Emapalumab for Macrophage Activation Syndrome

Phase-Based Progress Estimates
2
Effectiveness
3
Safety
UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA
Macrophage Activation Syndrome+8 More
Emapalumab - Drug
Eligibility
Any Age
All Sexes
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Study Summary

Evaluate Efficacy, Safety and Tolerability, PK and PD of Emapalumab in Children and Adults With MAS in Still's or SLE

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Eligible Conditions

  • Macrophage Activation Syndrome
  • Secondary Hemophagocytic Lymphohistiocytosis
  • Still Disease
  • AOSD
  • Systemic Lupus Erythematosus (SLE)
  • SJIA
  • MAS

Treatment Effectiveness

Effectiveness Progress

2 of 3
This is further along than 85% of similar trials

Other trials for Macrophage Activation Syndrome

Study Objectives

This trial is evaluating whether Emapalumab will improve 1 primary outcome, 9 secondary outcomes, and 16 other outcomes in patients with Macrophage Activation Syndrome. Measurement will happen over the course of 8 weeks.

8 weeks
Proportion of subjects with complete response (CR) at Week 8 after first administration of emapalumab
Year 1
MAS recurrence at anytime after achievement of CR
Year 1
Adverse Events (AEs) (serious and non-serious).
GCs tapering to a dose below 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 whichever occurs first
GCs tapering to ≤1mg/kg/day of PDN equivalent at any time during the study.
Laboratory parameters
Proportion of subjects with overall response as defined by CR or PR
Study interruption due to safety reasons
Survival time
Time to achieve GCs tapering as defined above.
Time to first Complete Remission
Time to first overall response as defined by CR or PR
Withdrawal from the study due to lack of response as per Investigator decision
Year 1
PD endpoints per cohort: chemokines
PD endpoints per cohort: free IFN-γ and total IFNγ
PD endpoints per cohort: sCD25)
PK endpoints
PK endpoints CEOI
PK endpoints: CL
PK endpoints: MRTlast and MRTinf
PK endpoints: Vss
PK endpoints: λz
Year 1
Patient reported outcomes : PedsQL™;
Patient reported outcomes: Clinician Global Impression of Severity
Patient reported outcomes: Patient/Parent Global Impression of Severity
Year 1
Immunogenicity endpoints

Trial Safety

Safety Progress

3 of 3
This is further along than 85% of similar trials

Other trials for Macrophage Activation Syndrome

Side Effects for

Enrolled-CU Cohort
Rhinitis
29%
Pseudomonal sepsis
29%
Condition aggravated
29%
Hypokalaemia
29%
Hypomagnesaemia
29%
Septic shock
14%
Pyrexia
14%
Hypercalcaemia
14%
Graft versus host disease in skin
14%
Blood stem cell transplant failure
14%
Food allergy
14%
Hypertension
14%
Sickle cell trait
14%
Tracheitis
14%
Pleocytosis
14%
Pleural effusion
14%
Panniculitis
14%
Klebsiella test positive
14%
Enterocolitis haemorrhagic
14%
Seizure
14%
Respiratory failure
14%
Pulmonary oedema
14%
Staphylococcal sepsis
14%
Skin lesion
14%
Rash papular
14%
Gastroenteritis
14%
Pharyngitis
14%
Vomiting
14%
Klebsiella sepsis
14%
Hyponatraemia
14%
Hypocalcaemia
14%
Pancreatitis
14%
Adenovirus infection
14%
Rash
14%
Dermatitis
14%
Candida infection
14%
Respiratory distress
14%
Tracheobronchitis
14%
Device breakage
14%
Extremity necrosis
14%
Infusion related reaction
14%
Bradycardia
14%
Graft versus host disease
14%
Viral upper respiratory tract infection
14%
Acute kidney injury
14%
Atelectasis
14%
Pulmonary mass
14%
Hypotension
14%
Enterobacter sepsis
14%
Oral candidiasis
14%
Periorbital cellulitis
14%
Arthropod bite
14%
Subdural haematoma
14%
Acinetobacter test positive
14%
Hyperphosphataemia
14%
Metabolic acidosis
14%
Hypertrophic osteoarthropathy
14%
Anuria
14%
Oliguria
14%
Candida test positive
14%
Neuralgia
14%
Face oedema
14%
Torus fracture
14%
Ubiquinone decreased
14%
Papule
14%
Pneumonia cytomegaloviral
0%
Multiple organ dysfunction syndrome
0%
Gastroenteritis adenovirus
0%
Epstein-Barr virus infection
0%
Periorbital oedema
0%
Subdural hygroma
0%
Sinusitis bacterial
0%
Fluid overload
0%
Flank pain
0%
Musculoskeletal chest pain
0%
Transaminases increased
0%
Somnolence
0%
Major depression
0%
Still's disease
0%
Blood creatinine increased
0%
Stomatitis
0%
Inguinal hernia
0%
Pain
0%
Vision blurred
0%
Retinal disorder
0%
Ascites
0%
Bacille Calmette-Guerin scar reactivation
0%
Cytomegalovirus chorioretinitis
0%
Epstein-Barr viraemia
0%
Klebsiella bacteraemia
0%
Rhinovirus infection
0%
Staphylococcal infection
0%
Viral haemorrhagic cystitis
0%
Contusion
0%
BK polyomavirus test positive
0%
Hypernatraemia
0%
Hypercreatininaemia
0%
Hypoalbuminaemia
0%
Milk soy protein intolerance
0%
Bone pain
0%
Opisthotonus
0%
Enterovirus infection
0%
Engraftment syndrome
0%
Localised oedema
0%
Adenovirus test positive
0%
Cyanosis
0%
Abdominal distension
0%
Visceral pain
0%
Acute respiratory distress syndrome
0%
Dysphonia
0%
Gastroenteritis salmonella
0%
Vascular access complication
0%
Joint swelling
0%
Hyperplastic cholecystopathy
0%
Constipation
0%
Coombs positive haemolytic anaemia
0%
Neurological decompensation
0%
Macrocytosis
0%
Tongue ulceration
0%
Cytomegalovirus infection reactivation
0%
Urinary tract infection
0%
Engraft failure
0%
Unintentional medical device removal
0%
Fluid retention
0%
Circulatory collapse
0%
Cardiac arrest
0%
Eye movement disorder
0%
Diarrhoea
0%
Lip ulceration
0%
Catheter site pain
0%
Allergic transfusion reaction
0%
Complication of device insertion
0%
Fibrosis
0%
Cytomegalovirus test positive
0%
Acute graft versus host disease in skin
0%
Adverse event following immunisation
0%
Urinary tract infection bacterial
0%
Foot fracture
0%
Urine output decreased
0%
Hydrocephalus
0%
Separation anxiety disorder
0%
Cough
0%
Dyspnoea
0%
Epistaxis
0%
Lung infiltration
0%
Petechiae
0%
Dermatitis contact
0%
Hyperhidrosis
0%
Osteonecrosis
0%
Tachycardia
0%
Clostridium difficile colitis
0%
Increased tendency to bruise
0%
Hyperglycaemia
0%
Cardiac tamponade
0%
Thrombotic microangiopathy
0%
Right ventricular dysfunction
0%
Ear infection
0%
Respiratory syncytial virus infection
0%
Oedema peripheral
0%
Failure to thrive
0%
Enterococcal infection
0%
Acute respiratory failure
0%
Gianotti-Crosti syndrome
0%
Pericardial effusion
0%
Pulmonary alveolar haemorrhage
0%
Abdominal pain
0%
Febrile neutropenia
0%
Adrenal insufficiency
0%
Anaphylactic reaction
0%
Haematochezia
0%
Drug eruption
0%
Diverticulum
0%
Autoimmune hepatitis
0%
Xerosis
0%
Drug-induced liver injury
0%
Croup infectious
0%
Oesophageal candidiasis
0%
Burns first degree
0%
Transfusion reaction
0%
Aspartate aminotransferase increased
0%
Blood albumin decreased
0%
Hypophosphataemia
0%
Ocular hyperaemia
0%
Swelling face
0%
Irritability
0%
Skin disorder
0%
Skin laceration
0%
Pneumonia
0%
Maculopathy
0%
Hyperbilirubinaemia
0%
Folliculitis
0%
Gastroenteritis norovirus
0%
Alanine aminotransferase increased
0%
Blood immunoglobulin G decreased
0%
Arthralgia
0%
Hypotonia
0%
Rash macular
0%
Restlessness
0%
Renal failure
0%
Dysuria
0%
Pelvi-ureteric obstruction
0%
Lymphopenia
0%
Cestode infection
0%
Small intestinal obstruction
0%
Bronchiolitis
0%
Urosepsis
0%
Clostridium difficile infection
0%
Gastroenteritis viral
0%
Anaemia
0%
Gastroenteritis rotavirus
0%
Secondary adrenocortical insufficiency
0%
Nephrolithiasis
0%
Neutropenia
0%
Iron deficiency anaemia
0%
Oral mucosal discolouration
0%
Gastric mucosa erythema
0%
Gastrointestinal haemorrhage
0%
Gastrooesophageal reflux disease
0%
Umbilical hernia
0%
Fatigue
0%
Influenza like illness
0%
Mucosal inflammation
0%
Hepatic steatosis
0%
Gait disturbance
0%
Graft versus host disease in gastrointestinal tract
0%
Graft versus host disease in liver
0%
Atypical mycobacterium test positive
0%
Allergy to immunoglobulin therapy
0%
Staphylococcal bacteraemia
0%
Enterococcal bacteraemia
0%
Otitis externa
0%
Upper respiratory tract infection
0%
BK virus infection
0%
Bacillus bacteraemia
0%
Cytomegalovirus infection
0%
Escherichia bacteraemia
0%
Human herpesvirus 6 infection reactivation
0%
Herpes simplex gastritis
0%
Pneumonia bacterial
0%
Skin bacterial infection
0%
Serratia bacteraemia
0%
Urinary tract infection viral
0%
Skin abrasion
0%
Femoral neck fracture
0%
Transplant dysfunction
0%
Human rhinovirus test positive
0%
Roseolovirus test positive
0%
Blood electrolytes abnormal
0%
Campylobacter test positive
0%
Clostridium test positive
0%
Mycobacterium test positive
0%
Neutrophil count decreased
0%
Norovirus test positive
0%
Pseudomonas test positive
0%
Dehydration
0%
Malnutrition
0%
Poor feeding infant
0%
Hypophagia
0%
Back pain
0%
Growth failure
0%
Muscle spasms
0%
Headache
0%
Musculoskeletal pain
0%
Osteopenia
0%
Epilepsy
0%
Nystagmus
0%
Subdural effusion
0%
Paraesthesia
0%
Tachypnoea
0%
Pulmonary haemorrhage
0%
Haemothorax
0%
Nasal congestion
0%
Nasal flaring
0%
Pneumothorax
0%
Sinus congestion
0%
Pruritus
0%
Rash maculo-papular
0%
Rash erythematous
0%
Dermatitis allergic
0%
Dry skin
0%
Skin exfoliation
0%
Hyperaemia
0%
Dental caries
0%
Rectal prolapse
0%
Arthritis
0%
Cholelithiasis
0%
Retinal ischaemia
0%
Influenza
0%
Drug reaction with eosinophilia and systemic symptoms
0%
Ear pain
0%
Pneumatosis intestinalis
0%
Myositis
0%
Sinusitis
0%
Oral pain
0%
Parainfluenzae virus infection
0%
Respirovirus test positive
0%
Oxygen saturation decreased
0%
Agitation
0%
Oropharyngeal pain
0%
Sleep apnoea syndrome
0%
Erythema
0%
Ingrowing nail
0%
Flushing
0%
Haemolytic anaemia
0%
Gastritis
0%
Oedema
0%
Lymphocytosis
0%
Duodenal ulcer
0%
Left ventricular hypertrophy
0%
Acute graft versus host disease in intestine
0%
Endocarditis
0%
Pneumonia pseudomonal
0%
Hypothyroidism
0%
Dry eye
0%
Nausea
0%
Pulmonary hypertension
0%
Shock
0%
Complication associated with device
0%
Meningitis enterococcal
0%
Herpes simplex test positive
0%
Scrotal swelling
0%
Sneezing
0%
Rash pruritic
0%
Urticaria
0%
Viral infection
0%
Blood alkaline phosphatase increased
0%
This histogram enumerates side effects from a completed 2021 Phase 2 & 3 trial (NCT02069899) in the Enrolled-CU Cohort ARM group. Side effects include: Rhinitis with 29%, Pseudomonal sepsis with 29%, Condition aggravated with 29%, Hypokalaemia with 29%, Hypomagnesaemia with 29%.

Trial Design

1 Treatment Group

Cohort 1 (sJIA and AOSD) and Cohort 2 (SLE)
1 of 1
Experimental Treatment

This trial requires 41 total participants across 1 different treatment group

This trial involves a single treatment. Emapalumab is the primary treatment being studied. Participants will all receive the same treatment. There is no placebo group. The treatments being tested are in Phase 3 and have had some early promising results.

Cohort 1 (sJIA and AOSD) and Cohort 2 (SLE)
Drug
MAS in the context of systemic juvenile idiopathic arthritis and adult onset Still's disease (sJIA and AOSD) or SLE
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Emapalumab
FDA approved

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: at any time after cr, up to 1 year
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly at any time after cr, up to 1 year for reporting.

Closest Location

UPMC Children's Hospital of Pittsburgh - Pittsburgh, PA

Eligibility Criteria

This trial is for patients born any sex of any age. There are 10 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
Inclusion criteria Run-in phase in all cohorts
Informed consent provided by the subject or by the subject s' legally authorized representative(s) with the assent of subjects who are legally capable of providing it, as required by local law.
Male and female subjects aged between 6 months and 80 years of age at the time of diagnosis of MAS.
MAS defined as per the criteria defined below for each cohort and requiring treatment with GCs.
Interventional phase in all cohorts
Informed consent provided by the subject or by the subject's legally authorized representative(s) with the assent of subjects who are legally capable of providing it, as as required by local law.
Male and female subjects aged between 6 months and 80 years of age at the time of diagnosis of active MAS.
Subjects 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 PDN 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 subjects of 30 kg or more, and at least 1g/day in adult MAS subjects). In case of rapid worsening of the subject's condition and/or laboratory parameters, as per Investigator judgment, inclusion may occur within less than 3 days from starting high dose GCs.
a. Febrile subjects presenting with ferritin > 684 ng/mL. b. and any 2 of: i. Platelet count ≤ 181 x109/L ii. AST-level > 48 U/L iii. Triglycerides > 156 mg/dL iv. Fibrinogen level ≤ 360 mg/dL
Female subjects of child-bearing potential willing to use highly effective methods of contraception from study drug initiation to 6 months after the last dose of study drug.

Patient Q&A Section

How many people get macrophage activation syndrome a year in the United States?

"Macrophage activation syndrome is not rare in the US. However, there is no specific disease or age group that is associated with a higher risk for this syndrome. Patients should be identified, counseled, and placed on the appropriate protocol depending on the type and severity of their MVS." - Anonymous Online Contributor

Unverified Answer

What are the signs of macrophage activation syndrome?

"MOF is an emergency for which prompt diagnosis is necessary. In order to avoid delays in diagnosis of MOF, it is necessary to consider systemic inflammatory response syndrome (SIRS) in addition to the diagnostic criteria for MOF." - Anonymous Online Contributor

Unverified Answer

What are common treatments for macrophage activation syndrome?

"Macrophage activation syndrome can be treated with immunosuppression including corticosteroids or plasma exchange. Immunoglobulin therapy can be used as an alternative medication in immunocompromised patients. Injection with mycoplasma hyopneumoniae or other live vaccines should be avoided as a precaution until results of further research are determined. It is very important to treat acute respiratory distress syndrome as soon as possible with oropharyngeal intubation, mechanical ventilation, and steroids in severe cases or extracorporeal membrane oxygenation if this is needed." - Anonymous Online Contributor

Unverified Answer

What is macrophage activation syndrome?

