Eculizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) in China

Study Overview
=================
Brief Summary
-----------------
This is a Phase 3b, single-arm, open-label, multicenter study to evaluate the efficacy, safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of eculizumab in adult participants with paraxysmal noturnal hemoglobinuria (PNH) in China.

Detailed Description
-----------------
This is a Phase 3b, single-arm, open-label, multicenter study to evaluate the efficacy, safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of eculizumab in adult participants with PNH in China who previously have not been treated with complement inhibitors. Approximately 25 eligible participants in China will be enrolled.

Official Title
-----------------
Open-Label, Multicenter Study to Assess the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Eculizumab in Complement Inhibitor Treatment Naïve Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) in China

Conditions
-----------------
Paroxysmal Nocturnal Hemoglobinuria

Intervention / Treatment
-----------------
* Drug: Eculizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult C5 inhibitor naïve PNH patients (age>=18), which is confirmed by flow cytometry evaluation. Must be vaccinated against N meningitidis. Exclusion Criteria: Meningitidis infection or unresolved meningococcal disease Significant bone marrow failure Other significant systemic diseases that might have impact on efficacy and safety assessment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: open label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eculizumab<br>Eculizumab will be administered by IV infusion. | Drug: Eculizumab<br>* Participants will receive 600 milligrams (mg) once a week on Day 1, 8, 15, and 22 followed by 900 mg every 2 weeks from Day 29 to Day 435.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change from baseline in Lactate Dehydrogenase (LDH) at Week 12 | To assess efficacy of eculizumab in participants with PNH | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number(%) of participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | To assess the safety and tolerability of eculizumab in participants with PNH | Baseline through Week 64 | 
| Pharmacokinetics (PK): Serum Eculizumab Concentration | To characterize the pharmacokinetics of eculizumab in participants with PNH | Baseline through Week 64 (predose and postdose) | 
| Change from baseline in Serum Free and total Complement 5 (C5) Concentration | To characterize the pharmacodynamics of eculizumab in participants with PNH | Baseline through week 64 (predose and postdose) | 
| Number(%) of participants with Antidrug Antibodies (ADAs) to Eculizumab | To characterize the immunogenicity of eculizumab in participants with PNH | Baseline through Week 64 | 
| Change from baseline in functional assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 64 | To assess the efficacy of eculizumab in participants with PNH | Baseline through Week 64 | 
| Number(%) of participants with Breakthrough Hemolysis | To assess the efficacy of eculizumab in participants with PNH | Baseline through Week 64 | 
| Number(%) of participants achieving LDH Normalization | To assess the efficacy of eculizumab in participants with PNH | Baseline through Week 64 | 
| Number(%) of participants needing Blood Transfusion | To assess the efficacy of eculizumab in participants with PNH | Baseline through Week 64 | 
| Number(%) of participants changes from baseline in vital signs and laboratory parameters at all scheduled visits. | To characterize the safety profile of eculizumab in participants with PNH | Baseline through Week 64 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
paroxysmal nocturnal hemoglobinuria, PNH