abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. The synopsis which is part of the clinical study report had been prepared in accordance with best practice and applicable legal and regulatory requirements at the time of study completion. The synopsis may include approved and non approved uses, doses, formulations, treatment regimens and/or age groups; it has not necessarily been submitted to regulatory authorities. A synopsis is not intended to provide a comprehensive analysis of all data currently available regarding a particular drug. More current information regarding a drug is available in the approved labeling information which may vary from country to country.. Additional information on this study and the drug concerned may be provided upon request based on Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. The synopsis is supplied for informational purposes only in the interests of scientific disclosure. It must not be used for any commercial purposes and must not be distributed, published, modified, reused, posted in any way, or used for any other purpose without the express written permission of Boehringer Ingelheim.
Page 1 of 5 1 SYNOPSIS Title of Trial: Assessment of Real-life Patient Handling Experience of Administered Subcutaneously with an Autoinjector in Patients with Rheumatoid Arthritis: an Open-label, Interventional Clinical Trial Followed by an Extension Phase of Administered with a Prefilled Syringe Coordinating Investigator: Dr. Trial Sites: 19 trial sites in Poland and the United States Publication (Reference): None Objectives: The primary objective of the Autoinjector Assessment Period was to assess the real-life patient handling experience of patients with rheumatoid arthritis (RA) who self-injected subcutaneously using an autoinjector. The objectives of the Extension Phase were to provide patients with additional exposure to and to enhance the safety database for this compound. Methodology: is a proposed biosimilar to Humira (adalimumab). Humira has received regulatory approval for RA in the United States, the European Union, and many other countries. Patients with RA eligible and willing to participate in this trial self-injected 4 subcutaneous (SC) injections of (1 injection every other week) with an autoinjector (Autoinjector Assessment Period). After adequate training by qualified trial site personnel, the first injection was administered by the patient, under the supervision and guidance of the qualified trial site personnel. This supervised training injection did not contribute to the evaluation of the primary and secondary endpoints. The 3 subsequent injections were done at the trial site under the supervision of qualified trial site personnel. Observations of autoinjector handling events during the injection were recorded independently by both trial site personnel and the patient using standardized questionnaires. Patients continued their nonbiologics treatments for their condition as determined by the Investigator, including their usual prescribed concomitant therapies. A patient s eligibility was not influenced by their methotrexate (MTX) or any other disease-modifying antirheumatic drug (DMARD) therapy. Patients
Page 2 of 5 were permitted to receive MTX or any other DMARD therapy as part of their standard of care during the trial. Based on the Investigator assessment of patient eligibility, qualified patients who completed the Autoinjector Assessment Period per the clinical trial protocol were offered the opportunity to receive an additional 42 weeks of treatment (Extension Phase) with administered using pre-filled syringes (PFSs). During the Extension Phase, patients self-injected up to 22 injections of (1 injection every other week) using PFSs. During the trial, patients received up to 26 injections of (4 by autoinjector; 22 by PFS). Number of Subjects (Planned and Analyzed): A total of 70 subjects were planned; 103 subjects consented to participate; and 77 subjects were enrolled. A total of 77 subjects were analyzed for safety. No efficacy parameters were evaluated during this trial. Diagnosis and Main Criteria for Inclusion: Eligible patients were male and female adults between 18 and 80 years of age (inclusive) who had been diagnosed with moderately to severely active RA that was not adequately controlled by DMARDs. Prior treatment with biologics was permitted, but patients with previous experience of self-administering medications using an autoinjector or pen were excluded from the trial. Test Product, Dose and Mode of Administration, Batch Numbers: solution for injection, 40 mg/0.8 ml, administered by SC injection every 2 weeks by autoinjector or PFS. Batch numbers for autoinjectors: B151002779, B151002691, and B161000181. Batch numbers for PFSs: B151002877 and B161000284. Duration of Treatment: 7-week Autoinjector Assessment Period; 42-week optional Extension Phase Criteria for Evaluation: Efficacy: No efficacy parameters were evaluated during this trial. Safety Endpoints: Primary: The primary endpoint for the Autoinjector Assessment Period was the percentage of successful self-injections as reported in the questionnaires completed by both the trial site personnel and the patient during the Autoinjector Assessment Period, analyzing all self-injections occurring after the training self-injection up to the End-of-treatment (EoT) Visit. During this period of the trial, patients performed a total of 3 SC injections of trial drug in their abdomen or thigh region using an autoinjector and at the trial site under supervision by the Investigator or the qualified trial site personnel.
Page 3 of 5 Secondary: The secondary endpoints for the Autoinjector Assessment Period were assessed in the safety analysis set at the EoT Visit on Day 50 (or 1 week after the last self-injection of by autoinjector). The secondary endpoints were the following: The frequency of any autoinjector handling event during the self-injection process as reported in the questionnaires (Questions 3a, 3b, and 3c) completed by both the qualified trial site personnel and the patient during the Autoinjector Assessment Period. An autoinjector handling event was any of the following events preventing the patient from successfully self-injecting the full contents of the autoinjector and occurring after the training self-injection up to the EoT Visit: - Removing the cap of the autoinjector (3a) - Pressing the injection button of the autoinjector (3b) - Holding the autoinjector down against the skin until the injection is completed (3c) The proportion of patients with local injection-site reactions The proportion of patients with drug-related AEs per Investigator assessment Further: The further endpoint was the autoinjector robustness, as defined by the number of returned autoinjectors with any signs of damage, malfunctioning, or injection incompleteness identified through visual inspection by the Sponsor device engineers. Also, autoinjectors that did not function normally (ie, Question 3a or 3b had been ticked) and the corresponding complaint forms were to be returned to the Sponsor. These autoinjectors underwent a thorough technical inspection by device engineers to identify the root cause of the complaint. Safety Assessments: For the Week 7 primary analysis, safety was collected and assessed up to Day 50 (EoT Visit) for the Autoinjector Assessment Period and up to Week 60 (ie, 10 weeks after the End-of-Study [EoS] Visit) for the Extension Phase. During the Autoinjector Assessment Period for the Week 7 primary analysis, safety was assessed through physical examination, height (at screening only), weight, concomitant therapies, vital sign measurements, laboratory tests (serum chemistry, hematology), QuantiFERON -TB Gold test, urinalysis, electrocardiogram (ECG), adverse event (AE) monitoring, and questionnaire administration. Safety data were collected through the electronic case report form (ecrf). During the Extension Phase with PFS, safety was assessed through physical examination, weight, concomitant therapies, vital sign measurements, laboratory tests (serum chemistry, hematology), QuantiFERON-TB Gold test, urinalysis, ECG, patient diaries, and AE monitoring. Safety data were collected through the ecrf and source data.
Page 4 of 5 Statistical Methods: Analyses were based on descriptive statistics for the outcome of all questionnaires, local injection-site reactions, and safety assessments. The 95% Wilson score confidence interval was displayed for the primary endpoint, the percentage of successful injections. Summary and Conclusions of the Week 7 Primary Analysis Patient Disposition and Demographics: A total of 103 patients were screened at 19 trial sites, 77 patients were assigned to treatment, 77 patients were treated, and 73 patients (94.8%) completed the Autoinjector Assessment Period. Thirty patients (39.0%) were treated at 10 sites in Poland, and 47 patients (61.0%) were treated at 9 sites in the United States. As of the data cut-off for this primary analysis, 72 patients (93.5%) had entered and 2 patients (2.6%) had discontinued the Extension Phase. Fifty-two patients received at least 1 dose of trial drug by PFS. No patient had completed the Extension Phase (Day 351), as the Extension Phase is ongoing at the time of this report. Safety Results: Two hundred sixteen (99.1%) out of 218 initial self-injections of with the autoinjector, performed by 77 patients on Days 15, 29, and 43 of the Autoinjector Assessment Period, were reported by trial site personnel and the patients to be successful. In both cases of unsuccessful initial attempts, the patients and trial site personnel indicated on their questionnaires that the autoinjector button could not be pressed (ie, Question 3b had been ticked). Both patients were able to perform a successful selfinjection with a second autoinjector immediately after the first attempt. The 2 autoinjectors involved in the initial unsuccessful self-injections, along with 2 autoinjectors involved in unsuccessful initial attempts during training on Day 1, were returned to the Sponsor for technical inspection. Because all test parameters were within specification for the autoinjectors, no technical complaints were confirmed. The unsuccessful attempts were therefore attributed to potential use error, of which the residual risk has been assessed acceptable. The first 109 autoinjectors that functioned normally and were returned to the Sponsor for robustness testing were found to be robust after real-life usage and as per the current test protocol. All autoinjectors passed visual and manual inspection and showed no signs of damage, malfunction, or injection incompleteness. During the Autoinjector Assessment Period, 31 patients (40.3%) were reported with at least 1 TEAE, and 9 patients (11.9%) were reported with at least 1 TEAE considered by the Investigator to be related
Page 5 of 5 to the trial drug. Two patients (2.6%) were reported with 4 TEAEs of severe intensity: oesophageal carcinoma, anaemia, drug hypersensitivity, and depression. No deaths were reported up to the cut-off date for the Week 7 primary analysis. Four SAEs were reported by 2 patients during the Autoinjector Assessment Period, none of which were considered by the Investigator to be treatment-related. An additional SAE was reported by a patient during the Extension Phase, which also was considered not related to treatment. Two patients (2.6%) were reported with TEAEs that led to trial drug discontinuation. There were no reports of serious infection, DILI, and anaphylactic reaction (all CTP-defined AESIs). The proportion of patients with drug-related AEs per Investigator assessment during the Autoinjector Assessment Period was 11.9%. Injection-site reactions were reported by 5 patients (6.5%) during the Autoinjector Assessment Period. The majority of the reactions directly reported by patients occurred after the injection on Day 1. None of the injection-site reactions were reported as SAEs. One patient discontinued trial drug before receiving a second injection because of an injection-site reaction and rash reported on Day 12. There were no clinically meaningful changes from Baseline to data cut-off for chemistry, hematology, and urinalysis laboratory values. One patient had a negative TB test at Baseline and a positive test at Day 50. Conclusions: This report presents complete data from the Autoinjector Period of the trial. In this period, patients with moderate to severe RA without prior experience of self-injections with autoinjector or pen were able to self-administer SC using an autoinjector at a very high success rate (99.1%). Device engineers evaluated the robustness of 109 autoinjectors that performed normally and were returned to the Sponsor, and also conducted technical inspections of 4 autoinjectors involved in unsuccessful self-injections. The inspections revealed no mechanical or structural failures in any of the devices. Administration of with an autoinjector was generally well tolerated. There was a low frequency of injection-site reactions during the trial, with the majority of reactions directly reported by patients occurring after the initial injection.