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)
- Conditions
- moderate-to-severe axial spondyloarthritisMedDRA version: 20.0Level: PTClassification code 10071400Term: Axial spondyloarthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disordersTherapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- EUCTR2018-000176-15-GB
- Lead Sponsor
- Izana Bioscience Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 42
1. Age = 18 and = 75 years of age.
2. Diagnosis of axSpA by an appropriately qualified physician and classified using ASAS criteria = 3 months prior to Baseline; symptoms must have started before age 45.
3. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score = 4 and spinal pain score = 40, at screening and Baseline.
4. MRI evidence of active axSpA = 6 (ideally = 3) months prior to randomisation using ASAS criteria.
5. A negative tuberculosis (TB) screening assessment.
6. A female subject of childbearing potential who is sexually active with a nonsterilised male partner agrees to routinely use adequate contraception from signing of the informed consent throughout the duration of the study until the end of the safety follow up (18 weeks after last dose) (see Appendix 7 of protocol).
7. A male subject who is non-sterilised and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of the informed consent throughout the duration of the study until the end of the safety follow up (18 weeks after last dose) (see (see Appendix 7 of protocol).
8. Stable NSAID use for 28 days prior to study entry.
9. Stable use of MTX (= 25 mg/week), sulfasalazine (= 3 g/day) and leflunomide (= 20 mg/day) for 28 days prior to study entry.
10. Stable oral corticosteroid dose = 10 mg for 28 days prior to study entry.
11. Capable of giving signed informed consent as described in Appendix 2, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
In addition, the following inclusion criteria will apply for some subjects:
12. Inadequately responded to or experienced intolerance to previous treatment with an anti-TNF agent (limited to 50% of the total study population).
Note: Criteria for inadequate response to or experienced intolerance to previous treatment with an anti-TNF agent are defined as:
•Signs and symptoms of persistently active disease despite a history of at least one 12 week regimen of one of the following agents:
?Infliximab: 5 mg/kg i.v.
?Etanercept: 50 mg weekly
?Adalimumab: 40 mg fortnightly
?Golimumab: 50 mg monthly
?Certolizumab pegol: 400 mg SC initially and at weeks 2 and 4, followed by 200 mg every 2 weeks or 400 mg every 4 weeks
OR
•Recurrence of symptoms during scheduled maintenance dosing following prior clinical benefit (discontinuation despite clinical benefit does not qualify).
OR
•History of intolerance of at least one TNF antagonist (including, but not limited to infusion-related reaction, demyelination, congestive heart failure and infection).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 42
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. A current diagnosis of axSpA with a BASDAI > 4 but no evidence of inflammation on MRI.
2. Discontinued biologic therapy such as adalimumab, etanercept, infliximab, golimumab and certolizumab pegol < 8 weeks prior to Baseline.
3. Previous or current use oral corticosteroid and meets one of the following criteria:
•Is receiving prednisone or prednisone equivalent > 10 mg/day at Baseline;
•Has discontinued use of corticosteroid within 28 days of Baseline;
•Has not been on stable doses of corticosteroid for at least 28 days prior to Baseline; or
•Has been taking both oral budesonide and prednisone (or equivalent) simultaneously.
4. Received intra-articular or i.v. corticosteroids within 14 days prior to Screening or during the Screening Period.
5. Received anti-IL-17A or anti IL12/23 therapy.
6. Received cyclosporine, tacrolimus or mycophenolate mofetil within 28 days prior to Baseline.
7. Previously received stem cell transplantation.
8. Infection(s) requiring treatment with i.v. anti-infectives within 28 days prior to the Baseline Visit or oral anti-infectives within 14 days prior to the Baseline Visit.
9. Screening laboratory and other analyses show any of the following abnormal results:
•Serum AST or ALT > 1.5 × upper limit of normal (ULN); if bilirubin > ULN, then AST and ALT will be rechecked, and if > 1.5 × ULN, subject will be excluded;
•Estimated glomerular filtration rate < 40 mL/min/1.73 m2;
•Total white blood cell (WBC) count < 3,000/µL;
•Absolute neutrophil count (ANC) < 1,000/µL;
•Platelet count < 100,000/µL;
•Absolute lymphocyte count < 750/µL;
•Haemoglobin < 9 g/dL.
10. Any active or recurrent viral infection that based on the Investigator's clinical assessment makes the subject an unsuitable candidate for the study, including recurrent/disseminated herpes zoster or known history of human immunodeficiency virus (HIV).
11. Hepatitis B (hepatitis B virus surface antigen [HBsAg] positive [+] or detected sensitivity on the hepatitis B virus [HBV] DNA polymerase chain reaction [PCR] qualitative test for hepatitis B core antibodies [HBc Ab]/hepatitis B surface antibody [HBsAb] positive subjects) or hepatitis C (hepatitis C virus [HCV] RNA detectable in any subject with anti-hepatitis C virus antibody [HCV Ab]).
12. Any active or chronic recurring infections or untreated latent TB.
13. History of moderate-to-severe congestive heart failure (New York Heart Association [NYHA] class III or IV), risk factors for coronary syndrome, hypertension, angina and myocardial infarction, cerebrovascular accident and any other condition within 6 months, which in the opinion of the Investigator, would put the subject at risk by participation in the study.
14. Receipt of any live vaccine within 2 weeks prior to randomisation, or will require live vaccination during study participation including up to 1 month after the last dose of study drug.
15. Evidence of current or prior dysplasia or history of malignancy (including of the gastrointestinal tract) other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localised carcinoma in situ of the cervix or adenomatous polyp that has been completely resected.
16. Has had any uncontrolled and/or clinically significant (per Investigator's judgement) illness, hospitalisation, or has had any surgical procedure requiring general anaesthesia within 30 days prior to Screening, or has any planned surgical procedure withi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the efficacy of namilumab 150 mg subcutaneous (sc), given on weeks 0, 2, 6 and 10 in subjects with axSpA;Secondary Objective: To assess the efficacy of namilumab 150 mg sc, given on weeks 0, 2, 6 and 10 on other clinical responses in subjects with axSpA<br>To assess the safety and tolerability of namilumab 150 mg sc, given on weeks 0, 2, 6 and 10 in subjects with axial spondyloarthritis;Primary end point(s): Proportion of subjects who achieve an ASAS20 clinical response at week 12;Timepoint(s) of evaluation of this end point: week 12
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Proportion of subjects who achieve ASAS40 and ASAS70 response at week 12<br>2. Proportion of subjects who achieve an ASAS20 clinical response at week 6<br>3. Proportion of subjects who achieve ASDAS-CRP response at weeks 6 and 12<br>;Timepoint(s) of evaluation of this end point: 1. week 12<br>2. week 6<br>3. weeks 6 and 12