A Real-world, Multi-center, Prospective, Observational Study for PNH in China

Paroxysmal Nocturnal Hemoglobinuria Clinical Trial

— ReWoPNH  

Official title:

A Real-world, Multi-center, Prospective, Observational Study for Paroxysmal Nocturnal Haemoglobinuria (PNH) in China

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06154512
• Other study ID #: D7414R00001
• Status: Recruiting
• Start date: November 10, 2023
• Est. completion date: November 30, 2025

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

As a rare disease listed in the First Catalogue of Rare Diseases in China (National Health Commission of the People's Republic of China, 2019), PNH is poorly studied in China subse-quently leading to the inadequate elucidation of disease characteristics and clinical outcomes. Eculizumab was recently approved by NMPA. The availability of Eculizumab in China pro-vides people living with PNH with a new treatment option that can reduce disease symptoms and prevent the dysregulated complement system from causing further damage. A Phase Ⅳ study is necessary to understand the natural history of disease and the clinical outcomes with different medical interventions.

Description:

Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare and life-threatening acquired disorder of the pluripotent hematopoietic stem cell and therefore can affect erythrocytes, leukocytes, thrombocytes and probably some endothelial cells. These hematopoietic stem cells have acquired a somatic mutation in the phosphatidylinositol glycan class A (PIG-A) This gene is required for the synthesis of the glycosyl phosphatidyl-inositol (GPI) anchor, which is necessary to attach some proteins to the blood cell membrane. Therefore, a lack of two important complement regulatory proteins is observed on the cell surface: 'decay-accelerating factor' (DAF), also called 'CD55' and 'membrane inhibitor of reactive lysis' (MIRL), also called 'CD59' Thus, red blood cells are more vulnerable to the attack by the complement activation product MAC (complement membrane attack complex). This leads to a complement-mediated intravascular hemolysis. The predisposition of venous thrombosis, hemolytic anemia, complete thrombocytopenia, and thrombosis are the three main characteristics of the disease. Its incidence is not really known but estimated at 0.1~0.6/100 000 per-sons/yr, and prevalence is estimated at 1~4 cases/100,000 persons/yr. PNH was listed in the First Catalogue of Rare Diseases in China, and its incidence was previously reported to be 1/100,000 persons/year, peak onset age 20~40 years.

PNH can be classified into 3 different forms: classical PNH, PNH associated with aplastic anemia (PNH-AA), and subclinical PNH, based on clinical features, bone marrow characteristics, and the size of the mutant clone. The traditional treatment of PNH is still aimed at "protecting" the PNH clone, reducing complement attack and destruction, and alleviating hemolysis with symptomatic supportive therapy. In acute hemolytic episodes, could be administered adrenal glucocorticoids, complemented by cell membrane stabilizers, folic acid, and alkaline drugs. In case of PNH-AA syndrome, treatment with androgens and immunosuppressants may be used; anticoagulation and heparin therapy should be given for the occurrence of thrombosis; other symptomatic supportive treatments include transfusion of red blood cells and platelets if necessary as well as antibacterial drugs in case of infection. Bone marrow transplantation is the only curative therapy for PNH presupposes, but patient need to achieve complete remission with chemotherapy first and a suitable donor is needed.

Besides supportive care, global guidance/consensus also recommend C5 complement inhibitor Eculizumab as a treatment method, and its use could significantly improve 5-year survival rate to 95.5%. Eculizumabis a humanized, first-in-class, anti-C5 antibody that binds with high affinity to C5 and blocks the terminal complement-C5a and C5b-9 formation, reducing the chronic uncontrolled complement activation and its consequences. Eculizumab has been approved for PNH by National Medical Products Administration in August, 2022.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: November 30, 2025
• Est. primary completion date: November 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria

1. Patients of any age;

2. Diagnosed PNH with detected proportion of PNH clone cells of at least 1%;

3. Patient or patient's family must be willing and able to give written informed consent.

Exclusion Criteria

1. Current or previous treatment with a non-eculizumab complement inhibitor;

2. Patients in other PNH clinical trials.

3. Unable to give written informed consent.

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Paroxysmal Nocturnal Hemoglobinuria

