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NCT03020017

NU-0129 in Treating Patients With Recurrent Glioblastoma or Gliosarcoma Undergoing Surgery

Completed EARLY_PHASE1 Results posted Last updated 26 August 2022
What this trial tests

EARLY_PHASE1 trial testing Laboratory Biomarker Analysis in Gliosarcoma in 8 participants. Completed in 19 August 2020.

Timeline
25 May 2017
Primary endpoint
6 September 2018
19 August 2020

Quick facts

Lead sponsorNorthwestern University
PhaseEARLY_PHASE1
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment8
Start date25 May 2017
Primary completion6 September 2018
Estimated completion19 August 2020
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Northwestern University

Who can join

18 and older, any sex, with Gliosarcoma or Recurrent Glioblastoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Patients With Adverse Events Primary · Up to 21 days after study drug administration

To evaluate the safety of intravenous NU-0129 in patients with recurrent GBM or GS, the number of adverse events will be assessed and will be graded according to the NCI's Common Terminology Criteria in Adverse Events (CTCAE) version 4.03 where the grading is as follows: Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Fatal

Experienced any AE
GroupValue95% CI
NU-0129 Treatment8
Experienced an AE related to NU-01289
GroupValue95% CI
NU-0129 Treatment4
Experienced any SAE
GroupValue95% CI
NU-0129 Treatment1
Experienced an SAE related to NU-0129
GroupValue95% CI
NU-0129 Treatment0
NU-0129 Concentration in Blood After Drug Administration Using Maximum Concentration Secondary · At 1, 3, 5, 10, 30, and 60 minutes, and 4, 8, and 24 hours post infusion

Blood samples will be collected post-infusion to analyze drug concentration at specific time points after drug administration. Median plasma concentrations of NU-0129 were derived from time profiles for both Seven different small interfering RNA (siRNA) and gold (Au) concentrations, with Au plasma concentration determined by inductively coupled plasma mass spectrometry (ICP-MS) and siRNA concentration assessed by liquid chromatography-high performance liquid chromatography (LC-HPLC) using an atto dye-labeled PNA probe.

siRNA maximum observed plasma concentration
GroupValue95% CI
NU-0129 Treatment62.122.8 – 123
Au maximum observed plasma concentration
GroupValue95% CI
NU-0129 Treatment42903120 – 7140
Biodistribution of NU-0129 in Tumor Tissue Secondary · At time of surgery

Tissue will be collected during the scheduled surgery and assayed with Inductively Coupled Plasma Mass Spectrometry (ICP-MS) to analyze the concentration of particles in various parts of tumor tissue. To analyze spatial distribution of Au within tumor tissue, synchrotron XFM elemental maps of GBM tissue slices were acquired at micron and submicron resolution and matched to adjacent hematoxylin and eosin (H\&E)- and Ki67-stained tumor sections. Approximate percentage of gold (Au) found in cancer cells is reported below.

GroupValue95% CI
NU-0129 Treatment20.5± 8.15
Feasibility of Giving NU-0129 as a Standard Treatment Secondary · At time of infusion (8-48 hours prior to resection) and during surgery

Feasibility will be calculated as the rate of successful production, delivery, and administration of the investigational product and subsequent resection.

Number of patients who had drug infused successfully
GroupValue95% CI
NU-0129 Treatment8
Number of patient who underwent subsequent resection
GroupValue95% CI
NU-0129 Treatment8
NU-0129 Concentration in Blood After Drug Administration Using Half-life Secondary · At 1, 3, 5, 10, 30, and 60 minutes, and 4, 8, and 24 hours post infusion

Blood samples will be collected post-infusion to analyze drug concentration at specific time points after drug administration. Median plasma concentrations of NU-0129 were derived from time profiles for both Seven different small interfering RNA (siRNA) and gold (Au) concentrations, with Au plasma concentration determined by inductively coupled plasma mass spectrometry (ICP-MS) and siRNA concentration assessed by liquid chromatography-high performance liquid chromatography (LC-HPLC) using an atto dye-labeled PNA probe.

