Usability of an AI for M923 in Subjects With Moderate to Severe RA

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the usability of an auto-injector (AI) for the delivery of M923 in patients with rheumatoid arthritis (RA)

Official Title
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An Open-label Single-arm Multicenter Study to Evaluate Usability of a Subcutaneous (SC) Autoinjector (AI) for a Proposed Adalimumab Biosimilar (M923) in Subjects With Moderate to Severe Rheumatoid Arthritis (RA)

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: M923
* Device: Autoinjector


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants ≥18 years old at the time of Screening Able to understand and communicate with the Investigator and comply with the requirements of the study, and must give a written, signed and dated informed consent before any study related activity is performed. Where relevant, a legal representative will also sign the informed study consent according to local laws and regulations. RA diagnosed for at least 6 months before Screening Meets classification criteria for rheumatoid arthritis (RA) by 2010 American College of Rheumatology/European League Against Rheumatism criteria Active disease at Screening and Baseline Participants must have at least 1 documented swollen and/or tender joint in their hand or wrist of the dominant hand as assessed by the Investigator or designated assessor Must be willing and able to attempt self-administration of subcutaneous (SC) injection(s) Male participants and their female partners must be willing to comply with the contraception restrictions for this study from the time of the first administration of investigational product (IP) until 3 months after the last dose. Female participants must have a negative pregnancy test at screening and on admission to the clinic, and must not be lactating and must be using an acceptable method of contraception throughout the study and for 3 months after the last dose, or be of non-childbearing potential. Non-pregnant female partners of male participants who are of childbearing potential should use an effective form of contraception. Exclusion Criteria: Prior use of systemic tumor necrosis factor (TNF) inhibitor therapy. Prior use of rituximab Prior use of abatacept, tocilizumab and tofacitinib within 4 weeks prior to Screening Current use of a conventional disease modifying anti-rheumatic drugs (DMARD) other than the following: methotrexate orally (≤25 mg/day), hydroxychloroquine (≤400 mg/day) or sulfasalazine (≤3 g/day)) at a stable dose for at least 4 weeks prior to Screening. If discontinued, methotrexate, hydroxychloroquine, and sulfasalazine must have been discontinued at least 4 weeks prior to Baseline. No other conventional DMARDs are permitted and no combination therapy is permitted. Prior use of cytotoxic or alkylating agents or immunosuppressants must have been discontinued for at least 90 days prior to Baseline Current use of oral corticosteroids at a dose >10 mg/day prednisone or equivalent or change of dose within 2 weeks prior to Screening Current use of more than 1 nonsteroidal anti-inflammatory drug. Prior use of injectable corticosteroids (intramuscular [IM], intra-articular [IA], or intravenous [IV]) within 6 weeks prior to Baseline Prior or current use of other self-injected drugs, eg, insulin All other prior non-RA concomitant treatments must be on a stable dose for at least 4 weeks before Baseline Meets Class IV Steinbrocker criteria for disability/activities of daily living Laboratory abnormalities at Screening deemed clinically significant by the Investigator and/or Sponsor. Presence of fibromyalgia, another autoimmune rheumatologic illness or inflammatory arthritis, eg, systemic lupus erythematosus, gout. The presence of secondary Sjogren's syndrome is permitted. Joint surgery within the last 8 weeks prior to Screening Severe, progressive, or uncontrolled renal, hepatic, metabolic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac or neurologic disease, including pleural effusions or ascites, which in the opinion of the Investigator would preclude the participant from adhering to or completing the study or where participation in the study exposes the participant to unfavorable benefit/risk History or presence of signs and/or symptoms or a diagnosis of a demyelinating disorder History or presence of Class III or IV New York Heart Association congestive heart failure History or presence of symptoms suggestive of lymphoproliferative disorders, lymphoma, leukemia, myeloproliferative disorders, or multiple myeloma Existing malignancy or history of any malignancy except adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ, with no more than 3 lifetime basal cell or squamous cell carcinomas Chronic infections, recurrent infections (3 or more of the same infection requiring anti-infective treatment in any rolling 12-month period); any recent infection (ie, in the last 30 days) requiring hospitalization or any infection requiring parenteral anti-infective therapy within 30 days or oral infective therapies within 14 days of Baseline; herpes zoster within 6 months of Baseline or more than 2 lifetime episodes of herpes zoster; or history of systemic fungal infection or opportunistic infection (eg, coccidioidomycosis, histoplasmosis, toxoplasmosis) History or presence of human immunodeficiency virus (HIV), Hepatitis B or C virus History of active tuberculosis (TB) or untreated or inadequately treated latent TB. Participant has been exposed to an investigational product (IP) within 30 days (or 5 half-lives) prior to enrollment, whichever is longer, or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study Participant is a family member or employee of the Investigator or Baxalta or its partners

