Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Immunoglobulin Replacement Therapy for Immunoglobulin G Subclass 2 Deficient Patients With Bronchiectasis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03737617
Recruitment Status : Not yet recruiting
First Posted : November 9, 2018
Last Update Posted : April 30, 2019
Sponsor:
Collaborator:
NHS Lothian
Information provided by (Responsible Party):
University of Edinburgh

Brief Summary:

Bronchiectasis is a common chronic lung condition where patients have permanent airways damage leading to daily symptoms of cough, sputum production and recurrent respiratory tract infections.

Preliminary studies in our research group have found a severe deficiency of the immune system as a rare cause of bronchiectasis (called immunoglobulin G subclass 2 deficiency) and occurs in about 1 in 20 bronchiectasis patients. The pilot work shows that these patients have more chest infections and their lung function deteriorates more rapidly.

There are no trials to date to guide doctors to decide whether we should replace this deficiency from donated blood or not. The aim with treatment is to prevent disease progression and avoid the need for long term antibiotics.

This trial will help us understand how this treatment works and its acceptability to patients. This study will help us decide whether investigators should pursue future formalised trials in many centres throughout the UK and how investigators should evaluate such a treatment.

We are looking to recruit 20 patients to this study 10 of which will receive weekly replacement therapy and the remaining 10 will receive standard care.


Condition or disease Intervention/treatment Phase
Bronchiectasis Immunoglobulin Subclass Deficiency Drug: Cuvitru 20 % Injectable Solution Phase 4

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 1 Group receiving active immunoglobulin replacement therapy
Masking: None (Open Label)
Masking Description: 1 group receiving standard care
Primary Purpose: Treatment
Official Title: Immunoglobulin Replacement Therapy for Immunoglobulin G Subclass 2 Deficient Patients With Bronchiectasis- A Proof of Concept Study
Estimated Study Start Date : December 5, 2019
Estimated Primary Completion Date : May 1, 2021
Estimated Study Completion Date : December 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Active arm
Weekly subcutaneous immunoglobulin therapy (0.1g/Kg) Cuvitru 20% Injectable Solution for 1 Year
Drug: Cuvitru 20 % Injectable Solution
Active

No Intervention: Control
Standard Care arm without immunoglobulin replacement therapy



Primary Outcome Measures :
  1. Change in sputum bacterial load [ Time Frame: 52 weeks ]
    With IgG replacement therapy, does the sputum bacterial load change in treated versus untreated group

  2. Proportion with bacterial load >=10(6) colony forming units/ml [ Time Frame: 52 weeks ]
    With IgG replacement therapy, does the frequency with >=10(6) colony forming units/ml change in treated versus untreated group?


Secondary Outcome Measures :
  1. Change in sputum colour [ Time Frame: 26 and 52 weeks ]
    Does sputum colour change in treated versus untreated group?

  2. Change in sputum volume [ Time Frame: 26 and 52 weeks ]
    Does 24 hour sputum volume change in treated versus untreated group

  3. Change in sputum microbiome diversity [ Time Frame: 52 weeks ]
    Does Sputum microbiome change in treated versus untreated group

  4. Change of forced expired volume in 1 second [ Time Frame: 26 and 52 weeks ]
    Does forced expired volume in 1 second change in treated versus untreated group

  5. Change of forced expired volume in 1 second % predicted [ Time Frame: 26 and 52 weeks ]
    Does forced expired volume in 1 second change % predicted in treated versus untreated group

  6. Change of forced vital capacity [ Time Frame: 26 and 52 weeks ]
    Does forced vital capacity in treated versus untreated group

  7. Change of forced vital capacity % predicted [ Time Frame: 26 and 52 weeks ]
    Does forced vital capacity % predicted in treated versus untreated group

  8. Change of incremental shuttle walk test [ Time Frame: 26 and 52 weeks ]
    Does the incremental shuttle walk test change in treated versus untreated group

  9. Change of cough related quality of life using Leicester Cough Questionnaire mean score [ Time Frame: 26 and 52 weeks ]
    Does cough related quality of life change in treated versus untreated group using the Leicester Cough Questionnaire mean score (range 3-21)

  10. Change of cough related quality of life using Leicester Cough Questionnaire with 1.3 Unit or greater improvement [ Time Frame: 26 and 52 weeks ]
    Does cough related quality of life change in treated versus untreated group using the Leicester Cough Questionnaire proportion that have 1.3 or more Unit improvement (minimum clinically important difference)

  11. Change of quality of life using St George's Respiratory Questionnaire with 4Unit or greater improvement [ Time Frame: 26 and 52 weeks ]
    Does quality of life change in treated versus untreated group using the St George's Respiratory Questionnaire proportion that have 4 Unit or more improvement (minimum clinically important difference)

  12. Change of quality of life using St George's Respiratory Questionnaire mean score [ Time Frame: 26 and 52 weeks ]
    Does quality of life change in treated versus untreated group using the St George's Respiratory Questionnaire mean score (range 0-100)

  13. Change of sputum myeloperoxidase [ Time Frame: 26 and 52 weeks ]
    Does sputum myeloperoxidase change in treated versus untreated group

  14. Change of sputum elastase [ Time Frame: 26 and 52 weeks ]
    Does sputum elastase change in treated versus untreated group

