A Phase 2 interventional study of Emapalumab in Macrophage Activation Syndrome, Lymphohistiocytosis, Hemophagocytic and Arthritis, Juvenile, sponsored by Swedish Orphan Biovitrum. Completed at 5 sites in 5 countries. Open to participants aged 0 Years and older. Per ClinicalTrials.gov, last updated 2022-05-17.
Sponsored by Swedish Orphan Biovitrum · Phase 2, Interventional, and Treatment
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Macrophage Activation Syndrome (MAS) is a rare, life-threatening condition characterized by uncontrolled hyperinflammation which may develop on the background of systemic Juvenile Idiopathic Arthritis (sJIA) or Adult-onset Still's Disease (AOSD). Emapalumab is a monoclonal antibody neutralizing interferon-gamma (IFN-gamma), a key cytokine which contributes to the inflammation and tissue damage seen in MAS. The purpose of this study is to assess the safety, tolerability and efficacy of emapalumab in sJIA or AOSD participants developing MAS, presenting an inadequate response to high dose glucocorticoid treatment.
20 studies on the registry are indexed under Macrophage Activation Syndrome; 4 are open to participants now.
This study's enrollment of 14 is below the median of 33 across 11 interventional studies indexed under Macrophage Activation Syndrome.
Browse Macrophage Activation Syndrome studies →Swedish Orphan Biovitrum is the lead sponsor of 82 studies on the registry; 6 are open to participants now.
Of its 17 completed or terminated interventional studies of FDA-regulated products, 15 (88%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Drug: Emapalumab
Emapalumab was administered at an initial dose of 6 mg/kg by intravenous infusion. Emapalumab treatment continued at a dose of 3 mg/kg, every 3 days until study day 15, and then twice-a-week for an additional 2 weeks, i.e., until study day 28. The emapalumab regimen could be adapted (the frequency between infusions shortened, the dose increased, or the treatment prolonged beyond 4 weeks) upon assessment of a favourable benefit-risk profile. There was a 4-week off-drug follow-up period (up to Week 8).
Also known as: Gamifant
Incidence, Severity, Causality, and Outcomes of AEs (Serious and Nonserious)
Time frame: Up to Week 8
Evolution of Laboratory Parameters
Shifts from baseline in the following MAS-relevant laboratory parameters are reported: * Leukocytes * Platelets * Lactate dehydrogenase (LDH) * Alanine aminotransferase (ALT) * Aspartate aminotransferase (AST) * Ferritin * C-reactive protein * Activated partial thromboplastin time (aPTT) * Prothrombin time * D-dimer * Fibrinogen
Time frame: Up to Week 8
Number of Participants Withdrawn Due to Safety Reasons
Time frame: Up to Week 8
Number of Participants Achieving MAS Remission at Week 8 After Initiation of Emapalumab Treatment
Remission from MAS was evaluated according to the following criteria: Resolution of clinical signs and symptoms according to the investigator (MAS clinical signs and symptoms activity score ≤ 1) and Normalization of laboratory parameters relevant to MAS, as follows: * WBC count and platelet count above the LLN. * LDH below 1.5 × the ULN. * ALT and AST both below 1.5 × the ULN. * Fibrinogen higher than 100 mg/dL. * Ferritin levels decreased by at least 80 % from values at screening or baseline (whichever was higher) or below 2000 ng/mL, whichever was lower.
Time frame: Week 8
Time to First MAS Remission
Time frame: Up to Week 8
Number of Participants for Whom Glucocorticoids Could be Permanently Tapered at Any Time During the Study
Permanently tapering by at least 50% of the equivalent dose of prednisone. This was defined as achieving reduction of 50% of the baseline dose \[SD0\] and maintaining the reduction until the end of study).
Time frame: Up to Week 8
Time to Achievement of Permanent Glucocorticoids Tapering
Time to achievement of permanent glucocorticoid tapering by at least 50% of the equivalent dose of prednisone administered at emapalumab treatment start.
Time frame: Up to Week 8
Survival Time
Number of participants alive at the end of the study
Time frame: Up to Week 8
Number of Participants Withdrawn From the Study Due to Lack of Efficacy
Number of participants withdrawn from the study due to lack of efficacy
Time frame: Up to Week 8
Levels of Emapalumab Concentration
On all infusion days, PK samples were collected before the infusion start and between 15 and 30 minutes after infusion completion. In addition, following the first emapalumab infusion, PK samples were collected approximately 24 and 48 hours post-infusion, and following the second emapalumab infusion, PK samples were collected approximately 48 hours post-infusion. Upon treatment completion, PK samples were collected on all non-infusion visits until the 4-week follow-up visit/EOS.
Time frame: Data from the following time points are presented: SD0 (pre- and post-dose), Week 4 Visit 2 (pre- and post-dose), and 4-week follow-up visit/EoS.
Pharmacodynamic Parameters
Levels of total INF-gamma, CXCL9 and CXCL10
Time frame: Up to Week 8
Number of Participants Who Demonstrated a Presence of Circulating Antibodies Against Emapalumab to Determine Immunogenicity
The presence of circulating antibodies against emapalumab was inferred by positive results for anti-drug antibodies (ADAs).
