the followings:
a. Febrile patients presenting with ferritin > 684 ng/mL.
b. and any 2 of:
i. Platelet count <= 181 x109/L
ii. Aspartate aminotransferase (AST) -level > 48 U/L
iii. Triglycerides > 156 mg/dL
iv. Fibrinogen level <= 360 mg/dL
5. Female patients of child-bearing potential (sexually or non sexually
active). Female patients who are sexually active must be willing to use highly
effective methods of contraception from study drug initiation to 6 months after
the last dose of study drug.
Specific inclusion criteria for Cohort 1 and Cohort 2
6. Cohort 1:
a. Confirmed sJIA diagnosis. For patients presenting with MAS in the context of
the onset of sJIA, high presumption of sJIA will suffice for eligibility.
b. Confirmed diagnosis of AOSD as per Yamaguchi criteria (Yamaguchi et al.
1992).
7. Cohort 2:
a. Confirmed diagnosis of SLE as per Systemic Lupus International Collaborating
Clinics (SLICC) 2012-criteria.
Exclusion criteria
1. Primary hemophagocytic lymphohistiocytosis (pHLH) documented by either the
presence of a known causative genetic mutation or abnormal perforin expression
or CD107a degranulation assay as described with pHLH or by the presence of
family history.
2. Confirmed malignancy. Note: patients with a suspected malignancy should have
mononuclear cells typed by flow cytometry and/or tissue biopsy, as applicable,
to rule out malignancy.
3. Treatment with canakinumab, Janus kinase (JAK) inhibitors, tumor necrosis
factor (TNF) inhibitors and tocilizumab at the time of emapalumab initiation.
4. Ongoing treatment with anakinra at a dose above 4 mg/kg/day at time of
emapalumab initiation.
5. Patients treated with etoposide for MAS in the last 1 month.
6. Presence of any medical or psychological condition or laboratory result that
in the opinion of the Investigator can interfere with the patient's ability to
comply with the protocol requirements or makes the patient not appropriate for
inclusion to the study and treatment with emapalumab.
7. Foreseeable inability to cooperate with given instructions or study
procedures.
8. Clinically active mycobacteria (typical and atypical), Histoplasma
Capsulatum, or Salmonella infections.
9. Evidence of leishmania infections.
10. Evidence of latent TB.
11. History of hypersensitivity or allergy to any component of the study drug.
12. Receipt of a Bacillus Calmette-Guerin (BCG) vaccine within 12 weeks prior
to Screening.
13. Receipt of a live or attenuated live (other than BCG) vaccine within 4
weeks prior to Screening.
14. Pregnancy or lactating female patients.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-516153-52-00 |
| EudraCT | EUCTR2021-001577-24-NL |
| ClinicalTrials.gov | NCT05001737 |
| CCMO | NL78647.041.21 |