A Phase 2 Study Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Narsoplimab in Paediatric Patients (28 Days to 18 Y.O.) with High Risk Haematopoietic Stem Cell Transplant Thrombotic Microangiopathy
- Conditions
- thrombotic microangiopathies (TMA)100188651002766510047066
- Registration Number
- NL-OMON56242
- Lead Sponsor
- Omeros Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 2
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, 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.
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 (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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method