Time frame: Up to Week 8
| Milestone | All Treated Population |
|---|---|
| Started | 14 |
| Completed | 14 |
| Not completed | 0 |
| Participants | All Treated Population |
|---|---|
| Number of participants with a TEAE | 13 |
| Number of participants with a serious TEAE | 6 |
| Number of participants with a severe TEAE | 2 |
| Number of participants with a moderate TEAE | 10 |
| Number of participants with a mild TEAE | 13 |
| Number of participants with a TEAE related to emapalumab | 4 |
| Number of participants with a TEAE unrelated to emapalumab | 13 |
| Number of participants with a TEAE with an outcome of recovered/resolved | 13 |
| Number of participants with a TEAE with an outcome of not recovered/not resolved | 3 |
| Number of participants with a TEAE with an outcome of recovering/resolving | 1 |
| Number of participants with a TEAE with an outcome of unknown | 1 |
Shifts from baseline in the following MAS-relevant laboratory parameters are reported: * Leukocytes * Platelets * Lactate dehydrogenase (LDH) * Alanine aminotransferase (ALT) * Aspartate aminotransferase (AST) * Ferritin * C-reactive protein * Activated partial thromboplastin time (aPTT) * Prothrombin time * D-dimer * Fibrinogen
| Participants | All Treated Population |
|---|---|
| Leukocytes: From a high value at baseline to a value within the reference range at Week 8 | 2 |
| Leukocytes: From a low value at baseline to a value within the reference range at Week 8 | 4 |
| Leukocytes: From a low value at baseline to a high value at Week 8 | 2 |
| Platelets: From a high value at baseline to a value within the reference range at Week 8 | 1 |
| Platelets: From a low value at baseline to a value within the reference range at Week 8 | 6 |
| Platelets: From a low value at baseline to a high value at Week 8 | 3 |
| LDH: From a high value at baseline to a value within the reference range at Week 8 | 6 |
| ALT: From a high value at baseline to a value within the reference range at Week 8 | 10 |
| ALT: From a high value at baseline to a low value at Week 8 | 1 |
| AST: From a high value at baseline to a value within the reference range at Week 8 | 11 |
| Ferritin: From a high value at baseline to a value within the reference range at Week 8 | 11 |
| Ferritin: From a high value at baseline to a low value at Week 8 | 2 |
| C-reactive protein: From a high value at baseline to a value within the reference range at Week 8 | 9 |
| aPTT: From a high value at baseline to a value within the reference range at Week 8 | 1 |
| aPTT: From a high value at baseline to a low value at Week 8 | 1 |
| aPTT: From a value within the reference range at baseline to a low value at Week 8 | 3 |
| aPTT: From a low value at baseline to a value within the reference range at Week 8 | 1 |
| aPTT: From a low value at baseline to a high value at Week 8 | 1 |
| Prothrombin time: From a high value at baseline to a value within the reference range at Week 8 | 5 |
| Prothrombin time: From a high value at baseline to a low value at Week 8 | 1 |
| Prothrombin time: From a value within the reference range at baseline to a low value at Week 8 | 3 |
| Prothrombin time: From a low value at baseline to a value within the reference range at Week 8 | 1 |
| D-dimer: From a high value at baseline to a value within the reference range at Week 8 | 8 |
| Fibrinogen: From a high value at baseline to a value within the reference range at Week 8 | 1 |
| Fibrinogen: From a value within the reference range at baseline to a high value at Week 8 | 1 |
| Fibrinogen: From a low value at baseline to a value within the reference range at Week 8 | 5 |
| Fibrinogen: From a low value at baseline to a high value at Week 8 | 1 |
| Participants | All Treated Population |
|---|---|
| Number of Participants Withdrawn Due to Safety Reasons | 0 |
Remission from MAS was evaluated according to the following criteria: Resolution of clinical signs and symptoms according to the investigator (MAS clinical signs and symptoms activity score ≤ 1) and Normalization of laboratory parameters relevant to MAS, as follows: * WBC count and platelet count above the LLN. * LDH below 1.5 × the ULN. * ALT and AST both below 1.5 × the ULN. * Fibrinogen higher than 100 mg/dL. * Ferritin levels decreased by at least 80 % from values at screening or baseline (whichever was higher) or below 2000 ng/mL, whichever was lower.
| Participants | All Treated Population |
|---|---|
| Number of Participants Achieving MAS Remission at Week 8 After Initiation of Emapalumab Treatment | 11 |
| days | All Treated Population |
|---|---|
| Time to First MAS Remission | 25 (19 to 56) |
Permanently tapering by at least 50% of the equivalent dose of prednisone. This was defined as achieving reduction of 50% of the baseline dose \[SD0\] and maintaining the reduction until the end of study).
| Participants | All Treated Population |
|---|---|
| Number of Participants for Whom Glucocorticoids Could be Permanently Tapered at Any Time During the Study | 12 |
Time to achievement of permanent glucocorticoid tapering by at least 50% of the equivalent dose of prednisone administered at emapalumab treatment start.
| days | All Treated Population |
|---|---|
| Time to Achievement of Permanent Glucocorticoids Tapering | 14.5 (4 to 28) |
Number of participants alive at the end of the study
| Participants | All Treated Population |
|---|---|
| Survival Time | 14 |
Number of participants withdrawn from the study due to lack of efficacy
| Participants | All Treated Population |
|---|---|
| Number of Participants Withdrawn From the Study Due to Lack of Efficacy | 0 |
On all infusion days, PK samples were collected before the infusion start and between 15 and 30 minutes after infusion completion. In addition, following the first emapalumab infusion, PK samples were collected approximately 24 and 48 hours post-infusion, and following the second emapalumab infusion, PK samples were collected approximately 48 hours post-infusion. Upon treatment completion, PK samples were collected on all non-infusion visits until the 4-week follow-up visit/EOS.
| μg/L | All Treated Population |
|---|---|
| Study Day 0 (pre-dose) | 5455.444 ± 19985.0660 |
| Study Day 0 (post-dose) | 104740.254 ± 20994.1054 |
| Week 4 Visit 2 (pre-dose) | 115472.076 ± 58676.7953 |
| Week 4 Visit 2 (post-dose) | 212900.657 ± 87466.3031 |
| 4-week follow-up Visit/EoS | 46447.462 ± 33657.0174 |
Levels of total INF-gamma, CXCL9 and CXCL10
| ng/L | All Treated Population: Study Day 0 | All Treated Population: 4-week Follow-up Visit/EoS |
|---|---|---|
| CXCL9 | 21986.010 ± 29405.8787 | 255.654 ± 596.4149 |
| CXCL10 | 7935.418 ± 9115.2857 | 639.102 ± 1058.9589 |
| Total IFN-γ | 425.528 ± 1191.8391 | 2132.656 ± 2967.4920 |
The presence of circulating antibodies against emapalumab was inferred by positive results for anti-drug antibodies (ADAs).
| Participants | All Treated Population |
|---|---|
| Number of Participants Who Demonstrated a Presence of Circulating Antibodies Against Emapalumab to Determine Immunogenicity | 0 |
Collected over Adverse events were recorded in patients from Study Day 0 (the day of the first emapalumab administration), during emapalumab treatment, and up to and including the 4-week follow-up visit/end of study (a minimum duration of 56 days). All adverse events were followed up for outcome at end of study; all serious adverse events were followed up until resolution.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| All Treated Population | 0/14 (0%) | 6/14 (42.9%) | 13/14 (92.9%) |
| Event | All Treated Population |
|---|---|
| Cardiopulmonary failureCardiac disorders | 1/14 |
| Intracardiac thrombusCardiac disorders | 1/14 |
| Juvenile myoclonic epilepsyNervous system disorders | 1/14 |
| PericarditisCardiac disorders | 1/14 |
| Pneumatosis intestinalisGastrointestinal disorders | 1/14 |
| RashSkin and subcutaneous tissue disorders | 1/14 |
| Still's diseaseMusculoskeletal and connective tissue disorders | 1/14 |
| ThrombocytopeniaBlood and lymphatic system disorders | 1/14 |
| Cytomegalovirus infection reactivationInfections and infestations | 1/14 |
| Event | All Treated Population |
|---|---|
| RashSkin and subcutaneous tissue disorders | 4/14 |
| DiarrhoeaGastrointestinal disorders | 3/14 |
| Cytomegalovirus infection reactivationInfections and infestations | 3/14 |
| HypertensionVascular disorders | 3/14 |
| HyperglycaemiaMetabolism and nutrition disorders | 3/14 |
| HeadacheNervous system disorders | 2/14 |
| Injection site reactionGeneral disorders | 2/14 |
| Acanthosis nigricansSkin and subcutaneous tissue disorders | 1/14 |
| Dermatitis diaperSkin and subcutaneous tissue disorders | 1/14 |
| Dry skinSkin and subcutaneous tissue disorders | 1/14 |
| Age, Categorical(Participants) | All Enrolled Participants |
|---|---|
| <=18 years | 13 |
| Between 18 and 65 years | 1 |
| >=65 years | 0 |
| Age, Continuous(years) | All Enrolled Participants |
|---|---|
| Mean | 9.9 ± 6.6 |
| Sex: Female, Male(Participants) | All Enrolled Participants |
|---|---|
| Female | 10 |
| Male | 4 |
| Race (NIH/OMB)(Participants) | All Enrolled Participants |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 2 |
| White | 11 |
| More than one race | 0 |
| Unknown or Not Reported | 1 |
| Region of Enrollment(Participants) | All Enrolled Participants |
|---|---|
| United States | 3 |
| Italy | 7 |
| United Kingdom | 2 |
| Spain | 1 |
| France | 1 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Feb 2018 to primary completion in May 2020, 26 months.
Results were first posted in Jan 2022, 1 year 8 months after primary completion. A results delay was requested in May 2021.
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Studies of the drug tested here: Emapalumab
Macrophage Activation Syndrome →