A Study to Evaluate the Pharmacokinetics (PK), Efficacy and Safety and Tolerability of Pegcetacoplan in Patients With TA-TMA After Hematopoietic Stem Cell Transplantation (HSCT)

Study Overview
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Brief Summary
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The purpose of the study is to assess PK, Pharmacodynamics (PD), Efficacy and safety of pegcetacoplan in patients with TA-TMA after HSCT.

Official Title
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An Open-label, Single-arm, Multicenter Pilot Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Efficacy and Safety of Pegcetacoplan in Patients With Transplant-associated Thrombotic Microangiopathy (TA-TMA) After Hematopoietic Stem Cell Transplantation (HSCT)

Conditions
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Transplant-Associated Thrombotic Microangiopathy

Intervention / Treatment
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* Drug: Pegcetacoplan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients aged ≥ 18 years at the time of informed consent form (ICF) signature. Received allogeneic HSCT. Diagnosis of TA-TMA established, as per laboratory markers indicating TMA. Have a diagnosis of TA-TMA that persists despite initial management of any triggering condition. Have rUPCR ≥ 1 mg/mg. Women of childbearing potential, defined as any women who have experienced menarche and who are NOT permanently sterile or postmenopausal, must have a negative serum pregnancy test at screening and agree to use protocol-defined methods of contraception for the duration of the study and 8 weeks after their last IMP dose. Note: Postmenopausal is defined as having had 12 consecutive months with no menses without an alternative medical cause. Men must agree to the following for the duration of the study and 8 weeks after their last dose of IMP: Avoid fathering a child. Use protocol-defined methods of contraception. Refrain from donating sperm. Patient and/or legally authorized representative must be capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF. Exclusion Criteria: Positive direct Coombs test. Known familial or acquired ADAMTS13 deficiency. Known Shiga toxin-related hemolytic uremic syndrome. Known bone marrow or graft failure. Diagnosis of disseminated intravascular coagulation. Diagnosis of veno-occlusive disease (VOD). Active GI bleeding (hematemesis or hematochezia) at baseline. Body weight < 30 kg and > 100 kg. Uncontrolled systemic bacterial or fungal infection, presence or suspicion of sepsis. Previously or currently treated with a complement inhibitor (approved or investigational). Pregnancy or breastfeeding. Positive human immunodeficiency virus antibody at screening or documented in pre-HSCT medical record. Hepatitis C virus detectable by polymerase chain reaction at screening or documented in pre-HSCT medical record. Chronic inactive hepatitis B virus with viral loads > 1000 IU/mL (> 5000 copies/mL) at screening or documented in pre-HSCT medical record. Eligible patients who are chronic active carriers (≤ 1000 IU/mL) must receive prophylactic antiviral treatment (e.g., entecavir, tenofovir, lamivudine) according to local country guidelines. Known or suspected hereditary fructose intolerance. Hypersensitivity to pegcetacoplan or any of its excipients. Inability to cooperate with study procedures or any condition that, in the opinion of the investigator, could increase the patient's risk by participating in the study or confound the outcome of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: open label, single arm, multicenter
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pegcetacoplan<br> | Drug: Pegcetacoplan<br>* 20-cc glass vials-1080 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pegcetacoplan PK parameter AUC0-tau | Area under the concentration-time curve over the dosing interval | Week 24 | 
| Pegcetacoplan PK parameter Cmax | Maximum observed serum concentration | Week 24 | 
| Pegcetacoplan PK parameter Tmax | Time of maximum measured serum concentration | Week 24 | 
| Pegcetacoplan PK parameter Ctrough | Observed serum concentration predose | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute levels, change from baseline, and percent change in sC5b-9 | Absolute levels, change from baseline, and percent change from baseline to Week 24 in biomarker of complement activation sC5b-9 | Week 24 | 
| Number of participants reaching clinical response at week 24 | A participant will be declared as reaching a clinical response upon improvement in laboratory markers of TMA and resolution of TMA clinical symptoms | Week 24 | 
| Number of participants reaching TMA response at week 24 | A participant will be declared as reaching TMA response upon improvement in laboratory markers of TMA | Week 24 | 
| Overall survival | Survival | Day 100 from diagnosis | 
| Overall survival | Survival | Week 24 from treatment start | 
| Time to clinical response. | Both clinical response sustained at week 24 and clinical response at any time during the study will be assessed. | From treatment start to first documentation of attainment of a clinical response | 
| Time to TMA response. | Both TMA response sustained at week 24 and TMA response at any time during the study will be assessed. | From treatment start to first documentation of attainment of a TMA response | 
| Duration of clinical response. |  | From the first observed clinical response until the response criteria is no longer fulfilled or until end of study | 
| Duration of TMA response. |  | From the first observed TMA response until the response criteria is no longer fulfilled or until end of study | 
| TA-TMA relapse at Week 24. | A participant will be declared as relapsing upon appearance of laboratory markers of TMA | Week 24 | 
| Number of participants reaching clinical response at week 12 |  | Week 12 | 
| Number of participants reaching TMA response at week 12 |  | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TA-TMA