Locations

Country	Name	City	State
China	Research Site	Beijing	Beijing
China	Research Site	Beijing	Beijing
China	Research Site	Changchun	Jilin
China	Research Site	Changsha	Hunan
China	Research site	Changsha	Hunan
China	Research site	Chengdu	Sichuan
China	Research site	Chengdu	Sichuan
China	Research Site	Guangzhou	Guangdong
China	Research Site	Guangzhou	Guangdong
China	Research Site	Guangzhou	Guangdong
China	Research site	Guiyang	Guizhou
China	Research site	Harbin	Heilongjiang
China	Research Site	Hefei	Anhui
China	Research site	Kunming	Yunnan
China	Research Site	Linyi	Shangdong
China	Research site	Nanchang	Jiangxi
China	Research site	Nanchang	Jiangxi
China	Research Site	Nanjing	Jiangsu
China	Research site	Nanning	Guangxi
China	Research Site	Nantong	Jiangsu
China	Research Site	Qingdao	Shandong
China	Research Site	Qingdao	Shandong
China	Research Site	Shanghai	Shanghai
China	Research Site	Shanghai	Shanghai
China	Research Site	Shenyang	Liaoning
China	Research Site	Shijiazhuang	Hebei
China	Research Site	Taiyuan	Shanxi
China	Research Site	Tianjin	Tianjin
China	Research Site	Tianjin	Tianjin
China	Research site	Tianjin	Tianjin
China	Research Site	Wuhan	Hubei
China	Research Site	Wuhan	Hubei
China	Research Site	Xi'an	Shanxi
China	Research site	Xi'an	Shanxi
China	Research site	Xuzhou	Jiangsu
China	Research site	Zhengzhou	Henan
China	Research Site	Zhengzhou	Henan
China	Research site	Zhengzhou	Henan
China	Research site	Zibo	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Concentration of LDH changes at each visit from base-line of PNH among eculizumab-treated patients	Exploratory objective: To characterize the progression of PNH among eculizumab-treated patients	12 months
Other	Number and percentage of patients with thrombosis within follow up among eculizumab-treated patients	Exploratory objective: To characterize the progression of PNH among eculizumab-treated patients	12 months
Other	average number of units of packed RBCs transfused per month within 12 months v	Exploratory objective: To characterize the progression of PNH among eculizumab-treated patients	12 months
Other	Number and percentage of patients with renal failure within follow up among eculizumab-treated patients	Exploratory objective: To characterize the progression of PNH among eculizumab-treated patients	12 months
Other	Number and percentage of patients with pulmonary hypertension (PH) within follow up among eculizumab-treated patients	Exploratory objective: To characterize the progression of PNH among eculizumab-treated patients	12 months
Primary	Hemolysis:Concentration of LDH changes at each visit from base-line, of all patients	To characterize the progression of PNH	12 months
Primary	Number and percentage of patients with thrombosis within follow-up	To characterize the progression of PNH	12 months
Primary	average number of units of packed RBCs transfused per month, of all patients	To characterize the progression of PNH	12 months
Primary	Number and percentage of patients with renal failure within follow-up	To characterize the progression of PNH	12 months
Primary	Number and percentage of patients with pulmonary hypertension within follow-up	To characterize the progression of PNH	12 months
Secondary	Number and percentage of patients with each symptom of interest within follow-up	To describe clinical characteristics of patients with PNH in China	12 months
Secondary	Demographics at baseline of all patients	To describe clinical characteristics of patients with PNH in China	baseline
Secondary	Number and percentage of patients receiving each type of treatment method at baseline and each visit within follow up, including glucocorticoid, red blood cell transfusion, other supportive treatment, bone marrow transplant, eculizumab, of all patients	To describe the treatment pattern of PNH in China	12 months
Secondary	All serious adverse events (SAEs)of PNH among eculizumab-treated patients	To describe the safety of Eculizumab treatment via Serious Adverse Events	12 months
Secondary	Standard descriptive statistics of pregnancy status	To describe clinical characteristics of patients with PNH in China	12 months
Secondary	Standard descriptive statistics of lactation status	To describe clinical characteristics of patients with PNH in China	12 months
Secondary	Standard descriptive statistics of PNH classification	To describe clinical characteristics of patients with PNH in China	12 months
Secondary	Standard descriptive statistics of flow cytometry results	To describe clinical characteristics of patients with PNH in China	12 months