Clinical trial NCT06154512: A Real-world, Multi-center, Prospective, Observational Study for PNH in China
Official title: A Real-world, Multi-center, Prospective, Observational Study for Paroxysmal Nocturnal Haemoglobinuria (PNH) in China
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Keywords: PNH
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-12-04
Enrollment: 724
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study Population:

Number of patients (estimate): 1000; 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.

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Hemolysis：Concentration of LDH changes at each visit from base-line, of all patients
timeFrame: 12 months
measure: Number and percentage of patients with thrombosis within follow-up
timeFrame: 12 months
measure: average number of units of packed RBCs transfused per month, of all patients
timeFrame: 12 months
measure: Number and percentage of patients with renal failure within follow-up
timeFrame: 12 months
measure: Number and percentage of patients with pulmonary hypertension within follow-up
timeFrame: 12 months
Secondary outcomes:
measure: Number and percentage of patients with each symptom of interest within follow-up
timeFrame: 12 months
measure: Demographics at baseline of all patients
timeFrame: baseline
measure: 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
timeFrame: 12 months
measure: All serious adverse events (SAEs)of PNH among eculizumab-treated patients
timeFrame: 12 months
measure: Standard descriptive statistics of pregnancy status
timeFrame: 12 months
measure: Standard descriptive statistics of lactation status
timeFrame: 12 months
measure: Standard descriptive statistics of PNH classification
timeFrame: 12 months
measure: Standard descriptive statistics of flow cytometry results
timeFrame: 12 months
Other outcomes:
measure: Concentration of LDH changes at each visit from base-line of PNH among eculizumab-treated patients
timeFrame: 12 months
measure: Number and percentage of patients with thrombosis within follow up among eculizumab-treated patients
timeFrame: 12 months
measure: average number of units of packed RBCs transfused per month within 12 months v
timeFrame: 12 months
measure: Number and percentage of patients with renal failure within follow up among eculizumab-treated patients
timeFrame: 12 months
measure: Number and percentage of patients with pulmonary hypertension (PH) within follow up among eculizumab-treated patients
timeFrame: 12 months
Locations:
city: Hefei
country: China
facility: Research Site
state: Anhui
city: Beijing
country: China
facility: Research Site
state: Beijing
city: Beijing
country: China
facility: Research Site
state: Beijing
city: Guangzhou
country: China
facility: Research Site
state: Guangdong
city: Guangzhou
country: China
facility: Research Site
state: Guangdong
city: Guangzhou
country: China
facility: Research Site
state: Guangdong
city: Nanning
country: China
facility: Research Site
state: Guangxi
city: Guiyang
country: China
facility: Research Site
state: Guizhou
city: Shijiazhuang
country: China
facility: Research Site
state: Hebei
city: Harbin
country: China
facility: Research Site
state: Heilongjiang
city: Zhengzhou
country: China
facility: Research Site
state: Henan
city: Zhengzhou
country: China
facility: Research Site
state: Henan
city: Zhengzhou
country: China
facility: Research Site
state: Henan
city: Wuhan
country: China
facility: Research Site
state: Hubei
city: Wuhan
country: China
facility: Research Site
state: Hubei
city: Changsha
country: China
facility: Research Site
state: Hunan
city: Changsha
country: China
facility: Research Site
state: Hunan
city: Nanjing
country: China
facility: Research Site
state: Jiangsu
city: Nantong
country: China
facility: Research Site
state: Jiangsu
city: Xuzhou
country: China
facility: Research Site
state: Jiangsu
city: Nanchang
country: China
facility: Research Site
state: Jiangxi
city: Nanchang
country: China
facility: Research Site
state: Jiangxi
city: Changchun
country: China
facility: Research Site
state: Jilin
city: Shenyang
country: China
facility: Research Site
state: Liaoning
city: Jinan
country: China
facility: Research Site
state: Shandong
city: Qingdao
country: China
facility: Research Site
state: Shandong
city: Zibo
country: China
facility: Research Site
state: Shandong
city: Linyi
country: China
facility: Research Site
state: Shangdong
city: Shanghai
country: China
facility: Research Site
state: Shanghai
city: Shanghai
country: China
facility: Research Site
state: Shanghai
city: Taiyuan
country: China
facility: Research Site
state: Shanxi
city: XI 'an
country: China
facility: Research Site
state: Shanxi
city: Xi'an
country: China
facility: Research Site
state: Shanxi
city: Chengdu
country: China
facility: Research Site
state: Sichuan
city: Chengdu
country: China
facility: Research Site
state: Sichuan
city: Tianjin
country: China
facility: Research Site
state: Tianjin
city: Tianjin
country: China
facility: Research Site
state: Tianjin
city: Tianjin
country: China
facility: Research Site
state: Tianjin
city: Kunming
country: China
facility: Research Site
state: Yunnan
city: Hangzhou
country: China
facility: Research Site
Study officials:
References: