SNPMiner Trials (Home Page)
Report for Mutation R885H
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There is one clinical trial.
Clinical Trials
1 An Open-Label, Single Arm Study to Evaluate the Efficacy and Safety of REGN3918 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Are Complement Inhibitor-Naive or Have Not Recently Received Complement Inhibitor Therapy
The primary objective of the study is to demonstrate a reduction in intravascular hemolysis by REGN3918 over 26 weeks of treatment in patients with active PNH who are treatment-naive to complement inhibitor therapy or have not recently received complement inhibitor therapy. The secondary objectives of the study are: - To evaluate the safety and tolerability of REGN3918. - To evaluate the effect of REGN3918 on parameters of intravascular hemolysis - To assess the concentrations of total REGN3918 in serum. - To evaluate the incidence of treatment-emergent anti-drug antibodies to REGN3918 over time - To evaluate the effect of REGN3918 on patient-reported outcomes (PROs) measuring fatigue and health-related quality of life
NCT03946748 Paroxysmal Nocturnal Hemoglobinuria (PNH) Drug: REGN3918 MeSH:Hemoglobinuria Hemoglobinuria, Paroxysmal
HPO:Hemoglobinuria Paroxysmal nocturnal hemoglobinuria
Key Exclusion Criteria: - Prior treatment with a complement inhibitor either within 6 months prior to screening visit or at any time where the patient was refractory to complement inhibitor therapy, in the opinion of the investigator (with the exception of eculizumab refractory patients due to the C5 variant R885H/C) - History of bone marrow transplantation - Body weight < 40 kilograms at screening visit - Peripheral blood absolute neutrophil count (ANC) <500/μL [<0.5 x 109/L] or peripheral blood platelet count <50,000/μL - Documented history of systemic fungal disease or unresolved tuberculosis, or evidence of active or latent tuberculosis infection (LTBI) during screening period - Any contraindication for receiving Neisseria meningitidis vaccination and antibiotic prophylaxis therapy as recommended in the study - Any active, ongoing infection within 2 weeks of screening or during the screening period - Any clinically significant abnormality identified at the time of screening that in the judgment of the Investigator or any sub-Investigator would preclude safe completion of the study or constrain endpoints assessment such as major systemic diseases, or patients with short life expectancy - Women who are pregnant, breastfeeding, or who have a positive pregnancy test at screening visit or day 1 NOTE: Other protocol defined Inclusion/Exclusion criteria apply. --- R885H ---
Primary Outcomes
Description: Defined as lactate dehydrogenase (LDH) ≤ 1.5 x upper limit of normal (ULN)
Measure: Proportion of patients achieving adequate control of their intravascular hemolysis Time: Week 4 through week 26Description: Defined as no post baseline transfusion of red blood cells (RBCs)
Measure: Proportion of patients achieving transfusion avoidance Time: Up to 26 weeksSecondary Outcomes
Description: Defined as the measurement of LDH) ≥ 2 x ULN concomitant with associated signs or symptoms at any time subsequent to an initial achievement of disease control.
Measure: Rate of breakthrough hemolysis Time: Up to 26 WeeksDescription: Defined as LDH ≤ 1.0 x ULN
Measure: Proportion of patients achieving normalization of their intravascular hemolysis Time: Week 4 through week 26Measure: Time to first LDH ≤ 1.5 x ULN Time: Up to week 26
Measure: Percentage of days with LDH ≤ 1.5 x ULN Time: Week 4 through week 26
Measure: Change in LDH levels Time: Baseline to week 26
Measure: Percent change in LDH levels Time: Baseline to week 26
Measure: Rate of transfusion with RBCs Time: Up to 26 weeks
Measure: Number of units of transfusion with RBCs Time: Up to 26 weeks
Measure: Change in RBC hemoglobin levels Time: Baseline to week 26
Measure: Change in free hemoglobin levels Time: Baseline to week 26
Measure: Change in total complement hemolytic activity assay (CH50) Time: Baseline to week 26
Measure: Percent change in CH50 Time: Baseline to week 26
Description: The FACIT-F is a 13-item, self-reported PRO measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related QoL in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a 4-point Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue.
Measure: Changes in scores of patient-reported outcomes as measured by FACIT-Fatigue Time: Baseline to week 26Description: EORTC QLQ-C30 is a self-reported, 30-item generic questionnaire developed to assess 15 domains: global health status scale, five functional scales (physical, role, emotional, cognitive, and social functioning) and nine symptom scales (fatigue, nausea, vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties). All the scales range from 0 to 100. A high score on the functional scales represents a high level of functioning, and a high score on the symptom scales represents a high level of symptomatology. A high score on the global QOL represents a high general quality of life.
Measure: Changes in scores of patient-reported outcomes as measured by European Organization for Research and Treatment of Cancer [EORTC]- Quality of life questionnaire-core 30 (QLQ-30) Time: Baseline to week 26Description: The EQ-5D-3L is a self-administered standardized instrument for use as a measure of health outcome. It is a health questionnaire that consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems.
Measure: Changes in scores of patient-reported outcomes as measured by EQ-5D-3L Time: Baseline to week 26Measure: Incidence and severity of treatment-emergent adverse events (TEAEs) Time: Up to 26 weeks
Measure: Safety measured by number of patients who experience abnormal laboratory values Time: Up to 26 weeks
Measure: Safety measured by number of patients who experience abnormal vital signs Time: Up to 26 weeks
Measure: Concentrations of total REGN3918 in serum Time: Up to week 26
Measure: Incidence of treatment-emergent anti-drug antibodies to REGN3918 Time: Up to week 26