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

NCT03737617 | Withdrawn Phase 4

• 1 other identifier: IgG2CT001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Bronchiectasis; Immunoglobulin Subclass Deficiency

Keywords

Replacement therapy; Microbiology; Exacerbations; Bronchiectasis; Immunoglobulin G subclass 2

Outcome Measures

Primary Outcomes (2)

• Change in sputum bacterial load

  With IgG replacement therapy, does the sputum bacterial load change in treated versus untreated group

  52 weeks

• Proportion with bacterial load >=10(6) colony forming units/ml

  With IgG replacement therapy, does the frequency with \>=10(6) colony forming units/ml change in treated versus untreated group?

  52 weeks

Secondary Outcomes (29)

• Change in sputum colour

  26 and 52 weeks

• Change in sputum volume

  26 and 52 weeks

• Change in sputum microbiome diversity

  52 weeks

• Change of forced expired volume in 1 second

  26 and 52 weeks

• Change of forced expired volume in 1 second % predicted

  26 and 52 weeks

Study Arms (2)

Active arm

EXPERIMENTAL

Weekly subcutaneous immunoglobulin therapy (0.1g/Kg) Cuvitru 20% Injectable Solution for 1 Year

Drug: Cuvitru 20 % Injectable Solution

Control

NO INTERVENTION

Standard Care arm without immunoglobulin replacement therapy

Interventions

Cuvitru 20 % Injectable Solution DRUG

Active

Active arm

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• Cystic fibrosis
• Pregnancy or breast feeding
• 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.
• Active malignancy
• Active co-morbid illness
• Current smokers or ex-smokers less than 1 year
• Known hypersensitivity to L-proline or Polysorbate 80
• Known hyperprolinaemia type I or II
• Known hypersensitivity to the IMP active substance or excipients (i.e. human normal immunoglobulin, Glyine or water for injections).
• Severe IgA deficiency and a history of hypersensitivity to human immunoglobulin treatment
• Known IgG1 deficiency
• Known thrombophilic disorders or thrombotic events
• Previously participated in this trial
• Severe renal impairment (creatinine clearance of less than 30 ml/minute)

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator

Study Sites (1)

Royal Infirmary of Edinburgh

Edinburgh, EH16 4SA, United Kingdom

Location

MeSH Terms

Conditions

Bronchiectasis

Interventions

Hizentra

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases

Study Officials

• Adam T Hill, MBChB MD

  NHS Lothian and University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: 1 group receiving standard care
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 1 Group receiving active immunoglobulin replacement therapy

Study Record Dates

• First Submitted: July 19, 2017
• First Posted: November 9, 2018
• Study Start: August 5, 2022
• Primary Completion: August 1, 2024
• Study Completion: December 1, 2024
• Last Updated: September 29, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)