A Phase 2 Study on Narsoplimab in Paediatric Patients with High Risk Haematopoietic Stem Cell Transplant Thrombotic Microangiopathy
- Conditions
- Thrombotic microangiopathies following haematopoietic stem cell transplantMedDRA version: 20.0Level: HLGTClassification code 10064477Term: Coagulopathies and bleeding diatheses (excl thrombocytopenic)System Organ Class: 10005329 - Blood and lymphatic system disordersMedDRA version: 20.0Level: PTClassification code 10043645Term: Thrombotic microangiopathySystem Organ Class: 10005329 - Blood and lymphatic system disordersMedDRA version: 20.0Level: HLTClassification code 10053567Term: CoagulopathiesSystem Organ Class: 10005329 - Blood and lymphatic system disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2021-002727-38-HU
- Lead Sponsor
- Omeros Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 18
1. Age at least 28 days and less than 18 years prior to informed consent (Visit 0).
2. Have informed consent from at least one parent or legal guardian as required by local law and regulation. Patient informed consent will be required if the patient has reached the local legal age of majority.
3. Assent from patients as required by local law and regulation.
4. Have received an allogeneic haematopoietic stem cell transplant for the treatment of non-malignant or malignant disease. All donor cell sources are allowed (i.e., matched, mismatched, and haploidentical; related and unrelated; bone marrow, peripheral blood stem cells, and umbilical cord blood).
5. Have a diagnosis of HSCT-TMA defined as having both of the following:
-Platelet count < 50,000/µL or a decrease in platelet count > 50% from the highest value obtained following transplant.
-Evidence of microangiopathic hemolysis (presence of schistocytes, serum lactate dehydrogenase [LDH] > upper limit of normal ([ULN], or haptoglobin < lower limit of normal [LLN])
6. Have at least one of the following HSCT-TMA high-risk criteria:
- HSCT-TMA persistence > 2 weeks following modification of calcineurin inhibitors or sirolimus
OR
- Have evidence of high-risk HSCT-TMA defined as at least one of the following:
- Spot protein/creatinine ratio > 2 mg/mg
- Serum creatinine > 1.5 x the creatinine level prior to TMA development
- Biopsy-proven gastrointestinal TMA
- TMA-related neurological abnormality (e.g., confusion, stroke, transient ischemic attack [TIA] or seizures)
- Pericardial or pleural effusion without alternative explanation
- Pulmonary hypertension without alternative explanation
- Have Grade III or Grade IV graft-versus-host disease (GVHD) or, in the opinion of the Investigator, risk for development of Grade III or Grade IV GVHD if immunosuppression were to be modified
- Have elevated serum C5b-9 (> 244 ng/mL)
7. If sexually active and of childbearing potential (for female paediatric patients, defined as starting at onset of menses), must agree to practice a highly effective method of birth control throughout the study drug treatment and for at least 12 weeks after the last dose of study drug, such method of birth control defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence (abstinence is acceptable when it is in line with the patient's preferred and usual lifestyle and is defined as
complete abstinence of sexual intercourse, not periodic abstinence or withdrawal), or vasectomized partner.
8. Male patients must be willing to avoid fathering children for at least 12 weeks following the last dose of study medication.
Are the trial subjects under 18? yes
Number of subjects for this age range: 18
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. All treatments for HSCT-TMA are allowed except eculizumab, ravulizumab, and defibrotide within 3 months prior to informed consent, unless failure of therapy can be documented.
a. Patients may not be on eculizumab, ravulizumab, or defibrotide for any indication at screening.
2. Have Shiga toxin-producing Escherichia coli haemolytic uraemic syndrome (STEC-HUS). Test results obtained within 28 days prior to informed consent may be used.
3. Have ADAMTS13 activity < 10%. Test results obtained within 28 days prior to informed consent may be used.
4. Have a severe, uncontrolled systemic bacterial or fungal infection requiring antimicrobial therapy or a severe uncontrolled viral infection (as determined by the investigator); prophylactic antimicrobial therapy administered as standard of care is allowed.
5. Have malignant hypertension (blood pressure [BP] > 99th percentile plus 5 mmHg with bilateral hemorrhages or cotton-wool” exudates on fundoscopic examination).
6. Due to conditions other than HSCT-TMA, have a poor prognosis with a life expectancy of less than 3 months in the opinion of the Investigator.
7. If pregnant or lactating
8. Have received treatment with an investigational drug or device within 4 weeks of entering study.
9. Have abnormal liver function tests defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times ULN within 28 days prior to informed consent through prior to the first dose.
10. Have a positive test by antigen, antibody, or polymerase chain reaction (PCR) for human immunodeficiency virus (HIV); if negative within 28 days prior to informed consent, the test does not need to be repeated.
11. Patients or their parents or legal guardians are an employee of Omeros, Clinical Research Organization (CRO), an Investigator, a study staff member, or an immediate family member.
12. Have a known hypersensitivity to any constituent of the product.
13. Presence of any condition that the Investigator believes would put the patient at risk.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Describe the 100-day survival rate following high risk HSCT-TMA diagnosis.;Secondary Objective: - Evaluate the safety and tolerability of intravenous (IV) administration of narsoplimab.<br>- Describe the efficacy of narsoplimab by responder rate; survival at 52 weeks; and mean, median, and overall survival rates.<br>- Evaluate peak and trough PK of IV narsoplimab.<br>- Immunogenicity will be evaluated.<br>- Anti-drug antibody (ADA) responses will be summarized by treatment group and will be evaluated.;Primary end point(s): 100-day survival rate from date of HSCT-TMA diagnosis;Timepoint(s) of evaluation of this end point: 100 days
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Survival at 52 weeks and median, mean, and overall survival from date of TMA diagnosis<br>- Narsoplimab peak and trough PK and concomitant lectin pathway activation measured by ex vivo assay<br>- Safety will be evaluated by adverse events (AEs) and laboratory measures<br>- Anti-drug antibody response<br>- Responder rate based on clinical response criteria;Timepoint(s) of evaluation of this end point: 52 weeks