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

Primary Purpose

Thrombotic Microangiopathies, Hematopoietic Stem Cell Transplantation

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Biological: narsoplimab
Sponsored by
Omeros Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Thrombotic Microangiopathies focused on measuring TMA, HSCT, Pediatric, BMT, OMS721, Narsoplimab

Eligibility Criteria

28 Days - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age at least 28 days and less than 18 years prior to informed consent (Visit 0). 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. Assent from patients as required by local law and regulation. Have received an allogeneic hematopoietic stem cell transplant for the treatment of benign or malignant disease. 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]) 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) 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. Male patients must be willing to avoid fathering children for at least 12 weeks following the last dose of study medication. Exclusion Criteria: 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. Have Shiga toxin-producing Escherichia coli haemolytic uraemic syndrome (STEC-HUS). Test results obtained within 28 days prior to informed consent may be used. Have ADAMTS13 activity < 10%. Test results obtained within 28 days prior to informed consent may be used. 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. Have malignant hypertension (blood pressure [BP] > 99th percentile plus 5 mmHg with bilateral hemorrhages or "cotton-wool" exudates on fundoscopic examination). 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. If pregnant or lactating. Have received treatment with an investigational drug or device within 4 weeks of entering study. Have abnormal liver function tests defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times ULN within 28 days prior to informed consent. 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. 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. Have a known hypersensitivity to any constituent of the product. Presence of any condition that the Investigator believes would put the patient at risk.

Sites / Locations

  • Omeros Investigational Site
  • Omeros Investigational Site
  • Omeros Investigational Site
  • Omeros Investigational Site
  • Omeros Investigational Site
  • Omeros Investigational SiteRecruiting
  • Omeros Investigational Site
  • Omeros Investigational Site
  • Omeros Investigational Site
  • Omeros Investigational Site
  • Omeros Investigational Site
  • Omeros Investigational Site
  • Omeros Investigational Site
  • Omeros Investigational Site
  • Omeros Investigational Site
  • Omeros Investigational Site
  • Omeros Investigational Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Narsoplimab single arm-treatment

Arm Description

Narsoplimab 4 mg/kg

Outcomes

Primary Outcome Measures

100-day survival rate following high-risk HSCT-TMA diagnosis.
Percentage of patients alive at 100 days following the diagnosis of high-risk HSCT-TMA

Secondary Outcome Measures

Number of participants with treatment-emergent adverse events assessed by CTCAE v5.0
Number and percentage of patients with treatment-emergent adverse events will be summarized by MedDRA system organ class and preferred term
Percentage of patients meeting protocol definition of clinical response
A responder is defined as a patient with HSCT-TMA who demonstrates improvement in laboratory TMA markers (platelet count and LDH) and clinical benefit (either improvement in organ function or reduction in transfusion burden)
52 week survival rate following high-risk HSCT-TMA diagnosis
Percentage of patients alive at 52 weeks following the diagnosis of high-risk HSCT-TMA
Overall survival following the diagnosis of high-risk HSCT-TMA
Median overall survival (days) following the diagnosis of high-risk HSCT-TMA by Kaplan-Meier estimate
Pharmacokinetics (PK) of multiple-dose administration of OMS721
PK parameters including maximum concentration and minimum (trough) concentration
Presence of anti-drug antibody (ADA)
Number and percentage of patient with at least one ADA positive sample

