NCT03103555

Brief Summary

This is pilot study aimed to investigate the application of proteosome inhibitor, Bortezomib in treatment of patients with neutralizing autoantibody to IFN-γ. The investigators hypothesis is that bortezomib will reduce the antibody level and restore interferon-gamma function, resulting in clinical improvement and should be well-tolerated and safe for use in patients with autoantibody to IFN-γ.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
5

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Feb 2017

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 27, 2017

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

April 1, 2017

Completed
5 days until next milestone

First Posted

Study publicly available on registry

April 6, 2017

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2018

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2019

Completed
Last Updated

April 6, 2017

Status Verified

April 1, 2017

Enrollment Period

1.7 years

First QC Date

April 1, 2017

Last Update Submit

April 1, 2017

Conditions

Adult-onset Immunodeficiency

Keywords

Anti-interferon gamma autoantibody

Outcome Measures

Primary Outcomes (3)

  • Titers of anti-interferon-gamma antibody after treatment with bortezomib

    Change in titers of anti-interferon-gamma antibody after treatment with

    8 weeks after first dose of bortezomib (after completion 2 cycles of bortezomib)

  • Titers of anti-interferon-gamma antibody after treatment with bortezomib and cyclophosphamide

    Change in titers of anti-interferon-gamma antibody after treatment with bortezomib and cyclophosphamide

    1 year after first dose of bortezomib

  • Adverse event

    Grade 4 adverse event (probably related)

    6 months after first dose of bortezomib (after completion 4 months of cyclophosphamide)

Secondary Outcomes (1)

  • Disease relapse

    6 month and 1 year after first dose of bortezomib

Study Arms (1)

Bortezomib and cyclophosphamide

EXPERIMENTAL

Two cycles of bortezomib administered subcutaneously, followed by 4 months of low dose oral cyclophosphamide.

Drug: BortezomibDrug: Cyclophosphamide

Interventions

BortezomibDRUG

Bortezomib will be subcutaneously administered in 2 treatment cycles with 4 injections of 1.3 mg Bortezomib /m2 body surface per cycle.

Also known as: Velcade
Bortezomib and cyclophosphamide
CyclophosphamideDRUG

Low dose cyclophosphamide will be given orally for 4 month after completion 2 cycles of bortezomib

Also known as: Endoxan
Bortezomib and cyclophosphamide

Eligibility Criteria

Age21 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Age 21 - 60 years
  • Positive anti-interferon-gamma autoantibody
  • Anti-HIV negative
  • Past or current infection with opportunistic infection (OI) such as nontuberculous mycobacteria, proven by culture
  • Ability to give written consent, informed written consent
  • Negative pregnancy test in premenopausal woman
  • Receving antimicrobial for treatment of OI for at least one month.

You may not qualify if:

  • Pregnancy or lactation
  • Absolute neutrophil count \<1.5 × 109/ L or platelet count \<100× 109/ L or hemoglobin level \< 8 g/dL
  • Past history of myocardial infarction or heart failure within 6 months before enrollment or prolonged QT interval \> 450 msec at screening
  • Renal insufficiency (GFR \< 30 ml/min)
  • Abnormal liver function test (AST\> 3 times of UNL)
  • Known cancer or receiving other immunosuppressive agent
  • Known intolerability to Bortezomib

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Faculty of Medicine Siriraj Hospital, Mahidol University

Bangkok, Bangkok, 10700, Thailand

RECRUITING

Related Publications (1)

  • Angkasekwinai N, Suputtamongkol Y, Tantibhedhyangkul W, Onlamoon N, Phoompoung P, Pithukpakorn M, Karuphong E, Pusuwan P, Angkasekwinai P. Efficacy of Bortezomib for Treating Anti-Interferon-Gamma Autoantibody-Associated Adult-Onset Immunodeficiency Syndrome. Clin Infect Dis. 2024 Apr 10;78(4):1033-1042. doi: 10.1093/cid/ciad676.

    PMID: 37947190DERIVED

MeSH Terms

Interventions

BortezomibCyclophosphamide

Intervention Hierarchy (Ancestors)

Boronic AcidsAcids, NoncarboxylicAcidsInorganic ChemicalsBoron CompoundsOrganic ChemicalsPyrazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Nasikarn Angkasekwinai, MD.

    Faculty of Mdicine Siriraj Hospital, Mahidol University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Nasikarn Angkasekwinai, MD.

CONTACT

6681-8708766nasikarn@gmail.com

Yupin Suputtamongkol, MD.

CONTACT

662-4197783ysuputtamongkol@gmail.com

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 1, 2017

First Posted

April 6, 2017

Study Start

February 27, 2017

Primary Completion

November 1, 2018

Study Completion

November 1, 2019

Last Updated

April 6, 2017

Record last verified: 2017-04

Data Sharing

IPD Sharing
Will not share

Locations

TH(1)