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All Study Participants<br>All study participants to receive M923 administered via a subcutaneous auto-injector (AI) | Biological: M923<br>* Recombinant human immunoglobulin G subclass 1 (IgG1) monoclonal antibody specific for human tumor necrosis factor-alpha (TNF-α)<br>* Other names: Adalimumab;Device: Autoinjector<br>* Subcutaneous administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Usability of the Auto-injector (AI) at Week 4 | The primary usability measure was the participant rating captured in the PRE- and POST-Self-injection Assessment Questionnaire (SIAQ) modules at Week 4. The PRE-SIAQ module is a 7-item questionnaire that investigates feelings about injections, self-confidence (regarding self-administration), and satisfaction with self-injection. The POST-SIAQ module is a 27-item questionnaire that assesses feelings about injections, self-image, self-confidence (regarding self-administration), pain and skin reactions during or after injection (injection-site reactions), ease of use of the self-injection device, and satisfaction with self-injection. Participants rated each item of the SIAQ on a 5-point (or 6-point) semantic Likert-type scale, where a score of 1 corresponds to a participant's worst experience and a score of 5 (or 6) corresponds to a participant's best experience. Item scores were transformed to obtain a score ranging from 0 (worst experience) to 10 (best experience) for each item. | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Successful Injections as Assessed by the Observer at Week 4 | Observers assessed usability by using a self-injection checklist. Self-injection assessment was coded as successful if categories P7 (removed protective needle cap from auto-injector), P10 (press down on auto-injector to insert the needle into the skin), and P11 (held auto-injector pressed fully down through second click sound) were checked as yes. | Week 4 | 
| Number of Participants With Hazard-free Injections as Assessed by the Observer at Week 4 | Observers assessed usability by using a potential hazard checklist. If all potential hazards in the checklist were checked as no, the assessment was coded as hazard free. | Week 4 | 
| Usability of the Auto-injector at Baseline | The usability measure was the participant rating captured in the PRE- and POST- SIAQ modules at Baseline. The PRE-SIAQ module is a 7-item questionnaire that investigates feelings about injections, self-confidence (regarding self-administration), and satisfaction with self-injection. The POST-SIAQ module is a 27-item questionnaire that assesses feelings about injections, self-image, self-confidence (regarding self-administration), pain and skin reactions during or after injection (injection-site reactions), ease of use of the self-injection device, and satisfaction with self-injection. Participants rated each item of the SIAQ on a 5-point (or 6-point) semantic Likert-type scale, where a score of 1 corresponds to a participant's worst experience and a score of 5 (or 6) corresponds to a participant's best experience. Item scores were transformed to obtain a score ranging from 0 (worst experience) to 10 (best experience) for each item. | Baseline (Day 1) | 
| Usability of the Auto-injector at Week 2 | The usability measure was the participant rating captured in the PRE- and POST- SIAQ modules at Week 2. The PRE-SIAQ module is a 7-item questionnaire that investigates feelings about injections, self-confidence (regarding self-administration), and satisfaction with self-injection. The POST-SIAQ module is a 27-item questionnaire that assesses feelings about injections, self-image, self-confidence (regarding self-administration), pain and skin reactions during or after injection (injection-site reactions), ease of use of the self-injection device, and satisfaction with self-injection. Participants rated each item of the SIAQ on a 5-point (or 6-point) semantic Likert-type scale, where a score of 1 corresponds to a participant's worst experience and a score of 5 (or 6) corresponds to a participant's best experience. Item scores were transformed to obtain a score ranging from 0 (worst experience) to 10 (best experience) for each item. | Week 2 | 
| Number of Participants With Successful Injections as Assessed by the Observer at Baseline | Observers assessed usability by using a self-injection checklist. Self-injection assessment was coded as successful if categories P7 (removed protective needle cap from auto-injector), P10 (press down on auto-injector to insert the needle into the skin), and P11 (held auto-injector pressed fully down through second click sound) were checked as yes. | Baseline (Day 1) | 
| Number of Participants With Hazard-free Injections as Assessed by the Observer at Baseline | Observers assessed usability by using a potential hazard checklist. If all potential hazards in the checklist were checked as no, the assessment was coded as hazard free. | Baseline (Day 1) | 
| Number of Participants With Successful Injections as Assessed by the Observer at Week 2 | Observers assessed usability by using a self-injection checklist. Self-injection assessment was coded as successful if categories P7 (removed protective needle cap from auto-injector), P10 (press down on auto-injector to insert the needle into the skin), and P11 (held auto-injector pressed fully down through second click sound) were checked as yes. | Week 2 | 
| Number of Participants With Hazard-free Injections as Assessed by the Observer at Week 2 | Observers assessed usability by using a potential hazard checklist. If all potential hazards in the checklist were checked as no, the assessment was coded as hazard free. | Week 2 | 
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments | Hematology, clinical chemistry, and urinalysis clinical laboratory parameters were assessed. The hematology panel consisted of complete blood count, hemoglobin, hematocrit, mean cell volume, total leukocytes, and platelet counts. The clinical chemistry panel consisted of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, total bilirubin, lactate dehydrogenase, creatine kinase, C-reactive protein, cholesterol, triglycerides, total protein, sodium, potassium, chloride, blood urea nitrogen, creatinine, albumin, calcium, phosphate, glucose, glycosylated hemoglobin, uric acid, and bicarbonate. The urinalysis panel consisted of leucocytes, protein, bilirubin, urobilinogen, glucose, ketones, blood pH, nitrite, and specific gravity. Clinical significance was assessed by the Investigator. | Baseline; 32 Weeks | 
| Number of Participants With Vital Signs Outside the Expected Range | Vital signs included respiratory rate, body temperature, pulse rate, and systolic and diastolic blood pressure. | 32 Weeks | 
| Number of Participants With Clinically Significant Changes in Twelve-lead Electrocardiogram (ECG) Findings | Clinical significance was assessed by the Investigator. | Baseline; 32 Weeks | 
| Number of Participants With Adverse Events Leading to Premature Study Withdrawal | The number of participants who had an adverse event that led to premature study withdrawal was assessed. | 32 Weeks | 
| Number of Participants With Treatment-emergent Injection Site Reactions | An injection site reaction is defined as pain, tenderness, erythema/redness, induration/swelling, and other. If an injection site reaction was observed, a physician was to characterize and document the reaction as an adverse event (AE). Treatment-emergent adverse events (TEAEs) are defined as AEs that started or worsened in severity on or after the first dose of study medication, until study completion/withdrawal or within 30 days following the last treatment for early withdrawn participants. | 32 Weeks | 
| Immunogenicity of M923 Assessed as the Number of Participants With Evidence of Seroconversion as Measured by Titer of Anti-drug Antibodies (ADAs) at Baseline | A participant was considered to have developed ADAs if a confirmed positive result was observed at any time during the treatment period post-dose (irrespective of titer value). Samples were collected predose (prior to administering investigational product) and before any hematology/chemistry samples were drawn at that visit. | Baseline (Day 1) | 
| Immunogenicity of M923 Assessed as the Number of Participants With Evidence of Seroconversion as Measured by Titer of ADAs at Week 4 | A participant was considered to have developed ADAs if a confirmed positive result was observed at any time during the treatment period post-dose (irrespective of titer value). Samples were collected predose (prior to administering investigational product) and before any hematology/chemistry samples were drawn at that visit. | Week 4 | 
| Immunogenicity of M923 Assessed as the Number of Participants With Evidence of Seroconversion as Measured by Titer of ADAs at Week 12 | A participant was considered to have developed ADAs if a confirmed positive result was observed at any time during the treatment period post-dose (irrespective of titer value). Samples were collected predose (prior to administering investigational product) and before any hematology/chemistry samples were drawn at that visit. | Week 12 | 
| Immunogenicity of M923 Assessed as the Number of Participants With Evidence of Seroconversion as Measured by Titer of ADAs at Week 24 | A participant was considered to have developed ADAs if a confirmed positive result was observed at any time during the treatment period post-dose (irrespective of titer value). Samples were collected predose (prior to administering investigational product) and before any hematology/chemistry samples were drawn at that visit. | Week 24 | 
| Immunogenicity of M923 Assessed as the Number of Participants With Evidence of Seroconversion as Measured by Titer of ADAs at the Safety Follow-Up Visit | A participant was considered to have developed ADAs if a confirmed positive result was observed at any time during the treatment period post-dose (irrespective of titer value). Samples were collected predose (prior to administering investigational product) and before any hematology/chemistry samples were drawn at that visit. | Safety Follow-Up Visit (32 Weeks) | 
| Immunogenicity of M923 Assessed as the Number of Participants With Neutralizing Anti-drug Antibodies (nADAs) at Baseline | A participant was considered to have developed nADAs if a confirmed positive result was observed at any time during the treatment period post-dose. Samples were collected predose (prior to administering investigational product) and before any hematology/chemistry samples were drawn at that visit. | Baseline (Day 1) | 
| Immunogenicity of M923 Assessed as the Number of Participants With nADAs at Week 4 | A participant was considered to have developed nADAs if a confirmed positive result was observed at any time during the treatment period post-dose. Samples were collected predose (prior to administering investigational product) and before any hematology/chemistry samples were drawn at that visit. | Week 4 | 
| Immunogenicity of M923 Assessed as the Number of Participants With nADAs at Week 12 | A participant was considered to have developed nADAs if a confirmed positive result was observed at any time during the treatment period post-dose. Samples were collected predose (prior to administering investigational product) and before any hematology/chemistry samples were drawn at that visit. | Week 12 | 
| Immunogenicity of M923 Assessed as the Number of Participants With nADAs at Week 24 | A participant was considered to have developed nADAs if a confirmed positive result was observed at any time during the treatment period post-dose. Samples were collected predose (prior to administering investigational product) and before any hematology/chemistry samples were drawn at that visit. | Week 24 | 
| Immunogenicity of M923 Assessed as the Number of Participants With nADAs at the Safety Follow-Up Visit | A participant was considered to have developed nADAs if a confirmed positive result was observed at any time during the treatment period post-dose. Samples were collected predose (prior to administering investigational product) and before any hematology/chemistry samples were drawn at that visit. | Safety Follow-Up Visit (32 Weeks) |