"MAC is distinct from other syndromes, owing to the predominance of monocytic (neutrophilic) and neutropenic (platelets-bound inflammatory) monocytes in the blood and (in some cases) bone marrow. The term MAd might be more appropriate, and should be applied to cases in which the monocytic and/or neutropenic monocytes are predominant in blood and/or bone marrow. The current criteria to help define, distinguish, and diagnose MAd are discussed and may be helpful for clinicians, investigators, and researchers." - Anonymous Online Contributor

Unverified Answer

What causes macrophage activation syndrome?

"Macrophage activation syndrome is an enigmatic disease with possible multi-factorial aetiology. More study is needed to determine whether cytokine blockade may affect the course or outcome of MACS." - Anonymous Online Contributor

Unverified Answer

Can macrophage activation syndrome be cured?

"The diagnosis of MAS is associated with excessive tissue destruction and excessive proliferation of lymphocytes, mainly T cells. Thus, there is an ideal candidate for treatment of MAS with immunotherapy." - Anonymous Online Contributor

Unverified Answer

What are the latest developments in emapalumab for therapeutic use?

"Emapalumab is a specific human monoclonal antibody that has been developed to block IL-1α activity and IFN-γ release. The biologic activity of IL-1α and IFN-γ is a major driving factor for inflammatory processes leading to tissue damage. Inhibition of the inflammatory processes by emapalumab results in reduced tissue damage. In this way, emapalumab could prevent or decrease inflammation-induced tissue damage and thus would be applicable for the treatment of inflammatory-related disorders such as acute severe skin reactions in inflammatory diseases. This is the very first clinical report for the use of emapalumab in inflammatory diseases." - Anonymous Online Contributor

Unverified Answer

How serious can macrophage activation syndrome be?

"In this retrospective study, MAAS was associated with low in-hospital mortality ratios; however, long-term outcomes were not as good as one might expect. Long-term survival seemed to be affected by age and underlying comorbidities." - Anonymous Online Contributor

Unverified Answer

What is the latest research for macrophage activation syndrome?

"Clinical trials use steroids and non-steroidal antiinflammatory drugs as treatment for MACS. There are several possible explanations for those treatments: (1) steroids are trying to reduce systemic inflammation; (2) non-steroidal anti-inflammatory drugs might try to alleviate pain and reduce itching; and (3) steroids might not work, but non-steroidal anti-inflammatory drugs might. More study is warranted." - Anonymous Online Contributor

Unverified Answer

Is emapalumab safe for people?

"Emapalumab is well tolerated overall and there are no treatment-related serious side effects, except for exacerbation of hepatitis B in one patient. There were no clinically meaningful changes to the pharmacokinetic profile of emapalumab in healthy subjects and no interaction with concomitant treatment could be identified." - Anonymous Online Contributor

Unverified Answer

Have there been other clinical trials involving emapalumab?

"There is a limited dataset of clinical trials involving emapalumab. Currently, it is being evaluated in four clinical trials including one in which it is given subcutaneously for induction and a third in which it is infused intravenously daily for 3 weeks followed by 5 weeks of break. An additional trial involves a dose-escalation design and is in phase I/II. In addition, the manufacturer has received authorization to conduct a Phase IIa trial, which will enroll patients with an existing high-risk/refractory CD20+ lymphoma. Finally, there is a Phase II trial of emapalumab for CD79a+/CD79b- B cell non-Hodgkin lymphoma." - Anonymous Online Contributor

Unverified Answer

What is the primary cause of macrophage activation syndrome?

"At present, it is unclear what primary cause is responsible for the increased production of cytokines. In some cases, there may be a genetic predisposition to develop a high cytokine response. Recent findings support further research focusing on the pathogenic mechanisms of macrophage activation syndrome, including the determination of its genetic basis." - Anonymous Online Contributor

Unverified Answer
Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.
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