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)

• ClinicalTrials.gov Identifier: NCT05148299
• Recruitment Status: Recruiting
• First Posted: December 8, 2021
• Last Update Posted: May 1, 2023
• Sponsor: Swedish Orphan Biovitrum
• Collaborator: Apellis Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Swedish Orphan Biovitrum

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Transplant-Associated Thrombotic Microangiopathy	Drug: Pegcetacoplan	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: open label, single arm, multicenter
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: February 1, 2022
• Estimated Primary Completion Date: March 31, 2024
• Estimated Study Completion Date: March 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pegcetacoplan	Drug: Pegcetacoplan; 20-cc glass vials-1080 mg

Outcome Measures

Primary Outcome Measures :

1. Pegcetacoplan PK parameter AUC0-tau [ Time Frame: Week 24 ]
   Area under the concentration-time curve over the dosing interval
2. Pegcetacoplan PK parameter Cmax [ Time Frame: Week 24 ]
   Maximum observed serum concentration
3. Pegcetacoplan PK parameter Tmax [ Time Frame: Week 24 ]
   Time of maximum measured serum concentration
4. Pegcetacoplan PK parameter Ctrough [ Time Frame: Week 24 ]
   Observed serum concentration predose

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Number of participants with treatment-related adverse events. [ Time Frame: From treatment start to end of study, an average of 6 months ]
   Occurrence and severity of treatment-emergent adverse events.
2. Number of participants with clinically significant changes in vital signs. [ Time Frame: Week 24 ]
   Occurrence of clinically significant changes in vital signs.
3. Number of participants with clinically significant changes in abnormal electrocardiogram findings. [ Time Frame: Week 24 ]
   Occurrence of clinically significant abnormal electrocardiogram findings.
4. Number of participants with antibodies to polyethylene glycol (PEG) and pegcetacoplan throughout treatment and follow-up periods. [ Time Frame: from treatment start to the end of the study, an average of 6 months. ]
   Presence of antibodies to polyethylene glycol (PEG) and pegcetacoplan throughout treatment and follow-up periods.

Eligibility Criteria

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

Criteria

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 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 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.

Contacts and Locations

Contacts

Contact: Luis Lopez Lazaro, MD; 0041 79 834 17 78; Luis.LopezLazaro@sobi.com

Locations

United States, California

Ryotaro Nakamura, MD; Recruiting

Duarte, California, United States, 91010

United States, Minnesota

Hassan AlKhateeb, MD; Recruiting

Rochester, Minnesota, United States, 55905

France

Michael Loschi, MD; Recruiting

Nice, France, 06202

Flore Sicre de Fontbrune, MD; Recruiting

Paris, France, 75010

Jerome Cornillon, MD; Recruiting

Saint-Priest-en-Jarez, France, 42270

Greece

Panagiotis Tsirigotis, MD; Recruiting

Athens, Chaidari, Greece, 12462

Ioannis Baltadakis, MD; Recruiting

Athens, Greece, 10676

Ioanna Sakellari, MD; Recruiting

Thessaloníki, Greece, 57010

Italy

Antonio Risitano, MD; Recruiting

Avellino, Italy, 83100

Giovanni Grillo, MD; Not yet recruiting

Milan, Italy, 20162

Elisabetta Terruzi, MD; Recruiting

Monza, Italy, 20900

Luca Castagna, MD; Recruiting

Palermo, Italy, 900146

Simona Sica, MD; Recruiting

Roma, Italy, 00168

Spain

Rafael Francisco Duarte Palomino, MD; Recruiting

Madrid, Spain, 28222

Sponsors and Collaborators

Swedish Orphan Biovitrum

Apellis Pharmaceuticals, Inc.

More Information

• Responsible Party: Swedish Orphan Biovitrum
• ClinicalTrials.gov Identifier: NCT05148299
• Other Study ID Numbers: Sobi.PEGCET-201
• First Posted: December 8, 2021
• Last Update Posted: May 1, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Swedish Orphan Biovitrum:

TA-TMA

Additional relevant MeSH terms:

Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Hematologic Diseases