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

NCT03013426 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: PRO16110118
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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).

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of NVX-508

  1 year

Study Arms (1)

NVX-508

EXPERIMENTAL

Administration of 1, 2 or 4 doses of NVX-508 at three dose levels; 0.05ml/kg. 0.1ml/kg and 0.17ml/kg in a 3 + 3 design.

Drug: NVX-508

Interventions

NVX-508 DRUG

Administration of NVX-508 emulsion intravenously

NVX-508

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of SCD without acute VOE and/or ACS.
• Age 18 years and older
• Adequate hematologic, renal and hepatic function, defined by:
• Absolute neutrophil count (ANC) ≥ 1.5 x109/L
• Platelet count ≥ 100 x 109/L,
• Hemoglobin ≥ 60 g/L
• International normalized ratio (INR) \< 1.5 x upper limit of normal (ULN)
• Activated partial thromboplastin time (APTT) \< 1.5 x ULN
• Plasma creatinine \< 1.5 x ULN
• Total bilirubin \< 2.5 x ULN (in the presence of Gilbert's syndrome or indirect hyperbilirubinemia caused by hemolysis)
• Aspartate transaminase (AST) \< 2.5 x ULN
• Alanine transaminase (ALT) \< 2.5 x ULN
• Ability of the prospective subject to understand and willingness to sign written informed consent document

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amma Owusu-Ansah, MD: lead
• NuvOx LLC: collaborator
• Noguchi Memorial Institute for Medical Research: collaborator

Related Publications (6)

• Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ. 2008 Jun;86(6):480-7. doi: 10.2471/blt.06.036673.

  PMID: 18568278 BACKGROUND

• Grosse SD, Odame I, Atrash HK, Amendah DD, Piel FB, Williams TN. Sickle cell disease in Africa: a neglected cause of early childhood mortality. Am J Prev Med. 2011 Dec;41(6 Suppl 4):S398-405. doi: 10.1016/j.amepre.2011.09.013.

  PMID: 22099364 BACKGROUND

• Johnson JL, Dolezal MC, Kerschen A, Matsunaga TO, Unger EC. In vitro comparison of dodecafluoropentane (DDFP), perfluorodecalin (PFD), and perfluoroctylbromide (PFOB) in the facilitation of oxygen exchange. Artif Cells Blood Substit Immobil Biotechnol. 2009;37(4):156-62. doi: 10.1080/10731190903043192. Epub 2009 Jun 22.

  PMID: 19548131 BACKGROUND

• Riess JG. Understanding the fundamentals of perfluorocarbons and perfluorocarbon emulsions relevant to in vivo oxygen delivery. Artif Cells Blood Substit Immobil Biotechnol. 2005;33(1):47-63. doi: 10.1081/bio-200046659.

  PMID: 15768565 BACKGROUND

• Grayburn PA, Weiss JL, Hack TC, Klodas E, Raichlen JS, Vannan MA, Klein AL, Kitzman DW, Chrysant SG, Cohen JL, Abrahamson D, Foster E, Perez JE, Aurigemma GP, Panza JA, Picard MH, Byrd BF 3rd, Segar DS, Jacobson SA, Sahn DJ, DeMaria AN. Phase III multicenter trial comparing the efficacy of 2% dodecafluoropentane emulsion (EchoGen) and sonicated 5% human albumin (Albunex) as ultrasound contrast agents in patients with suboptimal echocardiograms. J Am Coll Cardiol. 1998 Jul;32(1):230-6. doi: 10.1016/s0735-1097(98)00219-8.

  PMID: 9669275 BACKGROUND

• Correas JM, Meuter AR, Singlas E, Kessler DR, Worah D, Quay SC. Human pharmacokinetics of a perfluorocarbon ultrasound contrast agent evaluated with gas chromatography. Ultrasound Med Biol. 2001 Apr;27(4):565-70. doi: 10.1016/s0301-5629(00)00363-x.

  PMID: 11368867 BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Amma T Owusu-Ansah, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine and Clinical Director, Center for Translational and International Hematology

Study Record Dates

• First Submitted: January 3, 2017
• First Posted: January 6, 2017
• Study Start: July 1, 2018
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: July 16, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share