Rituximab and Belimumab Combination Therapy in PR3 Vasculitis

NCT03967925 | Unknown Phase 2 DMC

• 1 other identifier: 206852
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 6

Brief Summary

Mechanistic study to assess whether dual B-cell immunotherapy by co-administration of rituximab and belimumab will result in improvements in biological endpoints, functional outcomes and clinical status compared to rituximab with placebo.

Conditions

ANCA Associated Vasculitis; Granulomatosis With Polyangiitis

Keywords

proteinase 3

Outcome Measures

Primary Outcomes (1)

• Time to PR3 ANCA negativity

  ELISA analysis at different time points to determine when PR3 ANCA can no longer be detected

  Analysed at 24 months

Secondary Outcomes (4)

• Proportion of participants with PR3 ANCA negativity

  2 years

• Change from baseline of certain cell subsets

  2 years

• Time to clinical remission

  2 years

• Incidence of serious adverse events (SAEs)

  2 years

Study Arms (2)

Belimumab

ACTIVE COMPARATOR

Weekly 200mg SC injections of belimumab for 12 months

Drug: Belimumab; Drug: Rituximab; Drug: Prednisolone

Belimumab placebo

PLACEBO COMPARATOR

Weekly SC injections of belimumab placebo for 12 months

Drug: Rituximab; Drug: Prednisolone

Interventions

Belimumab DRUG

Sub-cutaneous injection

Also known as: Benlysta

Belimumab

Rituximab DRUG

IV infusion 1g x 2

Also known as: Truxima

Belimumab; Belimumab placebo

Prednisolone DRUG

20mg prednisolone tapering dose

Also known as: prednisone

Belimumab; Belimumab placebo

Eligibility Criteria

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

You may qualify if:

• Participants must be 18 of age
• Have a diagnosis of AAV (granulomatosis with polyangiitis or microscopic polyangiitis)
• Have PR3 ANCA positivity by ELISA at screening
• Have active disease defined by one major or three minor disease activity items on BVAS/WG
• Be capable of giving signed informed consent

You may not qualify if:

• MPO ANCA or anti-GBM antibody positivity by ELISA at screening
• Presence of pulmonary haemorrhage with hypoxia at screening
• Estimated glomerular filtration rate (eGFR) \<30 ml/min/1.73m2 at screening
• Have an acute serious or chronic infection at screening
• Have received any B cell targeted therapy within 364 days of Day 1
• Have received any steroid injection (e.g., intramuscular \[IM\], intraarticular, or IV) within 60 days of Day 1 (unless given during or 14 days before screening period)
• Have received \>1.5mg methylprednisolone (IV) between 14 days prior to screening and Day 1 (including Day 1).
• Have received oral prednisolone \>10mg/day (or equivalent) on average over the 30 days prior to screening
• Have undetectable peripheral blood B cells at screening
• Have IgG \<400mg/dl at screening

Sponsors & Collaborators

• Rachel Jones: lead
• GlaxoSmithKline: collaborator
• Medical Research Council: collaborator
• Imperial College London: collaborator
• University College, London: collaborator
• Newcastle University: collaborator
• University of Glasgow: collaborator
• University of Cambridge: collaborator

Study Sites (6)

Addenbrooke's Hospital

Cambridge, United Kingdom

Location

Glasgow Royal Infirmary

Glasgow, United Kingdom

Location

Imperial College London

London, United Kingdom

Location

Royal Free Hospital

London, United Kingdom

Location

Royal Freemann Hospital

Newcastle, United Kingdom

Location

Nottingham University Hospitals

Nottingham, United Kingdom

Location

Related Publications (2)

• McClure ME, Gopaluni S, Wason J, Henderson RB, Van Maurik A, Savage CCO, Pusey CD, Salama AD, Lyons PA, Lee J, Mynard K, Jayne DR, Jones RB; on behalf the COMBIVAS investigators. A randomised study of rituximab and belimumab sequential therapy in PR3 ANCA-associated vasculitis (COMBIVAS): design of the study protocol. Trials. 2023 Mar 11;24(1):180. doi: 10.1186/s13063-023-07218-y.

  PMID: 36906660 DERIVED

• Serling-Boyd N, Wallace ZS. Management of primary vasculitides with biologic and novel small molecule medications. Curr Opin Rheumatol. 2021 Jan;33(1):8-14. doi: 10.1097/BOR.0000000000000756.

  PMID: 33164993 DERIVED

MeSH Terms

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Granulomatosis with Polyangiitis

Interventions

belimumab; Rituximab; Prednisolone; Prednisone

Condition Hierarchy (Ancestors)

Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols

Study Officials

• Rachel B Jones

  Cambridge University Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Consultant Nephrologist

Study Record Dates

• First Submitted: January 18, 2019
• First Posted: May 30, 2019
• Study Start: February 1, 2019
• Primary Completion: April 1, 2023
• Study Completion: November 1, 2023
• Last Updated: March 8, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (6)