Efficacy and Safety of Namilumab for Moderate-to-severe Axial Spondyloarthritis (NAMASTE)

A Phase 2a Study to Evaluate the Safety and Efficacy of Namilumab in Subjects With Moderate-to-severely Active Axial Spondyloarthritis

The study will assess the effect of namilumab, a GM-CSF inhibitor, on the clinical response in subjects with axial spondyloarthritis. Subjects will receive treatment with either namilumab or placebo.

Study Overview

• Status: Completed
• Conditions: Axial Spondyloarthritis
• Intervention / Treatment: Biological: Placebo; Biological: Namilumab

Detailed Description

A phase 2a proof-of-concept, randomised, double-blind, placebo-controlled study to evaluate the safety/tolerability and efficacy of 4 subcutaneous injections of namilumab (150 mg) given over 10 weeks in subjects with moderate-to-severely active axial spondyloarthritis including those previously exposed to anti- TNF therapy (NAMASTE study).

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Bath, United Kingdom
    • Royal United Hospitals Bath
  • Birmingham, United Kingdom
    • University Hospital Birmingham
  • Coventry, United Kingdom
    • University Hospital Coventry and Warwickshire
  • London, United Kingdom
    • Northwick Park Hospital
  • London, United Kingdom
    • Whipps Cross Hospital
  • Norwich, United Kingdom
    • Norfolk and Norwich University Hospital
  • Oxford, United Kingdom
    • Oxford University Hospital
  • Reading, United Kingdom
    • Royal Berkshire Hospital
  • Stoke-on-Trent, United Kingdom
    • Haywood Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 and ≤ 75 years of age.
• Diagnosis of axSpA by an appropriately qualified physician and classified using ASAS criteria ≥ 3 months prior to Baseline.
• Bath Ankylosing Spondylitis Disease Activity Index score ≥ 4 and spinal pain score ≥ 40, at screening and Baseline.
• MRI evidence of active axSpA ≤ 6 (ideally ≤ 3) months prior to randomisation using ASAS criteria.
• Stable NSAID use prior to study entry.
• Stable use of MTX, sulfasalazine or leflunomide prior to study entry.
• Stable oral corticosteroid dose prior to study entry.
• Capable of giving signed informed consent.
• Inadequately responded to or experienced intolerance to previous treatment with an anti-TNF agent (some subjects).

Exclusion Criteria:

• Current diagnosis of axSpA with a BASDAI > 4 but no evidence of inflammation on MRI.
• Discontinued biologic therapy < 8 weeks prior to Baseline.
• Previous or current use of oral corticosteroid as defined in protocol.
• Received intra-articular or i.v. corticosteroids prior to or during Screening.
• Received anti-IL-17A or anti-IL-12/23 therapy.
• Received cyclosporine, tacrolimus or mycophenolate mofetil prior to Baseline.
• Previously received stem cell transplantation.
• Infection(s) requiring treatment with i.v. anti-infectives or oral anti-infectives prior to Baseline.
• Abnormal screening laboratory and other analyses.
• Receipt of any live vaccine within 2 weeks prior to randomisation, or will require live vaccination during study participation.
• Evidence of current or prior dysplasia or history of malignancy.
• Has had any uncontrolled and/or clinically significant illness, hospitalisation, or any surgical procedure requiring general anaesthesia prior to Screening, or any planned surgical procedure within 6 months after randomisation.
• Known current or previous interstitial lung disease.
• Positive pregnancy test at Screening (serum) or Baseline (urine).
• Female subjects who are breastfeeding or considering becoming pregnant during the study.
• Considered by the Investigator to be an unsuitable candidate for the study.
• Received any investigational agent or procedure within 30 days or 5 half-lives prior to Baseline.
• Related to or a dependent of the site staff, or a member of the site staff.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo solution administered by subcutaneous injection on 4 occasions over 10 weeks	Biological: Placebo; Placebo solution for subcutaneous injection.
Experimental: Namilumab; Namilumab (150 mg) administered by subcutaneous injection on 4 occasions over 10 weeks	Biological: Namilumab; Namilumab solution for subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Proportion of Subjects Who Achieved ASAS20 Clinical Response	The primary endpoint was the proportion of subjects who achieved an Assessment in Ankylosing Spondylitis with 20% improvement (ASAS20) clinical response at Week 12. An ASAS20 clinical response was defined as an improvement of at least 20% and an absolute improvement of at least 10 units on a 0 to 100 scale in at least three of the following four domains collected in the electronic case report form (eCRF) and no worsening in the fourth domain: Subject's Global Assessment of Disease Status, Subject's Assessment of Spinal Pain, function (Bath Ankylosing Spondylitis Functional Index [BASFI]) and inflammation (last two questions of the BASDAI). Lower values within the individual domains represent less severe symptoms.	Weeks 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Who Achieved ASAS40 Clinical Response at Week 12	Proportion of subjects who achieved Assessment in Ankylosing Spondylitis with 40% improvement (ASAS40) response at Week 12	Week 12
Proportion of Subjects Who Achieved an ASAS20 Clinical Response at Week 6	Proportion of subjects who achieved an ASAS20 clinical response at Week 6	Week 6
Proportion of Subjects Who Achieved Ankylosing Spondylitis Disease Activity Score C-reactive Protein (ASDAS-CRP) Response at Weeks 6	Proportion (percentage) of subjects who achieved Ankylosing Spondylitis Disease Activity Score C-reactive Protein (ASDAS-CRP) response at Week 6, Clinically Important Improvement	Week 6
Proportion of Subjects Who Achieved Clinically Important ASDAS-CRP Score at Week 12	Proportion of Subjects Who Achieved Clinically Important ASDAS-CRP Score at Week 12, Clinically Important Improvement	Week 12

Collaborators and Investigators

• Sponsor: Izana Bioscience Ltd.
• Collaborators: IQVIA Pty Ltd; Innovate UK
• Investigators: Principal Investigator: Peter C Taylor, PhD, Botnar Research Centre, University of Oxford

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2018
• Primary Completion (Actual): February 4, 2020
• Study Completion (Actual): February 4, 2020

Study Registration Dates

• First Submitted: July 17, 2018
• First Submitted That Met QC Criteria: August 7, 2018
• First Posted (Actual): August 9, 2018

Study Record Updates

• Last Update Posted (Actual): March 8, 2022
• Last Update Submitted That Met QC Criteria: January 5, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Bone Diseases, Infectious; Spondylitis; Spondylarthritis
• Other Study ID Numbers: IZN-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No