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.

Study Overview

• Status: Completed
• Conditions: Transplant-Associated Thrombotic Microangiopathy
• Intervention / Treatment: Drug: Pegcetacoplan

Detailed Description

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 %).

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Nice, France, 06200
    • Archet 1 hospital, Department of Clinical Hematology
  • Saint-Priest-en-Jarez, France, 42270
    • CHU de Saint-Etienne
  • Paris
    • Paris, Paris, France, 75010
      • Saint-Louis Hospital
• Greece
  • Athens, Greece, 10676
    • General Hospital of Athens "Evangelismos"
  • Thessaloniki, Greece, 57010
    • General Hospital of Thessaloniki "G. Papanikolaou", Hematology Department - BMT Unit
  • Chaidari
    • Athens, Chaidari, Greece, 12462
      • University General Hospital "Attikon"
• Italy
  • Avellino, Italy, 83100
    • Hospital San Giuseppe Moscati
  • Milan, Italy, 20162
    • Big Metropolitan Hospital Niguarda Regional Health Authority
  • Monza, Italy, 20900
    • ASST Monza - S. Gerardo Hospital
  • Palermo, Italy, 90146
    • United Hospitals Villa Sofia Cervello
  • Roma, Italy, 00168
    • University Polyclinic Foundation "Agostino Gemelli" - IRCCS
• Spain
  • Madrid, Spain, 28222
    • University Hospital Puerta de Hierro Majadahonda
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pegcetacoplan; sterile solution in stoppered glass vial given as infusion, for a total treatment duration of 12 to 16 weeks.	Drug: Pegcetacoplan; 20-cc glass vials-1080 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pegcetacoplan Pharmacokinetic (PK) Parameter Area Under the Curve Limited to the End of Dosing Interval (AUC0-tau)	Area under the concentration-time curve limited to the end of the dosing interval. The samples included in the calculation of AUC0-tau were collected at the following times: on dosing Days 1, 3 and 5, PK samples were taken up to 30 minutes pre-dose and at 15 minutes (± 5 min), 30 minutes (± 5 min), 1 hour (± 10 min), 4 hours (± 10 min), 8 hours (± 30 min), and 24 hours (± 30 min) post-dose as well as on Day 8 pre-dose.	Week 1
Pegcetacoplan PK Parameter Maximal Serum Concentration (Cmax)	Maximum observed serum concentration. Determined using the samples collected post-dose on dosing Days 1, 3 and 5.	Week 1
Pegcetacoplan PK Parameter Time to Cmax (Tmax)	Time of maximum measured serum concentration. Determined using the samples collected post-dose on dosing Days 1, 3 and 5.	Week 1
Pegcetacoplan PK Parameter Observed Serum Concentration Pre-dose (Ctrough)	Observed serum concentration pre-dose. From Day 8 (Week 1) and onwards, PK samples were taken pre-dose at each visit.	Week 1 up to Week 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Levels and Change From Baseline in sC5b-9	Absolute levels and change from baseline to Week 24 in biomarker of complement activation sC5b-9	Week 24
Absolute Levels and Change From Baseline in C3a	Absolute levels and change from baseline to Week 24 in biomarker of complement activation C3a	Week 24
Absolute Levels and Change From Baseline in C3	Absolute levels and change from baseline to Week 24 in biomarker of complement activation C3	Week 24
Absolute Levels and Change From Baseline in Bb	Absolute levels and change from baseline to Week 24 in biomarker of complement activation Bb	Week 24
Absolute Levels and Change From Baseline in C4a	Absolute levels and change from baseline to Week 24 in biomarker of complement activation C4a	Week 24
Absolute Levels and Change From Baseline in Classical Pathway (CH50)	Absolute levels and change from baseline to Week 24 in biomarker of complement activation CH50	Week 24
Absolute Levels and Change From Baseline in Alternative Pathway (AH50)	Absolute levels and change from baseline to Week 24 in biomarker of complement activation AH50	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 at Day 100	Survival	Day 100 from diagnosis
Overall Survival at Week 24	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, up to 24 weeks
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, up to 24 weeks
Duration of Clinical Response	Duration of clinical response sustained at week 24	From the first observed clinical response until the response criteria is no longer fulfilled or until end of study, up to 24 weeks
Duration of TMA Response	Duration of TMA response sustained at week 24	From the first observed TMA response until the response criteria is no longer fulfilled or until end of study, up to 24 weeks
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	Number of participants reaching clinical response at week 12	Week 12
Number of Participants Reaching TMA Response at Week 12	Number of participants reaching TMA response at week 12	Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events	Occurrence and severity of treatment-emergent adverse events.	From treatment start to end of study, up to 6 months (8 weeks since last dose of IMP)
Change From Baseline in Platelets	Change from baseline to Week 24 in platelets	Week 24
Change From Baseline in Hemoglobin	Change from baseline to Week 24 in hemoglobin	Week 24
Change From Baseline in Lactate Dehydrogenase (LDH)	Change from baseline to Week 24 in LDH	Week 24
Change From Baseline in Haptoglobin	Change from baseline to Week 24 in haptoglobin	Week 24
Change From Baseline in Indirect Bilirubin	Change from baseline to Week 24 in indirect bilirubin	Week 24
Change From Baseline in Serum Creatinine	Change from baseline to Week 24 in serum creatinine	Week 24
Change From Baseline in Urine Protein/Creatinine Ratio	Change from baseline to Week 24 in urine protein/creatinine ratio	Week 24
Change From Baseline in Systolic Blood Pressure	Change from baseline to Week 24 in systolic blood pressure. Post-dose is 30 minutes after stop of infusion. The timepoints from Week 16 onward have a single value as no infusions were administered at these study visits.	Week 24
Change From Baseline in Diastolic Blood Pressure	Change from baseline to Week 24 in diastolic blood pressure. Post-dose is 30 minutes after stop of infusion. The timepoints from Week 16 onward have a single value as no infusions were administered at these study visits.	Week 24
Change From Baseline in Respiratory Rate	Change from baseline to Week 24 in respiratory rate. Post-dose is 30 minutes after stop of infusion. The timepoints from Week 16 onward have a single value as no infusions were administered at these study visits.	Week 24
Change From Baseline in Heart Rate	Change from baseline to Week 24 in heart rate. Post-dose is 30 minutes after stop of infusion. The timepoints from Week 16 onward have a single value as no infusions were administered at these study visits.	Week 24
Change From Baseline in Temperature	Change from baseline to Week 24 in temperature. Post-dose is 30 minutes after stop of infusion. The timepoints from Week 16 onward have a single value as no infusions were administered at these study visits.	Week 24
Number of Participants With Clinically Significant Changes in Abnormal Electrocardiogram Findings	Occurrence of clinically significant abnormal electrocardiogram findings.	Week 24
Number of Participants With Antibodies to Pegcetacoplan Throughout Treatment and Follow-up Periods	Presence of antibodies to pegcetacoplan throughout treatment and follow-up periods.	from treatment start to the end of the study, up to 6 months.
Number of Participants With Antibodies to Polyethylene Glycol (PEG) Throughout Treatment and Follow-up Periods	Presence of antibodies to PEG throughout treatment and follow-up periods. Baseline represents the situation at treatment start.	from treatment start to the end of the study, up to 6 months.
Number of Participants With Treatment-emergent Anti-PEG Antibodies Throughout Treatment and Follow-up Periods	Presence of treatment-emergent anti-PEG antibodies throughout treatment and follow-up periods. Conservatively, the anti-PEG antibodies detected in a patient with a missing baseline sample have been considered as treatment-emergent.	from treatment start to the end of the study, up to 6 months.

Collaborators and Investigators

• Sponsor: Swedish Orphan Biovitrum
• Collaborators: Apellis Pharmaceuticals, Inc.
• Investigators: Study Director: Study Physician, Swedish Orphan Biovitrum AB

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Actual): December 8, 2024
• Study Completion (Actual): December 8, 2024

Study Registration Dates

• First Submitted: October 21, 2021
• First Submitted That Met QC Criteria: November 24, 2021
• First Posted (Actual): December 8, 2021

Study Record Updates

• Last Update Posted (Actual): November 28, 2025
• Last Update Submitted That Met QC Criteria: November 26, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: TA-TMA
• Additional Relevant MeSH Terms: Cytopenia; Cardiovascular Diseases; Hematologic Diseases; Blood Platelet Disorders; Thrombocytopenia; Vascular Diseases; Thrombotic Microangiopathies; pegcetacoplan
• Other Study ID Numbers: Sobi.PEGCET-201; 2023-510443-37-00 (Ctis); 2021-003157-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No