A Phase 2 Study on Narsoplimab in Paediatric Patients with High Risk Haematopoietic Stem Cell Transplant Thrombotic Microangiopathy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Omeros Corp.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

11 Jul 2023 → ongoing

Decision date (initial)

2024-06-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Omeros Corporation

External identifiers

EU CT number

2023-509710-11-00

EudraCT number

2021-002727-38

ClinicalTrials.gov

NCT05855083

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Pharmacokinetic, Efficacy

Describe the 100-day survival rate following high-risk HSCT-TMA diagnosis.

Secondary objectives 5

1. Evaluate the safety and tolerability of intravenous (IV) administration of narsoplimab.
2. Describe the efficacy of narsoplimab by responder rate; survival at 52 weeks; and mean, median, and overall survival rates.
3. Evaluate peak and trough PK of IV narsoplimab.
4. Immunogenicity will be evaluated.
5. Anti-drug antibody (ADA) responses will be summarized by treatment group and will be evaluated.

Conditions and MedDRA coding

Haematopoietic Stem Cell Transplant Thrombotic Microangiopathy

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002479-PIP01-18

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

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 laws and regulations. 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 laws and regulations.
4. Have received an allogeneic HSCT 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: a. Platelet count < 50,000/μL or a decrease in platelet count > 50% from the highest value obtained following transplant or are platelet transfusion dependent b. 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: a. Spot protein/creatinine ratio > 1 mg/mg b. TMA-related serum creatinine > 2 x the creatinine level prior to TMA development (sustained elevation for at least 48 hours) or a 50% decline in the estimated or measured glomerular filtration rate using either serum creatinine or cystatin C c. Biopsy-proven gastrointestinal TMA d. TMA-related neurological abnormality (e.g., confusion, stroke, transient ischemic attack [TIA], or seizures) e. Pericardial or pleural effusion without alternative explanation f. Pulmonary hypertension without alternative explanation g. Concurrent Grade II, III, or IV graft versus host disease (GVHD) h. Concurrent bacterial or viral infection i. Concurrent gastrointestinal bleeding j. Concurrent diffuse alveolar hemorrhage or need for positive-pressure ventilation (noninvasive or invasive) for ≥ 24 hours in the absence of alternative definite etiology k. Have elevated serum C5b-9 (>ULN) l. Peak LDH ≥ 2 x ULN
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 during study treatment and for at least 12 weeks following the last dose of study medication.

Exclusion criteria 12

1. Use of a complement inhibitor (e.g. eculizumab or ravulizumab) within 3 months prior to screening, except: a. Failure of the therapy for the current episode of HSCT-TMA can be documented (including if the patient had completed prior therapy within the period and relapsed subsequently after completing therapy) b. Therapy was for another indication (e.g., paroxysmal nocturnal hemoglobinuria for which patient underwent HSCT) and the HSCT-TMA developed on or after discontinuing the therapy Note - Patients may not be on another complement inhibitor for any indication at the time of first narsoplimab dosing, i.e., prior therapy must have been discontinued.
2. 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.
3. Have a known hypersensitivity to any constituent of the product.
4. Presence of any condition that the Investigator believes would put the patient at risk.
5. Use of defibrotide within 3 months prior to screening, except: a. Therapy was for veno-occlusive disease (VOD) prophylaxis and the HSCT-TMA developed after having started defibrotide therapy. b. Therapy was for VOD treatment, the VOD is stable (not worsened) or improving, and the HSCT-TMA developed after having started defibrotide therapy. Note - Patients on defibrotide for one of the above reasons may remain on defibrotide during the study.
6. Have ADAMTS13 activity < 10%. Test results obtained within 28 days prior to informed consent may be used. Test result may be pending (must have been obtained) at time of first dose if patient requires urgent treatment.
7. 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.
8. 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.
9. If pregnant or lactating
10. Have received treatment with an investigational drug or device within 4 weeks of entering study, except: a. Investigational usage of an approved drug substance or a dietary supplement may be allowable; contact the medical monitor for approval prior to enrollment. b. Other investigational agents, not for the treatment of HSCT-TMA, may be allowable; contact the medical monitor for approval prior to enrollment.
11. Have abnormal liver function tests defined as alanine aminotransferase (ALT) > 10 times ULN at time of informed consent through prior to the first dose.
12. Have a positive test by antigen, antibody, or polymerase chain reaction (PCR) for human immunodeficiency virus (HIV); if previously negative from time of transplant evaluation up to informed consent, the test does not need to be repeated.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 100-day survival rate from date of HSCT-TMA diagnosis

Secondary endpoints 5

1. Survival at 52 weeks and median, mean, and overall survival from date of TMA diagnosis
2. Narsoplimab peak and trough PK and concomitant lectin pathway activation measured by ex vivo assay
3. Safety will be evaluated by adverse events and laboratory measures.
4. Anti-drug antibody response
5. Responder rate based on clinical response criteria

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Omeros Corp.

Sponsor organisation

Omeros Corp.

Address

201 Elliott Avenue West

City

Seattle

Postcode

98119-4240

Country

United States

Scientific contact point

Organisation

Omeros Corp.

Contact name

William Pullman

Public contact point

Organisation

Omeros Corp.

Contact name

Clinical Trial Administrator

Third parties 6

Sponsor responsibilities

Article 77 compliance

Omeros Corp.

Contact point sponsor

Omeros Corp.

Article 77 implementation

Omeros Corp.

Locations

3 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications