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)

Conditions

Transplant-associated Thrombotic Microangiopathy (TA TMA)

Brief summary

Pegcetacoplan PK parameters: AUC0-tau, Cmax, Tmax and Ctrough.

Detailed description

PD endpoints: o Absolute levels, change from baseline, and % change from baseline to Week 24 in biomarkers of complement activation: sC5b-9, C3a, C3, Bb, C4a, functional assays for classical and alternative complement pathways., Clinical response at Week 24, defined as improvement in laboratory markers and in clinical status (renal, pulmonary, GI, Neurological responses, freedom from transfusion, cardiovascular and serositis responses). Patients meeting intercurrent events, including use of prohibited medication or study withdrawal before Week 24, will be considered as failures/nonresponders., TMA response at Week 24, defined as improvement in laboratory markers as follows: o LDH < 1.5 x ULN and o Platelet count ≥ 50 000/mm3 without transfusion support during the prior 7 days and o ≥ 50 % reduction from baseline in rUPCR., Overall survival at Day 100 from date of TA-TMA diagnosis., Overall survival at Week 24 from treatment start., Time to clinical response., Time to TMA response., Duration of clinical response., Duration of TMA response, TA-TMA relapse at Week 24., Clinical response at Week 12., TMA response at Week 12.

Related papers

No related papers found yet.

Interventions

None listed

Eligibility

Sex/Gender

All

Age

18 Years to No maximum

Design outcomes

Primary

Measure	Time frame
Pegcetacoplan PK parameters: AUC0-tau, Cmax, Tmax and Ctrough.	—

Secondary

Measure	Time frame
PD endpoints: o Absolute levels, change from baseline, and % change from baseline to Week 24 in biomarkers of complement activation: sC5b-9, C3a, C3, Bb, C4a, functional assays for classical and alternative complement pathways., Clinical response at Week 24, defined as improvement in laboratory markers and in clinical status (renal, pulmonary, GI, Neurological responses, freedom from transfusion, cardiovascular and serositis responses). Patients meeting intercurrent events, including use of prohibited medication or study withdrawal before Week 24, will be considered as failures/nonresponders., TMA response at Week 24, defined as improvement in laboratory markers as follows: o LDH < 1.5 x ULN and o Platelet count ≥ 50 000/mm3 without transfusion support during the prior 7 days and o ≥ 50 % reduction from baseline in rUPCR., Overall survival at Day 100 from date of TA-TMA diagnosis., Overall survival at Week 24 from treatment start., Time to clinical response., Time to TMA response.	—

Measure

Time frame

PD endpoints: o Absolute levels, change from baseline, and % change from baseline to Week 24 in biomarkers of complement activation: sC5b-9, C3a, C3, Bb, C4a, functional assays for classical and alternative complement pathways., Clinical response at Week 24, defined as improvement in laboratory markers and in clinical status (renal, pulmonary, GI, Neurological responses, freedom from transfusion, cardiovascular and serositis responses). Patients meeting intercurrent events, including use of prohibited medication or study withdrawal before Week 24, will be considered as failures/nonresponders., TMA response at Week 24, defined as improvement in laboratory markers as follows: o LDH < 1.5 x ULN and o Platelet count ≥ 50 000/mm3 without transfusion support during the prior 7 days and o ≥ 50 % reduction from baseline in rUPCR., Overall survival at Day 100 from date of TA-TMA diagnosis., Overall survival at Week 24 from treatment start., Time to clinical response., Time to TMA response.

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Countries

France, Greece, Italy, Spain

Outcome results