Axial Spondyloarthritis
Conditions
Brief summary
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.
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).
Interventions
BIOLOGICALPlacebo
Placebo solution for subcutaneous injection.
BIOLOGICALNamilumab
Namilumab solution for subcutaneous injection
Sponsors
Iqvia Pty Ltd
Innovate UK
Izana Bioscience Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Subjects Who Achieved ASAS20 Clinical Response | Weeks 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Who Achieved ASAS40 Clinical Response at Week 12 | Week 12 | Proportion of subjects who achieved Assessment in Ankylosing Spondylitis with 40% improvement (ASAS40) response at Week 12 |
| Proportion of Subjects Who Achieved an ASAS20 Clinical Response at Week 6 | Week 6 | Proportion of subjects who achieved an ASAS20 clinical response at Week 6 |
| Proportion of Subjects Who Achieved Ankylosing Spondylitis Disease Activity Score C-reactive Protein (ASDAS-CRP) Response at Weeks 6 | Week 6 | Proportion (percentage) of subjects who achieved Ankylosing Spondylitis Disease Activity Score C-reactive Protein (ASDAS-CRP) response at Week 6, Clinically Important Improvement |
| Proportion of Subjects Who Achieved Clinically Important ASDAS-CRP Score at Week 12 | Week 12 | Proportion of Subjects Who Achieved Clinically Important ASDAS-CRP Score at Week 12, Clinically Important Improvement |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo solution administered by subcutaneous injection on 4 occasions over 10 weeks
Placebo: Placebo solution for subcutaneous injection. | 6 |
| Namilumab Namilumab (150 mg) administered by subcutaneous injection on 4 occasions over 10 weeks
Namilumab: Namilumab solution for subcutaneous injection | 36 |
| Total | 42 |
Baseline characteristics
| Characteristic | Placebo | Namilumab | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 35 Participants | 41 Participants |
| BMI | 27.85 kg/m^2 | 27.6 kg/m^2 | 27.65 kg/m^2 |
| Duration of disease <2years | 4 participants | 16 participants | 20 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 33 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Height | 175.5 cm | 173.5 cm | 174.5 cm |
| Prior use of anti-tumor necrosis factor (TNF) treatment | 1 participants | 6 participants | 7 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 34 Participants | 39 Participants |
| Region of Enrollment United Kingdom | 6 Participants | 36 Participants | 42 Participants |
| Sex: Female, Male Female | 2 Participants | 15 Participants | 17 Participants |
| Sex: Female, Male Male | 4 Participants | 21 Participants | 25 Participants |
| Weight | 86.5 kg | 80.5 kg | 82.15 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 36 |
| other Total, other adverse events | 5 / 6 | 31 / 36 |
| serious Total, serious adverse events | 0 / 6 | 1 / 36 |
Outcome results
Primary
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.
Time frame: Weeks 12
Population: Full Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | The Proportion of Subjects Who Achieved ASAS20 Clinical Response | 3 Participants |
| Namilumab | The Proportion of Subjects Who Achieved ASAS20 Clinical Response | 14 Participants |
Secondary
Proportion of Subjects Who Achieved an ASAS20 Clinical Response at Week 6
Proportion of subjects who achieved an ASAS20 clinical response at Week 6
Time frame: Week 6
Population: Full Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Proportion of Subjects Who Achieved an ASAS20 Clinical Response at Week 6 | 0 Participants |
| Namilumab | Proportion of Subjects Who Achieved an ASAS20 Clinical Response at Week 6 | 12 Participants |
Secondary
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
Time frame: Week 6
Population: Full Analysis Set. Overall number of participants analyzed reflect those with available ASDAS-CRP Scores as reported in the final clinical study report.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Proportion of Subjects Who Achieved Ankylosing Spondylitis Disease Activity Score C-reactive Protein (ASDAS-CRP) Response at Weeks 6 | 0 Participants |
| Namilumab | Proportion of Subjects Who Achieved Ankylosing Spondylitis Disease Activity Score C-reactive Protein (ASDAS-CRP) Response at Weeks 6 | 10 Participants |
Secondary
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
Time frame: Week 12
Population: Full Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Proportion of Subjects Who Achieved ASAS40 Clinical Response at Week 12 | 3 Participants |
| Namilumab | Proportion of Subjects Who Achieved ASAS40 Clinical Response at Week 12 | 9 Participants |
Secondary
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
Time frame: Week 12
Population: Full Analysis Set. Overall number of participants analyzed reflect those with available ASDAS-CRP Scores as reported in the final clinical study report.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Proportion of Subjects Who Achieved Clinically Important ASDAS-CRP Score at Week 12 | 1 Participants |
| Namilumab | Proportion of Subjects Who Achieved Clinically Important ASDAS-CRP Score at Week 12 | 10 Participants |