rheumato-immune disease-associated hemophagocytic lymphohistiocytosis /macrophage activation syndrome
Conditions
Interventions
Experimental: Plonmarlimab:Phase 1: According to dose escalation principle, starting from the 6 mg/kg dose group and increasing to the 10 mg/kg dose group. During the DLT evaluation period (D1 to D14)
Sponsors
Beijing Friendship Hospital,Capital Medical University
Eligibility
Sex/Gender
All
Age
16 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Subjects aged 16 to 80 years old, regardless of gender. 2. Subjects are willing to participate in this study and sign informed consent voluntarily. For subjects under the age of 16 (including) and under 18 years old, the informed consent is required to be signed in person by the subject and the guardian of the subject. 3. Diagnosis of hemophagocytic lymphohistiocytosis (HLH) according to the HLH 2004 diagnostic criteria. 4. Diagnosis of rheumatic immune diseases, including: a) Systemic juvenile idiopathic arthritis (sJIA), meeting the ILAR-SJIA classification criteria OR b) Adult Onset Still Disease (AOSD), meeting the Yamaguchi criteria OR c) Systemic lupus erythematosus (SLE), meeting ACR criteria (1997) OR d) Other systemic rheumatic and immune diseases. 5. The subject (including the subject's sex partner) had no pregnancy plan and voluntarily took contraceptive measures within 28 days from the screening period to the last dose.
Exclusion criteria
Exclusion criteria: 1. Diagnosis of suspected or confirmed primary HLH. 2. Subject: a) were receiving TNF, canakinumab, Janus kinase inhibitor (JAKi), and tocilizumab at baseline visit; b) being treated with anakinra at a dose >= 4 mg/kg at baseline visit; c) received etoposide (VP 16) for MAS within 1 month before baseline visit; d) increase the dose or variety of non-biological agents (e.g., immunosuppressants, immunomodulators, antimalarials) used to treat rheumatic immune diseases within 3 days prior to baseline visit, unless the investigator determines expected efficacy and discontinue use prior to baseline. 3. History of allergy to any component of the study drug. 4. Underlying lung diseases that significantly affect lung function. 5. History of acute myocardial infarction or unstable angina pectoris, severe arrhythmia in the past 6 months; New York Cardiac Function Scale (NYHA) Grade III - Grade IV. 6. A history of malignancy (with or without treatment) within the past 5 years, except for basal cell or squamous cell carcinoma of the skin that has been successfully treated. 7. The subject has a clinically significant acute or chronic disease that is clinically significant and unstable or not effectively controlled, or a planned medical/surgical procedure; Or put the subject at undue risk or affect the subject's ability to participate independently in the study. 8. Uncontrolled infection diagnosed by investigator during the screening period. 9. Active mycobacterium tuberculosis infection. 10. Positive serology for HBsAg, HBcAb, HCV-Ab, HIV-Ab and TPPA. If HBcAb test is positive, hepatitis B DNA test is added, and HBV-DNA higher than the lower limit of detection is excluded. 11. Cr or BUN >= 1.5 times of ULN; Or eGFR <= 60 ml/min before screening. 12. Subjects with past or ongoing hematological diseases (including but not limited to: myelofibrosis, aplastic anemia, leukemia, lymphoma, etc.). 13. Subjects plan to undergo surgery or have a history of other diseases, abnormalities in laboratory tests, or other conditions are determined by the investigator to be ineligible for participation in the study. 14. History of vital organ transplantation (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation. 15. Pregnant or lactating women. 16. Participated in any clinical trials or used invasive investigational medical devices in the 3 months prior to enrollment, or is currently enrolled in an interventional study. 17. Received live vaccination within 30 days prior to screening. 18. Detection of drug abusers through urine drug screening. 19. Evidence of alcohol abuse history or ongoing abuse in the three months prior to screening. 20. The investigator considers the subject unfit to participate in the clinical study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Stage 1,Safety endpoint:Adverse events, physical examination, vital signs, 12-lead ECG, safety laboratory tests, respiratory related tests.;Stage 2: Primary efficacy endpoint, overall response rate (ORR) : Overall response includes complete response (CR) or partial response (PR).; | — |
Secondary
| Measure | Time frame |
|---|---|
| pharmacokinetic endpoint: serum drug concentration and pharmacokinetic parameters after administration.;Phase I: Immunogenicity endpoint the proportion of subjects with anti-drug antibody and titer;Stage 1: Overall Response Rate (ORR) : The overall Response includes Complete Response (CR) or Partial Response (PR);Survival rate at the end of week 8 and follow-up period;Complete Response (CR) rate;Partial Response (PR) rate;Clinical Complete Response (cCR) rate; Clinical overall response (cOR) rate: Clinical overall response includes clinical complete response (cCR) or partial response (PR);;Time to first achieve a clinical overall response;Duration of overall clinical response;MAS remission rate;The time when MAS remission is first achieved;Duration of MAS remission;Percentage of subjects with glucocorticoid dose reduced by 50% or more from baseline;Percentage change in glucocorticoid dose from baseline at each visit;Stage II,Safety endpoint:Adverse events, physical examination, vital signs, 12-lead ECG, safety laboratory tests, respiratory related tests;Efficacy biomarkers : serum CCL17, IL-6, IL-18, IFN-?, and GM-CSF levels and changes from baseline after administration;Serum sCD63 levels and changes from baseline after administration; | — |
Countries
China
Contacts
Public ContactZhao Wang
Beijing Friendship Hospital,Capital Medical University
Outcome results
None listed