Clinical trial NCT05148299: Evaluate the PK Efficacy Safety and Tolerability of Pegcetacoplan in Patients With Thrombotic Microangiopathy
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Transplant-Associated Thrombotic Microangiopathy
Keywords: TA-TMA
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
Collaborators: name: Apellis Pharmaceuticals, Inc.
First posted: 2021-12-08
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: open label, single arm, multicenter
Primary purpose: TREATMENT

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.

Detailed description: This is a pilot study and the sample size is based on practical rather than statistical aspects.

A total of 12 patients will be included and treated in the study. With 12 patients included, it is estimated that 9 patients will 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 will provide a 72 % probability to observe a response rate of at least 8 responders of the 12 patients recruited (assuming the true response rates is 70 %).

Eligibility 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.

Primary outcomes:
measure: Pegcetacoplan PK parameter AUC0-tau
timeFrame: Week 24
measure: Pegcetacoplan PK parameter Cmax
timeFrame: Week 24
measure: Pegcetacoplan PK parameter Tmax
timeFrame: Week 24
measure: Pegcetacoplan PK parameter Ctrough
timeFrame: Week 24
Secondary outcomes:
measure: Absolute levels, change from baseline, and percent change in sC5b-9
timeFrame: Week 24
measure: Number of participants reaching clinical response at week 24
timeFrame: Week 24
measure: Number of participants reaching TMA response at week 24
timeFrame: Week 24
measure: Overall survival
timeFrame: Day 100 from diagnosis
measure: Overall survival
timeFrame: Week 24 from treatment start
measure: Time to clinical response.
timeFrame: From treatment start to first documentation of attainment of a clinical response
measure: Time to TMA response.
timeFrame: From treatment start to first documentation of attainment of a TMA response
measure: Duration of clinical response.
timeFrame: From the first observed clinical response until the response criteria is no longer fulfilled or until end of study
measure: Duration of TMA response.
timeFrame: From the first observed TMA response until the response criteria is no longer fulfilled or until end of study
measure: TA-TMA relapse at Week 24.
timeFrame: Week 24
measure: Number of participants reaching clinical response at week 12
timeFrame: Week 12
measure: Number of participants reaching TMA response at week 12
timeFrame: Week 12
Other outcomes:
measure: Number of participants with treatment-related adverse events.
timeFrame: From treatment start to end of study, an average of 6 months
measure: Number of participants with clinically significant changes in vital signs.
timeFrame: Week 24
measure: Number of participants with clinically significant changes in abnormal electrocardiogram findings.
timeFrame: Week 24
measure: Number of participants with antibodies to polyethylene glycol (PEG) and pegcetacoplan throughout treatment and follow-up periods.
timeFrame: from treatment start to the end of the study, an average of 6 months.
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Nice
country: France
facility: Archet 1 hospital, Department of Clinical Hematology
city: Paris
country: France
facility: Saint-Louis Hospital
city: Saint-Priest-en-Jarez
country: France
facility: CHU de Saint-Etienne
city: Athens
country: Greece
facility: University General Hospital "Attikon"
state: Chaidari
city: Athens
country: Greece
facility: General Hospital of Athens "Evangelismos"
city: Thessaloníki
country: Greece
facility: General Hospital of Thessaloniki "G. Papanikolaou", Hematology Department - BMT Unit
city: Avellino
country: Italy
facility: Hospital San Giuseppe Moscati
city: Milan
country: Italy
facility: Big Metropolitan Hospital Niguarda Regional Health Authority
city: Monza
country: Italy
facility: ASST Monza - S. Gerardo Hospital
city: Palermo
country: Italy
facility: United Hospitals Villa Sofia Cervello
city: Roma
country: Italy
facility: University Polyclinic Foundation "Agostino Gemelli" - IRCCS
city: Madrid
country: Spain
facility: University Hospital Puerta de Hierro Majadahonda
Study officials:
affiliation: Swedish Orphan Biovitrum AB
name: Study physician
role: STUDY_DIRECTOR
References: