A Study of Pegcetacoplan for Patients With Transplant-associated Thrombotic Microangiopathy After Hematopoietic Stem Cell Transplantation

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)

The purpose of the study was to assess pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of pegcetacoplan in patients with TA-TMA after HSCT.

This was a pilot study, and the sample size was based on practical rather than statistical aspects.

A total of 12 patients were to be included and treated in the study. With 12 patients included, it was estimated that 9 patients would complete at least 4 weeks of treatment, which is deemed sufficient to characterize the PK of pegcetacoplan in patients with TA-TMA to an appropriate precision. In addition, 12 patients would provide a 72 % probability to observe a response rate of at least 8 responders of the 12 patients recruited (assuming the true response rate is 70 %).

Inclusion Criteria:

1. Male and female patients aged ≥ 18 years at the time of informed consent form (ICF) signature.

2. Received allogeneic HSCT.

3. Diagnosis of TA-TMA established, as per laboratory markers indicating TMA.

4. Have a diagnosis of TA-TMA that persists despite initial management of any triggering condition.

5. Have random urine protein/creatinine ratio (rUPCR) ≥ 1 mg/mg.

6. 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 investigational medicinal product (IMP) dose.

   Note: Postmenopausal is defined as having had 12 consecutive months with no menses without an alternative medical cause.

7. Men must agree to the following for the duration of the study and 8 weeks after their last dose of IMP:

   1. Avoid fathering a child.
   2. Use protocol-defined methods of contraception.
   3. Refrain from donating sperm.

8. 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:

1. Positive direct Coombs test.
2. Known familial or acquired ADAMTS13 deficiency.
3. Known Shiga toxin-related hemolytic uremic syndrome.
4. Known bone marrow or graft failure.
5. Diagnosis of disseminated intravascular coagulation.
6. Diagnosis of veno-occlusive disease (VOD).
7. Active GI bleeding (hematemesis or hematochezia) at baseline.
8. Body weight < 30 kg and > 100 kg.
9. Uncontrolled systemic bacterial or fungal infection, presence or suspicion of sepsis.
10. Previously or currently treated with a complement inhibitor (approved or investigational).
11. Pregnancy or breastfeeding.
12. Positive human immunodeficiency virus antibody at screening or documented in pre-HSCT medical record.
13. Hepatitis C virus detectable by polymerase chain reaction at screening or documented in pre-HSCT medical record.
14. 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.
15. Known or suspected hereditary fructose intolerance.
16. Hypersensitivity to pegcetacoplan or any of its excipients.
17. 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.