SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03946748

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

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. - To evaluate the effect of REGN3918 on patient-reported outcomes (PROs) measuring fatigue and health-related quality of life

NCT03946748 Paroxysmal Nocturnal Hemoglobinuria (PNH)
MeSH: Hemoglobinuria Hemoglobinuria, Paroxysmal
HPO: Hemoglobinuria Paroxysmal nocturnal hemoglobinuria

1 Interventions

Name: REGN3918

Description: Single intravenous (IV) dose, then a subcutaneous (SC) dose once weekly (QW).

Type: Drug

REGN3918


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 26

Description: Defined as no post baseline transfusion of red blood cells (RBCs)

Measure: Proportion of patients achieving transfusion avoidance

Time: Up to 26 weeks

Secondary 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 Weeks

Description: Defined as LDH ≤ 1.0 x ULN

Measure: Proportion of patients achieving normalization of their intravascular hemolysis

Time: Week 4 through week 26

Measure: 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 26

Description: 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 Cooperative Oncology Group [EORTC]- Quality of life questionnaire-core 30 (QLQ-30)

Time: Baseline to week 26

Description: 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 26

Measure: 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

Purpose: Treatment

Sequential Assignment


There is one SNP

SNPs


1 R885H

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) <1,000/μL [<1.0 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 ---



HPO Nodes


HPO:
Hemoglobinuria
Genes 11
CFI NT5C3A CFH CD46 PIEZO1 PIGT CD59 HELLPAR G6PD CASK PIGA
Paroxysmal nocturnal hemoglobinuria
Genes 3
PIGT CD59 PIGA