A Phase Ib Study of NVX-508 in Sickle Cell Disease

• Status: Withdrawn
• Trial end date: 2018-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This Phase 1b study in adults with sickle cell disease (SCD) in steady-state (non-acutely ill) aims to evaluate safety and toxicity of NVX-508 in a multi-dosing paradigm as well as to determine the maximum tolerated dose (MTD) in this population. The information gained from this study will be used in making decisions about the appropriate dose(s) and dosing schedule in future multicenter studies of the efficacy of NVX-508 in the treatment of vaso-occlusive episodes (VOE).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Amma Owusu-Ansah, MD
• Collaborators: Noguchi Memorial Institute for Medical Research; NuvOx LLC; NuvOx Pharma Pty Ltd

Criteria

Inclusion Criteria:

• Clinical diagnosis of SCD without acute VOE and/or ACS.

• Age 18 years and older

• Adequate hematologic, renal and hepatic function, defined by:

1. Absolute neutrophil count (ANC) ≥ 1.5 x109/L

2. Platelet count ≥ 100 x 109/L,

3. Hemoglobin ≥ 60 g/L

4. International normalized ratio (INR) < 1.5 x upper limit of normal (ULN)

5. Activated partial thromboplastin time (APTT) < 1.5 x ULN

6. Plasma creatinine < 1.5 x ULN

7. Total bilirubin < 2.5 x ULN (in the presence of Gilbert's syndrome or indirect hyperbilirubinemia caused by hemolysis)

8. Aspartate transaminase (AST) < 2.5 x ULN

9. Alanine transaminase (ALT) < 2.5 x ULN

• Ability of the prospective subject to understand and willingness to sign written informed consent document

Exclusion Criteria:

• Patients who have received any other investigational agent within 4 weeks before enrollment.

• Patients who have had a VOE/ACS in the previous 4 weeks before enrollment.

• Stroke or transient ischemic attack within 6 months before enrollment.

• Myocardial infarction within 6 months before enrollment, unstable angina, New York Heart Association class II or greater congestive heart failure, or uncontrolled hypertension (systolic BP > 160 mmHg and/or diastolic BP > 100 mmHg).

• Congenital long QT syndrome, or corrected QT interval ( QTc) > 450 milliseconds (msec) in males and > 470 mSec in females on EKG.

• Uncontrolled arrhythmia or any history of clinically significant arrhythmia in the past 6 months

• Clinically-significant chronic obstructive pulmonary disease or asthma that is not controlled by medication.

• A history of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ cancer or other solid tumors curatively treated with no evidence of disease for ≥ 2 years.

• Current anticoagulant or antiplatelet therapy, except for prophylactic doses of low molecular weight heparins or low-dose aspirin.

• History of allergic reactions attributed to compounds of similar chemical composition to NVX- 508.

• Women who are pregnant or breastfeeding.

• Inability to comply with study procedures.

• History or evidence of any other clinically-significant condition that, in the opinion of the investigator, would pose a risk to subject safety or interfere with study procedures, evaluation or completion.

• Patients with active VOE or ACS or other significant current acute complication of SCD.