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 %).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
20-cc glass vials-1080 mg
City of Hope
Duarte, California, United States
Mayo Clinic - Rochester
Rochester, Minnesota, United States
Saint-Louis Hospital
Paris, Paris, France
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Week 1 up to Week 14
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
Time frame: 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
Time frame: Week 24
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Archet 1 hospital, Department of Clinical Hematology
Nice, France
CHU de Saint-Etienne
Saint-Priest-en-Jarez, France
University General Hospital "Attikon"
Athens, Chaidari, Greece
General Hospital of Athens "Evangelismos"
Athens, Greece
General Hospital of Thessaloniki "G. Papanikolaou", Hematology Department - BMT Unit
Thessaloniki, Greece
Hospital San Giuseppe Moscati
Avellino, Italy
Big Metropolitan Hospital Niguarda Regional Health Authority
Milan, Italy
...and 4 more locations
Absolute Levels and Change From Baseline in C3
Absolute levels and change from baseline to Week 24 in biomarker of complement activation C3
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Week 24
Overall Survival at Day 100
Survival
Time frame: Day 100 from diagnosis
Overall Survival at Week 24
Survival
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Week 24
Number of Participants Reaching Clinical Response at Week 12
Number of participants reaching clinical response at week 12
Time frame: Week 12
Number of Participants Reaching TMA Response at Week 12
Number of participants reaching TMA response at week 12
Time frame: Week 12