RECRUITING

Efficacy and Safety Study of Narsoplimab in Pediatric Patients With High-Risk Hematopoietic Stem Cell Transplant TMA

Conditions

Thrombotic Microangiopathies Hematopoietic Stem Cell Transplantation TMA HSCT Pediatric BMT OMS721 Narsoplimab

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to evaluate the safety and efficacy of narsoplimab in pediatric patients with thrombotic microangiopathies (TMA) following hematopoietic stem cell transplant (HSCT).

Official Title

A Phase 2 Study Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Narsoplimab in Pediatric Patients (28 Days to ≤ 18 Years of Age.) With High-Risk Hematopoietic Stem Cell Transplant Thrombotic Microangiopathy

Quick Facts

Study Start:2023-05-01

Study Completion:2025-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05855083

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:28 Days to 17 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD

Inclusion Criteria	Exclusion Criteria
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 hematopoietic stem cell transplant for the treatment of benign or malignant disease. 5. Have a diagnosis of HSCT-TMA defined as meeting both of the following criteria: * Platelet count \< 50,000/mL 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 * 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 pediatric patients, defined as starting at onset of menses), must agree to practice a highly effective method of birth control throughout 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. 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. 10. Have a positive test by antigen 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. Patient or one or more of the patient's parents or legal guardians are is an employee or an immediate family member of Omeros, the Clinical Research Organization (CRO), an Investigator, or a study staff 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.

Inclusion Criteria

Exclusion Criteria

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 hematopoietic stem cell transplant for the treatment of benign or malignant disease.
5. Have a diagnosis of HSCT-TMA defined as meeting both of the following criteria:
* Platelet count \< 50,000/mL 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
* 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 pediatric patients, defined as starting at onset of menses), must agree to practice a highly effective method of birth control throughout 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.
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.
10. Have a positive test by antigen 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. Patient or one or more of the patient's parents or legal guardians are is an employee or an immediate family member of Omeros, the Clinical Research Organization (CRO), an Investigator, or a study staff 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.

Contacts and Locations

Study Contact

Omeros Clinical Trial Information

CONTACT

206-676-5000

ctinfo@omeros.com

Study Locations (Sites)

Omeros Investigational Site

San Diego, California, 92024

United States

Omeros Investigational Site

Gainesville, Florida, 32608

United States

Omeros Investigational Site

Boston, Massachusetts, 02215

United States

Omeros Investigational Site

Saint Louis, Missouri, 63104

United States

Omeros Investigational Site

New York, New York, 10065

United States

Omeros Investigational Site

Valhalla, New York, 10595

United States

Omeros Investigational Site

Houston, Texas, 77030

United States

Omeros Investigational Site

Seattle, Washington, 98105

United States

Collaborators and Investigators

Sponsor: Omeros Corporation

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-05-01

Study Completion Date2025-12

Study Record Updates

Study Start Date2023-05-01

Study Completion Date2025-12

Terms related to this study

Keywords Provided by Researchers

TMA
HSCT
Pediatric
BMT
OMS721
Narsoplimab

Additional Relevant MeSH Terms

Thrombotic Microangiopathies
Hematopoietic Stem Cell Transplantation