This study will enroll participants aged 12 years or older with a body weight ≥ 40 kilograms (kg) diagnosed with PNH who have not been previously treated with complement inhibitor therapy. Approximately 50 participants will be treated with Crovalimab for at least 24 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
51
Crovalimab will be administered at a dose of 1000 milligrams (mg) IV (for participants with body weight between 40 and 100 kg) or 1500 mg IV (for participants with body weight ≥ 100 kg) on Week 1 Day 1. On Week 1 Day 2 and on Weeks 2, 3 and 4, it will be administered at a dose of 340 mg SC. For Week 5 and Q4W thereafter, it will be administered at a dose of 680 mg SC (for participants with body weight between 40 and 100 kg) or 1020 mg SC (for participants with body weight ≥ 100 kg). Dosing schedule will be as described above.
West China Hospital, Sichuan University
Chengdu, China
Institute of Hematology and Hospital of Blood Disease
Tianjin, China
Tianjin Medical University General Hospital
Tianjin, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology
Wuhan, China
Mean Percentage of Participants With Hemolysis Control
A Generalized Estimating Equation (GEE) was used to estimate the population-average percentage of the participants with hemolysis control (measured by lactate dehydrogenase (LDH) ≤1.5 x upper limit of normal (ULN)) from Week 5 to Week 25 taking account of the intra-patient and inter-patient correlation between LDH control statuses across visits. The dependent variable was the binary indicator for hemolysis control. Independent variables are categorical effects of visits, continuous baseline LDH.
Time frame: From Week 5 up to Week 25
Difference in Percentage of Participants With Transfusion Avoidance (TA) From Baseline Through Week 25 and Within 24 Weeks Prior to Screening
TA was defined as participants who were packed red blood cell (pRBC) transfusion-free and did not require transfusion per protocol-specified guidelines. TA within 24 weeks prior to screening was based on the pRBC transfusion history in the medical records. Reported in this outcome measure is the difference in the percentage of participants between "baseline through Week 25" and "within 24 weeks prior to screening". 95% Confidence Interval (CI) for the difference between the percentage of participants with transfusion avoidance between Pre-screening and Post-baseline is calculated using the Newcombe method. Screening= Day -28 to Day -1 and Baseline= Day 1.
Time frame: 24 Weeks Prior to Screening, Baseline to Week 25
Percentage of Participants With Breakthrough Hemolysis (BTH)
BTH was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath \[dyspnea\], anemia \[hemoglobin \< 10 grams per deciliter (g/dL)\], major adverse vascular event \[MAVE, including thrombosis\], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2xULN after a prior LDH reduction to ≤1.5xULN from the start of study treatment. As pre-specified in the SAP participants withdrawing before Week 25 were deemed to have experienced a BTH event. Percentages have been rounded off to the first decimal point.
Time frame: Baseline, Week 25
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Percentage of Participants With Stabilized Hemoglobin
Stabilized hemoglobin was defined as avoidance of a ≥2 g/dL decrease in hemoglobin level from baseline, in the absence of transfusion. As pre-specified in the SAP participants withdrawing before Week 25 were deemed to not have hemoglobin stabilization.
Time frame: Baseline, Week 25
Change From Baseline in Fatigue in Adults Aged >=18 Years
Fatigue was assessed using functional assessment of chronic illness therapy-fatigue (FACIT-F) scale. FACIT-F is a self-assessment questionnaire with a 7-day recall period and 13 items evaluating fatigue and its impact on daily life activities. Items are scored on a response scale that ranges from 0 ("not at all") to 4 ("very much so"). Relevant items are reverse scored, and all the items are summed to create a total score range from 0 to 52, with 0 being the worst possible score and 52 being the best possible score. A higher score indicates low fatigue severity. A positive mean change indicates improvement. FACIT-F was assessed in adult participants only. FACIT-F assessment was unintentionally missed in the Schedule of Activities (SoA) table, which site used to guide the assessments at each timepoint. Therefore, data were not collected at Week 25.
Time frame: Baseline, Week 2, Week 5, Week 9, Week 17, Week 25
Percentage of Participants With Adverse Events (AEs)
Time frame: Up to 7 years
Percentage of Participants With Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity, and Infections (Including Meningococcal Meningitis)
Time frame: Up to 7 years
Percentage of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation
Time frame: Up to 7 years
Trough Serum Concentration of Crovalimab Over Time
Time frame: Up to 7 years
Serum Concentrations of Crovalimab
Time frame: Up to 7 years
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Crovalimab
Time frame: Up to 7 years
Terminal Complement Activity as Measured by Liposome Immunoassay (LIA)
Time frame: Up to 7 years
Change Over Time in Total and Free C5 Concentration
Time frame: Up to 7 years
Observed Value in Absolute Reticulocyte Count
Time frame: Up to 7 years
Observed Value in Free Hemoglobin
Time frame: Up to 7 years
Observed Value in Haptoglobin
Time frame: Up to 7 years
Percent Change From Baseline in Absolute Reticulocyte Count
Time frame: Baseline, Week 25
Percent Change From Baseline in Free Hemoglobin
Time frame: Baseline, Week 25
Percent Change From Baseline in Haptoglobin
Time frame: Baseline, Week 25