Full Information

First Posted
April 6, 2023
Last Updated
May 2, 2023
Sponsor
Omeros Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT05855083
Brief Title
Efficacy and Safety Study of Narsoplimab in Pediatric Patients With High-Risk Hematopoietic Stem Cell Transplant TMA
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 2023 (Anticipated)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Omeros Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).
Detailed Description
This is a Phase 2, uncontrolled, single-dosing regimen study in pediatric patients from 28 days to less than 18 years of age with high risk HSCT-TMA. At least 4 patients will be required from each of 3 age cohorts: 28 days to <2 years of age, 2 years to <12 years of age, and 12 years to <18 years of age. Treatment will be for 8 weeks and patients will be followed for up to 52 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thrombotic Microangiopathies, Hematopoietic Stem Cell Transplantation
Keywords
TMA, HSCT, Pediatric, BMT, OMS721, Narsoplimab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Narsoplimab single arm-treatment
Arm Type
Experimental
Arm Description
Narsoplimab 4 mg/kg
Intervention Type
Drug
Intervention Name(s)
Biological: narsoplimab
Other Intervention Name(s)
Narsoplimab
Intervention Description
Treatment with narsoplimab 4 mg/kg will be administered
Primary Outcome Measure Information:
Title
100-day survival rate following high-risk HSCT-TMA diagnosis.
Description
Percentage of patients alive at 100 days following the diagnosis of high-risk HSCT-TMA
Time Frame
100 days
Secondary Outcome Measure Information:
Title
Number of participants with treatment-emergent adverse events assessed by CTCAE v5.0
Description
Number and percentage of patients with treatment-emergent adverse events will be summarized by MedDRA system organ class and preferred term
Time Frame
52 weeks
Title
Percentage of patients meeting protocol definition of clinical response
Description
A responder is defined as a patient with HSCT-TMA who demonstrates improvement in laboratory TMA markers (platelet count and LDH) and clinical benefit (either improvement in organ function or reduction in transfusion burden)
Time Frame
52 weeks
Title
52 week survival rate following high-risk HSCT-TMA diagnosis
Description
Percentage of patients alive at 52 weeks following the diagnosis of high-risk HSCT-TMA
Time Frame
52 weeks
Title
Overall survival following the diagnosis of high-risk HSCT-TMA
Description
Median overall survival (days) following the diagnosis of high-risk HSCT-TMA by Kaplan-Meier estimate
Time Frame
52 weeks
Title
Pharmacokinetics (PK) of multiple-dose administration of OMS721
Description
PK parameters including maximum concentration and minimum (trough) concentration
Time Frame
52 weeks
Title
Presence of anti-drug antibody (ADA)
Description
Number and percentage of patient with at least one ADA positive sample
Time Frame
52 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
28 Days
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age at least 28 days and less than 18 years prior to informed consent (Visit 0). 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. Assent from patients as required by local law and regulation. Have received an allogeneic hematopoietic stem cell transplant for the treatment of benign or malignant disease. 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]) 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) 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. Male patients must be willing to avoid fathering children for at least 12 weeks following the last dose of study medication. Exclusion Criteria: 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. Have Shiga toxin-producing Escherichia coli haemolytic uraemic syndrome (STEC-HUS). Test results obtained within 28 days prior to informed consent may be used. Have ADAMTS13 activity < 10%. Test results obtained within 28 days prior to informed consent may be used. 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. Have malignant hypertension (blood pressure [BP] > 99th percentile plus 5 mmHg with bilateral hemorrhages or "cotton-wool" exudates on fundoscopic examination). 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. If pregnant or lactating. Have received treatment with an investigational drug or device within 4 weeks of entering study. Have abnormal liver function tests defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times ULN within 28 days prior to informed consent. 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. 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. Have a known hypersensitivity to any constituent of the product. Presence of any condition that the Investigator believes would put the patient at risk.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Omeros Clinical Trial Information
Phone
206-676-5000
Email
ctinfo@omeros.com
Facility Information:
Facility Name
Omeros Investigational Site
City
San Diego
State/Province
California
ZIP/Postal Code
92024
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Omeros Investigational Site
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32608
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Omeros Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Omeros Investigational Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Omeros Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Omeros Investigational Site
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Individual Site Status
Recruiting
Facility Name
Omeros Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Omeros Investigational Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Omeros Investigational Site
City
Halle
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Omeros Investigational Site
City
Hanover
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Omeros Investigational Site
City
Budapest
Country
Hungary
Individual Site Status
Not yet recruiting
Facility Name
Omeros Investigational Site
City
Haifa
Country
Israel
Individual Site Status
Not yet recruiting
Facility Name
Omeros Investigational Site
City
Jerusalem
Country
Israel
Individual Site Status
Not yet recruiting
Facility Name
Omeros Investigational Site
City
Ramat Gan
Country
Israel
Individual Site Status
Not yet recruiting
Facility Name
Omeros Investigational Site
City
Tel Aviv
Country
Israel
Individual Site Status
Not yet recruiting
Facility Name
Omeros Investigational Site
City
Utrecht
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Name
Omeros Investigational Site
City
Pamplona
Country
Spain
Individual Site Status
Not yet recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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

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