  15. Change of sputum interleukin 8 [ Time Frame: 26 and 52 weeks ]
    Does sputum interleukin 8 change in treated versus untreated group

  16. Change of total IgG and subclasses [ Time Frame: 26 and 52 weeks ]
    Do serum IgG and subclasses change in treated versus untreated group

  17. Change of serum white cell count [ Time Frame: 26 and 52 weeks ]
    Do serum white cell count change in treated versus untreated group

  18. Change of serum C reactive protein [ Time Frame: 26 and 52 weeks ]
    Do serum C reactive protein change in treated versus untreated group

  19. Change of serum erythrocyte sedimentation rate [ Time Frame: 26 and 52 weeks ]
    Do serum erythrocyte sedimentation rate change in treated versus untreated group

  20. Change of serum intercellular adhesion molecule 1 [ Time Frame: 26 and 52 weeks ]
    Do serum intercellular adhesion molecule 1 change in treated versus untreated group

  21. Change of phagocytosis and killing of Pseudomonas aeruginosa [ Time Frame: 26 and 52 weeks ]
    Does peripheral blood neutrophil phagocytosis and killing of Pseudomonas aeruginosa change in treated versus untreated group

  22. Change of phagocytosis and killing of Staphylococcus aureus [ Time Frame: 26 and 52 weeks ]
    Does peripheral blood neutrophil phagocytosis and killing of Staphylococcus aureus change in treated versus untreated group

  23. Proportion with specific antibody deficiency [ Time Frame: Baseline ]
    Is there antibody deficiency with pneumococcal vaccination

  24. Time to first exacerbation requiring antibiotic therapy [ Time Frame: 52 weeks ]
    Is the time to first exacerbation requiring antibiotic therapy change in treated versus untreated group

  25. Number of exacerbations [ Time Frame: 52 weeks ]
    Does the number of exacerbations change in treated versus untreated group

  26. Frequency of exacerbations [ Time Frame: 52 weeks ]
    Does the mean exacerbations change in treated versus untreated group

  27. Number of participants with side effects [ Time Frame: 26 and 52 weeks ]
    What are the number of participants with side effects of IgG therapy

  28. Compliance rates of IgG therapy [ Time Frame: 26 and 52 weeks ]
    What are the compliance rates of IgG therapy

  29. Completion rates of IgG therapy [ Time Frame: 26 and 52 weeks ]
    What are the completion rates of IgG therapy



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria (need to meet all criteria below)

  1. Bronchiectasis as the primary respiratory diagnosis.
  2. Aged 18 years or older.
  3. Bronchiectasis Severity Index >5 (0-4 mild; 5-8 moderate; >9 severe) or 3 or more exacerbations in the preceding year.
  4. Patients with IgG2 deficiency<2.41g/L.
  5. Able to provide written, informed consent
  6. In the opinion of the research physician, the patient will be able to comply with the requirements of the trial protocol
  7. Meets the co-enrolment criteria

Exclusion criteria (will be excluded if they have any item below)

  1. Cystic fibrosis
  2. Pregnancy or breast feeding
  3. Women of childbearing potential not taking appropriate contraception. Acceptable contraception in women of childbearing age is a "highly effective" contraceptive measure as defined by the Clinical Trials Facilitation Group (http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf) and includes combined (oestrogen and progesterone containing) or progesterone-only contraception associated with inhibition of ovulation, or intrauterine device or bilateral tubal occlusion. Contraception must be continued for a minimum of 30 days after the end of the IMP dosing schedule.
  4. Active malignancy
  5. Active co-morbid illness
  6. Current smokers or ex-smokers less than 1 year
  7. Known hypersensitivity to L-proline or Polysorbate 80
  8. Known hyperprolinaemia type I or II
  9. Known hypersensitivity to the IMP active substance or excipients (i.e. human normal immunoglobulin, Glyine or water for injections).
  10. Severe IgA deficiency and a history of hypersensitivity to human immunoglobulin treatment
  11. Known IgG1 deficiency
  12. Known thrombophilic disorders or thrombotic events
  13. Previously participated in this trial
  14. Severe renal impairment (creatinine clearance of less than 30 ml/minute)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03737617


Contacts
Layout table for location contacts
Contact: Fiach O'Mahony +441312429418 fiach.o'mahony@ed.ac.uk

Locations
Layout table for location information
United Kingdom
Royal Infirmary of Edinburgh Not yet recruiting
Edinburgh, United Kingdom, EH16 4SA
Contact: Fiach O'Mahony    +441312429418 ext +441312429418    fiach.o'mahony@ed.ac.uk   
Principal Investigator: Adam T Hill, MBChB, MD         
Sponsors and Collaborators
University of Edinburgh
NHS Lothian
Investigators
Layout table for investigator information
Principal Investigator: Adam T Hill, MBChB MD NHS Lothian and University of Edinburgh

Layout table for additonal information
Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT03737617     History of Changes
Other Study ID Numbers: IgG2CT001
First Posted: November 9, 2018    Key Record Dates
Last Update Posted: April 30, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No plan to share IPD- will present overall data

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Edinburgh:
Replacement therapy
Microbiology
Exacerbations
Bronchiectasis
Immunoglobulin G subclass 2

Additional relevant MeSH terms:
Layout table for MeSH terms
Bronchiectasis
Bronchial Diseases
Respiratory Tract Diseases
Immunoglobulins
Antibodies
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs