Natrunix in HLA-B27 Positive Subjects With Axial Spondyloarthritis
NCT Number: NCT06526377
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Axial Spondyloarthritis
Interventions: DRUG: Natrunix|DRUG: Placebo
Sponsor: XBiotech, Inc.
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 60
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-08-15
Completion Date: 2025-04-30

Summary:
Double-blind, placebo-controlled, randomized trial of Natrunix in combination with Standard of Care in patients with Axial Spondyloarthritis

Primary Outcome Measures: Assessment of Spondyloarthritis International Society (ASAS) criteria will be used to determine proportion of subjects achieving 40% Improvement (ASAS40 response), In this study, sponsor will assess the safety and effectiveness of Natrunix (human antibody preparation) in combination with Standard of Care to determine the ASAS40 response rate. ASAS response is the measure of improvement in percentage of Axial Spondyloarthritis (AxSpA) disease. Patients who achieved at least 40% improvement on Assessment of Spondyloarthritis International Society (ASAS40) at week 12 will be considered as an ASAS40 responder for the primary analysis., At 12 weeks from Baseline
Secondary Outcome Measures: Improvement/Deterioration in Patient's Global Assessment of Disease (PGA) Activity (using Numerical Rating Scale (NRS)), A patient global assessment of Disease (PGA) will be administered to assess your overall treatment response and disease status in AxSpa. Subjects will be evaluated to estimate disease activity on a 0-10 scale where 10 is maximum worsening., At 12 weeks from Baseline|Pain assessment (using Numerical Rating Scale (NRS)), Numerical Rating Scale for Pain (NRS) diary will be given to rate subject's pain from 0-10 (no pain to highest pain) for average pain and worst pain in past 24 hours., At 12 weeks from Baseline|Improvement/Deterioration in Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), The Bath Ankylosing Spondylitis Functional Index (BASFI) will be administered to assess the degree of subject's functional limitation. Questionnaires will ask the subjects the rate difficulty in daily activity on 0-10 scale where 0 is easy and 10 is impossible., At 12 weeks from Baseline|Improvement/Deterioration in inflammation (mean of questions 5 and 6 on the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) will be administered to access subject's AxSpa. It to evaluate symptoms such as spinal pain, joint pain, morning stiffness duration/ severity, fatigue, and discomfort experienced. These symptoms will be assessed on scale of 0-10 where 0 is none and 10 is very severe., At 12 weeks
Other Outcome Measures: ASAS40 response, ASAS response criteria consist of 4 domains that are of importance in assessing the improvement in signs and symptoms of patients with AS. These measures focus on AS disease activity, physical function, total spinal pain, and spinal stiffness/inflammation. ASAS40 indicates a ≥40% improvement in 3 of the 4 below domains and no worsening of 20% in the remaining domain.

ASAS response criteria include improvements in each of the 4 domains: BASFI (Bath Ankylosing Spondylitis Functional Index) Patient Global Assessment of Disease Activity Total Spinal Pain Inflammation (Morning Stiffness), At Weeks 1, 3, 5, 8 and 10 from Baseline|ASAS20 response, ASAS response criteria consist of 4 domains that are of importance in assessing the improvement in signs and symptoms of patients with AS. These measures focus on AS disease activity, physical function, total spinal pain, and spinal stiffness/inflammation.

ASAS20 indicates a ≥20% improvement in 3 of the 4 below domains and no worsening of 20% in the remaining domain.

ASAS response criteria include improvements in each of the 4 domains: BASFI (Bath Ankylosing Spondylitis Functional Index) Patient Global Assessment of Disease Activity Total Spinal Pain Inflammation (Morning Stiffness), At Weeks 1, 3, 5, 8, 10, and 12 from Baseline|ASAS50 response, ASAS response criteria consist of 4 domains that are of importance in assessing the improvement in signs and symptoms of patients with AS. These measures focus on AS disease activity, physical function, total spinal pain, and spinal stiffness/inflammation. ASAS50 indicates a ≥50% improvement in 3 of the 4 below domains and no worsening of 20% in the remaining domain.

ASAS response criteria include improvements in each of the 4 domains: BASFI (Bath Ankylosing Spondylitis Functional Index) Patient Global Assessment of Disease Activity Total Spinal Pain Inflammation (Morning Stiffness), At Weeks 1, 3, 5, 8, 10, and 12 from Baseline|ASAS70 response, ASAS response criteria consist of 4 domains that are of importance in assessing the improvement in signs and symptoms of patients with AS. These measures focus on AS disease activity, physical function, total spinal pain, and spinal stiffness/inflammation. ASAS70 indicates a ≥70% improvement in 3 of the 4 below domains and no worsening of 20% in the remaining domain.

ASAS response criteria include improvements in each of the 4 domains: BASFI (Bath Ankylosing Spondylitis Functional Index) Patient Global Assessment of Disease Activity Total Spinal Pain Inflammation (Morning Stiffness), At Weeks 1, 3, 5, 8, 10, and 12 from Baseline|Improvement/deterioration in Patient's Global Assessment (PGA) of Disease Activity (using Numerical Rating scale (NRS)) both average and worst, A patient global assessment of Disease (PGA) will be administered to assess your overall treatment response and disease status in AxSpa. Subjects will be evaluated to estimate disease activity on a 0-10 scale where 10 is maximum worsening. Numerical Rating Scale for Pain (NRS) diary will be given to rate subject's pain from 0-10 (no pain to highest pain) for average pain and worst pain in past 24 hours., At Weeks 1, 3, 5, 8 and 10 from Baseline|Pain Assessment (using Numerical Rating Scale (NRS)) both average and worst, Numerical Rating Scale for Pain (NRS) diary will be given to rate subject's pain from 0-10 (no pain to highest pain) for average pain and worst pain in past 24 hours., At Weeks 1, 3, 5, 8 and 10 from Baseline|Improvement/deterioration in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) will be administered to access subject's AxSpa. It to evaluate symptoms such as spinal pain, joint pain, morning stiffness duration/ severity, fatigue, and discomfort experienced. These symptoms will be assessed on scale of 0-10 where 0 is none and 10 is very severe., At Weeks 1, 3, 5, 8, 10, and 12 from Baseline|Improvement/deterioration in Bath Ankylosing Spondylitis Functional Index (BASFI), The Bath Ankylosing Spondylitis Functional Index (BASFI) will be administered to assess the degree of subject's functional limitation. Questionnaires will ask the subjects the rate difficulty in daily activity on 0-10 scale where 0 is easy and 10 is impossible., At Weeks 1, 3, 5, 8 and 10 from Baseline|Improvement/deterioration in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), The enthesitis evaluation is performed based on 7 assessments:

1. 1st costochondral joint left and right,
2. 7th costochondral joint (left/right (LR)),
3. posterior superior iliac spine LR,
4. anterior superior iliac spine LR,
5. iliac crest LR,
6. 5th lumbar spinous process and
7. proximal insertion of Achilles tendon left and right. Each anatomic site is graded for presence (1) or absence (0) of pain/tenderness. Total MASES score therefore ranges from 0 (0 sites with tenderness) to 13 (worst possible score; 13 sites with tenderness)., At Weeks 1, 3, 5, 8, 10, and 12 from Baseline|Improvement/Deterioration in Tender Joint Count (TJC), Tender Joint Count (TJC) will be used to assess the tenderness of your joints., At Weeks 1, 3, 5, 8, 10, and 12 from Baseline|Improvement/Deterioration in Swollen Joint Count (SJC), Swollen Joint Count (SJC) will be used to assess the swelling of your joints., At Week 1, 3, 5, 8, 10, and 12 from Baseline|Study Emergent Anterior Uveitis (AU), The study emergent events of Anterior Uveitis will be documented and monitored in the study., At Weeks 0, 5 and 12 from Baseline|Improvement/Deterioration of Anterior Uveitis symptoms using Ocular Pain Assessment Survey (OPAS), The OPAS is a patient reported survey assessing eye pain location, eye pain intensity over the prior 24 hours and 2 weeks, eye pain impact on quality of life, eye pain aggravating/alleviating factors, eye pain associated factors, and associated non-eye pain intensity. Subjects will document the location of any eye pain on a diagram of the face and eyes, and the remaining questions will be answered utilizing either a 0-10 or 0%-100% scale as appropriate., At 1, 3, 5, 8, 10, and 12 from Baseline|Improvement/Deterioration of Ankylosing Spondylitis Quality of Life (ASQoL), Ankylosing Spondylitis Quality of Life (ASQoL) is a valuable tool to access your quality of life living with ankylosing spondylitis. This includes answering 'Yes' or 'No' to the questions., At Weeks 1, 3, 5, 8, 10, and 12. from Baseline|Evaluator's (Physician's) Global Assessment of Disease (EGA), Evaluator's (Physician's) Global Assessment of Disease (EGA) will be administered to the subject by investigator to assess overall treatment response and disease status in AxSpA. It will be evaluated to estimate disease activity on a 0-10 scale where 10 is maximum worsening., At Weeks 1, 3, 5, 8, 10, and 12 from Baseline|Improvement/Deterioration in response of Health Assessment Questionnaire Disability Index (HAQ-DI), Degree of disability was self-evaluated by participant using HAQ-DI.Assessment was made based on activities capable without any aids/devices. 20-question instrument assessed degree of difficulty person had in accomplishing tasks in 8 functional areas(dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0(indicated no difficulty)to 3(indicated inability to perform task in that area). Overall score computed as: sum of domain scores and divided by number of domains answered. Total possible score range:0-3 where 0=least difficulty and 3=extreme difficulty., At Weeks 1, 3, 5, 8, 10, and 12 from Baseline|Improvement/Deterioration in inflammation (mean of questions 5 and 6 on the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) will be administered to access subject's AxSpa. It to evaluate symptoms such as spinal pain, joint pain, morning stiffness duration/ severity, fatigue, and discomfort experienced. These symptoms will be assessed on scale of 0-10 where 0 is none and 10 is very severe., At Weeks 1, 3, 5, 8 and 10 from Baseline|Number of subjects with increased dosage/new SOC medications, Number of subjects with increased dosage/new SOC medications will be compared between the treatment arms., At Weeks 3, 8 and 12 from Baseline|Number of subjects with reduced/discontinued SOC medications, Number of subjects with reduced/discontinued SOC medications will be compared between the treatment arms., At Weeks 3, 8 and 12 from Baseline|AEs and SAEs, All subjects who received study drug will be included in safety analysis. Safety analysis will be based on adverse events, vital signs, physical examinations, and clinical laboratory measurements. Adverse events will be grouped by System Organ Class (SOC) and Preferred Term (PT) within SOC according to the latest MedDRA coding dictionary., 7 days from last dose|Number of Participants with Clinically Significant Changes in Physical Examination Findings using the Physical Exam Assessment during the course of the study, Parameters assessed are below:

General Appearance Head Eyes Ears Nose Mouth Throat Neck Lymph Nodes Pulmonary Cardiovascular Abdomen Skin Musculoskeletal Neurological, up to 24 weeks|Number of Participants with Clinically Significant Changes in Vital Signs during the course of the study, Parameters assessed are below:

Systolic Blood Pressure Diastolic Blood Pressure Pulse Body Temperature Peripheral Blood Oxygen Saturation Respiratory Rate, up to 24 weeks|Number of participants with clinically significant abnormal value in laboratory test results which represent a change from pre-study values during the course of the study, Parameters assessed are below:

Chemistry panel: Analysis to evaluate if you are in generally good health. Your body's electrolyte balance and the status/function of some of your internal organ systems will be assessed.

Hematology Panel: Analysis to evaluate the levels of different types of blood cells present in your blood.

Urinalysis: Subject's urine will be collected to analyze pH, protein, glucose, and blood cells (RBCs and WBCs)., up to 24 weeks|ASAS40 response, ASAS response criteria consist of 4 domains that are of importance in assessing the improvement in signs and symptoms of patients with AS. These measures focus on AS disease activity, physical function, total spinal pain, and spinal stiffness/inflammation. ASAS40 indicates a ≥40% improvement in 3 of the 4 below domains and no worsening of 20% in the remaining domain.

ASAS response criteria include improvements in each of the 4 domains: BASFI (Bath Ankylosing Spondylitis Functional Index) Patient Global Assessment of Disease Activity Total Spinal Pain Inflammation (Morning Stiffness), At OLE weeks 17 and 24 from Baseline|ASAS20 response, ASAS response criteria consist of 4 domains that are of importance in assessing the improvement in signs and symptoms of patients with AS. These measures focus on AS disease activity, physical function, total spinal pain, and spinal stiffness/inflammation. ASAS20 indicates a ≥20% improvement in 3 of the 4 below domains and no worsening of 20% in the remaining domain.

ASAS response criteria include improvements in each of the 4 domains: BASFI (Bath Ankylosing Spondylitis Functional Index) Patient Global Assessment of Disease Activity Total Spinal Pain Inflammation (Morning Stiffness), At OLE weeks 17 and 24 from Baseline|ASAS50 response, ASAS response criteria consist of 4 domains that are of importance in assessing the improvement in signs and symptoms of patients with AS. These measures focus on AS disease activity, physical function, total spinal pain, and spinal stiffness/inflammation. ASAS50 indicates a ≥50% improvement in 3 of the 4 below domains and no worsening of 20% in the remaining domain.

ASAS response criteria include improvements in each of the 4 domains: BASFI (Bath Ankylosing Spondylitis Functional Index) Patient Global Assessment of Disease Activity Total Spinal Pain Inflammation (Morning Stiffness), At OLE weeks 17 and 24 from Baseline|ASAS70 response, ASAS response criteria consist of 4 domains that are of importance in assessing the improvement in signs and symptoms of patients with AS. These measures focus on AS disease activity, physical function, total spinal pain, and spinal stiffness/inflammation. ASAS70 indicates a ≥70% improvement in 3 of the 4 below domains and no worsening of 20% in the remaining domain.

ASAS response criteria include improvements in each of the 4 domains: BASFI (Bath Ankylosing Spondylitis Functional Index) Patient Global Assessment of Disease Activity Total Spinal Pain Inflammation (Morning Stiffness), At OLE weeks 17 and 24 from Baseline|Patient's Global Assessment of Disease Activity (using Numerical Rating Scale (NRS)) both average and worst, A patient global assessment of Disease (using Numerical Rating Scale (NRS)) will be administered to assess your overall treatment response and disease status in AxSpa. Subjects will be evaluated to estimate disease activity on a 0-10 scale where 10 is maximum worsening., At OLE weeks 17 and 24 from Baseline|Pain Assessment (using Numerical Rating Scale (NRS)) both average and worst, Numerical Rating Scale for Pain (NRS) diary will be given to rate subject's pain from 0-10 (no pain to highest pain) for average pain and worst pain in past 24 hours., At OLE weeks 17 and 24 from Baseline|Improvement/Deterioration in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) will be administered to access subject's AxSpa. It to evaluate symptoms such as spinal pain, joint pain, morning stiffness duration/ severity, fatigue, and discomfort experienced. These symptoms will be assessed on scale of 0-10 where 0 is none and 10 is very severe., At OLE weeks 17 and 24 from Baseline|Improvement/Deterioration in Bath Ankylosing Spondylitis Functional Index (BASFI), The Bath Ankylosing Spondylitis Functional Index (BASFI) will be administered to assess the degree of subject's functional limitation. Questionnaires will ask the subjects the rate difficulty in daily activity on 0-10 scale where 0 is easy and 10 is impossible., At OLE weeks 17 and 24 from Baseline|Improvement/Deterioration in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), The enthesitis evaluation is performed based on 7 assessments:

1. 1st costochondral joint left and right,
2. 7th costochondral joint (left/right (LR)),
3. posterior superior iliac spine LR,
4. anterior superior iliac spine LR,
5. iliac crest LR,
6. 5th lumbar spinous process and
7. proximal insertion of Achilles tendon left and right. Each anatomic site is graded for presence (1) or absence (0) of pain/tenderness. Total MASES score therefore ranges from 0 (0 sites with tenderness) to 13 (worst possible score; 13 sites with tenderness)., At OLE weeks 17 and 24 from Baseline|Improvement/Deterioration in Tender Joint Count (TJC), Tender Joint Count (TJC) will be used to assess the tenderness of your joints., At OLE weeks 17 and 24 from Baseline|Improvement/Deterioration in Swollen Joint Count (SJC), Swollen Joint Count (SJC) will be used to assess the swelling of your joints., At OLE weeks 17 and 24 from Baseline|Study Emergent Anterior Uveitis (AU), The study emergent events of Anterior Uveitis will be documented and monitored in the study., At OLE weeks 17 and 24 from Baseline|Improvement/Deterioration of Anterior Uveitis symptoms using Ocular Pain Assessment Survey (OPAS), The OPAS is a patient reported survey assessing eye pain location, eye pain intensity over the prior 24 hours and 2 weeks, eye pain impact on quality of life, eye pain aggravating/alleviating factors, eye pain associated factors, and associated non-eye pain intensity. Subjects will document the location of any eye pain on a diagram of the face and eyes, and the remaining questions will be answered utilizing either a 0-10 or 0%-100% scale as appropriate., At OLE weeks 17 and 24 from Baseline|Improvement/Deterioration in Ankylosing Spondylitis Quality of Life (ASQoL), Ankylosing Spondylitis Quality of Life (ASQoL) is a valuable tool to access your quality of life living with ankylosing spondylitis. This includes answering 'Yes' or 'No' to the questions., At OLE weeks 17 and 24 from Baseline|Evaluator's (Physician's) Global Assessment of Disease (EGA), Evaluator's (Physician's) Global Assessment of Disease (EGA) will be administered to the subject by investigator to assess overall treatment response and disease status in AxSpa. It will be evaluated to estimate disease activity on a 0-10 scale where 10 is maximum worsening., At OLE weeks 17 and 24 from Baseline|Improvement/Deterioration in response of Health Assessment Questionnaire Disability Index (HAQ-DI), Degree of disability was self-evaluated by participant using HAQ-DI. Assessment was made based on activities capable without any aids/devices. 20-question instrument assessed degree of difficulty person had in accomplishing tasks in 8 functional areas(dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0(indicated no difficulty) to 3(indicated inability to perform task in that area). Overall score computed as: sum of domain scores and divided by number of domains answered. Total possible score range:0-3 where 0=least difficulty and 3=extreme difficulty., At OLE weeks 17 and 24 from Baseline|Improvement/Deterioration in inflammation (mean of questions 5 and 6 on the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) will be administered to access subject's AxSpa. It to evaluate symptoms such as spinal pain, joint pain, morning stiffness duration/ severity, fatigue, and discomfort experienced. These symptoms will be assessed on scale of 0-10 where 0 is none and 10 is very severe., At OLE weeks 17 and 24 from Baseline|Number of subjects with increased dosage/new SOC medications, Number of subjects with increased dosage/new SOC medications will be compared between treatment arms., At OLE weeks 17 and 24 from Baseline|Number of subjects with reduced/discontinued SOC medications, Number of subjects with reduced/discontinued SOC medications will be compared between treatment arms., At weeks 17 and 24 from Baseline