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

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

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.

Study Overview

• Status: Completed
• Conditions: Paroxysmal Nocturnal Hemoglobinuria
• Intervention / Treatment: Drug: Eculizumab

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, CN-100730
    • Research Site
  • Hangzhou, China, 310003
    • Research Site
  • Nantong, China, 226001
    • Research Site
  • Shanghai, China, 200040
    • Research Site
  • Tianjin, China, 300020
    • Research Site
  • Tianjin, China, 300050
    • Research Site
  • Wuhan, China, 430022
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eculizumab; Eculizumab will be administered by IV infusion.	Drug: Eculizumab; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline in LDH at Week 12	Blood samples were collected for measurement of serum LDH at specified timepoints. Statistical analysis was performed using a mixed model for repeated measures (MMRM), including the percentage change from baseline of LDH at the scheduled visits from Week 1 to Week 12 as the dependent variable, with the fixed categorical effect of visit, fixed continuous effect of LDH baseline value as covariates, and participant as random effect. Assessed at baseline, 1, 2, 3, 4, 6, 8, 10, and 12 weeks, Week 12 reported. A decrease indicated a reduction in disease activity.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that did not necessarily have to have a causal relationship with the study intervention. A TEAE was any AE that started during or after the first infusion of the study intervention. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.	Baseline through Week 64
Serum Concentration of Eculizumab	Blood samples were collected for measurement of serum concentrations of eculizumab at specified timepoints. No study intervention administered on Day 449. Results reported as micrograms/milliliter (ug/mL).	Day 1, Day 29, Day 85, Day 169, Day 253, Day 337, Day 421, Day 449
Change From Baseline in Serum Free Complement 5 (C5) Concentration	Blood samples were collected for measurement of serum concentration of free C5 at specified timepoints. No study intervention administered on Day 449. A decrease indicated a reduction in disease activity.	Day 1, Day 29, Day 85, Day 169, Day 253, Day 337, Day 421, Day 449
Change From Baseline in Serum Total C5 Concentration	Blood samples were collected for measurement of serum concentration of total C5 at specified timepoints. No study intervention administered on Day 449. A decrease indicated a reduction in disease activity.	Day 1, Day 29, Day 85, Day 169, Day 253, Day 337, Day 421, Day 449
Number of Participants With Treatment-emergent Antidrug Antibodies (ADAs) to Eculizumab	Blood samples were collected for measurement of treatment-emergent ADAs to eculizumab at specified timepoints.	Baseline through Week 64
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 12	The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days. The FACIT-Fatigue scale is a collection of quality of life (QoL) questionnaires pertaining to the management of fatigue symptoms due to a chronic illness. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). Total scores were calculated as the sum from all 13 items and ranged from 0 to 52, with higher scores indicating an increased QoL. Analysis was performed using a MMRM, including FACIT-Fatigue score change from baseline values at the scheduled visits from Week 1 to Week 12 as the dependent variable, with the fixed categorical effect of study visit, fixed continuous effect of baseline value of FACIT-Fatigue, and participant as random effect. Assessed at baseline, 1, 2, 3, 4, 6, 8, 10, and 12 weeks, Week 12 reported.	Baseline, Week 12
Percentage of Participants With Breakthrough Hemolysis	Breakthrough hemolysis was defined as at least 1 new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 grams/deciliter], major adverse vascular event [including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2 times (*) upper limit of normal (ULN), after prior LDH reduction to <1.5* ULN on therapy.	Baseline through Week 12
Percentage of Participants Achieving LDH Normalization	Blood samples were collected for measurement of LDH at specified timepoints. LDH normalization was defined as LDH ≤ULN.	Baseline through Week 12
Percentage of Participants Achieving Transfusion Avoidance	Transfusion avoidance was defined as remaining transfusion free (that is, had not received any transfusion) and did not require transfusion as per protocol.	Baseline through Week 12
Percentage of Participants With LDH ≤1.5* ULN at Week 12	Blood samples were collected for measurement of LDH at specified timepoints.	Baseline through Week 12

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.
• Collaborators: AstraZeneca

Publications and helpful links

Helpful Links

• Redacted CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2023
• Primary Completion (Actual): April 14, 2025
• Study Completion (Actual): April 14, 2025

Study Registration Dates

• First Submitted: May 24, 2023
• First Submitted That Met QC Criteria: May 24, 2023
• First Posted (Actual): June 2, 2023

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: PNH; paroxysmal nocturnal hemoglobinuria
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Anemia, Hemolytic; Anemia; Myelodysplastic Syndromes; Hemic and Lymphatic Diseases; Hemoglobinuria, Paroxysmal; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Complement Inactivating Agents; eculizumab
• Other Study ID Numbers: D7414C00001; ECU-PNH-301 (Other Identifier: Alexion)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No