siRNA half-life
GroupValue95% CI
NU-0129 Treatment0.060.02 – 0.16
Au half-life
GroupValue95% CI
NU-0129 Treatment1812 – 23

Adverse events — posted to ClinicalTrials.gov

Time frame: Patients were monitored for adverse events from the time of NU-0129 infusion through 21 days post infusion. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

NU-0129 Treatment
Serious: 1/8 (13%)
Deaths: 0/8

Serious adverse events (1 terms)

ReactionSystemNU-0129 Treatment
Cerebrospinal fluid leakageNervous system disorders
Other adverse events (6 terms — click to expand)

ReactionSystemNU-0129 Treatment
Lymphocyte count decreasedInvestigations
HypophosphatemiaMetabolism and nutrition disorders
Alkaline phosphatase increasedInvestigations
Platelet count decreasedInvestigations
White blood cell decreasedInvestigations
HypertensionVascular disorders

Most-reported serious reactions: Cerebrospinal fluid leakage.

Data from ClinicalTrials.gov NCT03020017 adverse events section.

Sponsor's own description

The purpose of this research study is to evaluate the safety of the study drug, NU-0129, based on Spherical Nucleic Acid (SNA) platform when infused in patients with recurrent glioblastoma multiforme or gliosarcoma. The SNA consists of nucleic acids arranged on the surface of a small spherical gold nanoparticle. This is a first-in-human trial to determine the safety of NU-0129. NU-0129 can cross the blood brain barrier (a filtering mechanism that carry blood to the brain). Once within the tumor, the nucleic acid component is able to target a gene called Bcl2L12 that is present in glioblastoma multiforme, and is associated with tumor growth. This gene prevents tumor cells from apoptosis, which is the process of programmed cell death, thus promoting tumor growth. Researchers think that targeting the Bcl2L12 gene with NU-0129 will help stop cancer cells from growing.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Blood-Brain Barrier: From Physiology to Disease and Back.
    Sweeney MD, Zhao Z, Montagne A, Nelson AR, et al · · 2019 · cited 1647× · PMID 30280653 · DOI 10.1152/physrev.00050.2017
  2. Noncoding RNA therapeutics - challenges and potential solutions.
    Winkle M, El-Daly SM, Fabbri M, Calin GA. · · 2021 · cited 1123× · PMID 34145432 · DOI 10.1038/s41573-021-00219-z
  3. Therapeutic siRNA: state of the art.
    Hu B, Zhong L, Weng Y, Peng L, et al · · 2020 · cited 991× · PMID 32561705 · DOI 10.1038/s41392-020-0207-x
  4. Nanoparticles in the clinic: An update.
    Anselmo AC, Mitragotri S. · · 2019 · cited 976× · PMID 31572799 · DOI 10.1002/btm2.10143
  5. Current Challenges and Opportunities in Treating Glioblastoma.
    Shergalis A, Bankhead A, Luesakul U, Muangsin N, et al · · 2018 · cited 612× · PMID 29669750 · DOI 10.1124/pr.117.014944
  6. Gold Nanoparticles in Diagnostics and Therapeutics for Human Cancer.
    Singh P, Pandit S, Mokkapati VRSS, Garg A, et al · · 2018 · cited 520× · PMID 29986450 · DOI 10.3390/ijms19071979
  7. Molecular mechanisms of cell death in neurological diseases.
    Moujalled D, Strasser A, Liddell JR. · · 2021 · cited 513× · PMID 34099897 · DOI 10.1038/s41418-021-00814-y
  8. Review on metal nanoparticles as nanocarriers: current challenges and perspectives in drug delivery systems.
    Chandrakala V, Aruna V, Angajala G. · · 2022 · cited 286× · PMID 35005431 · DOI 10.1007/s42247-021-00335-x

Verify or expand the search:

Other trials of Laboratory Biomarker Analysis

Trials testing the same drug.

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Other Northwestern University trials

Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03020017.

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