Full protocol title prospective observational study: “Comparative study of the use of Multigam IV (5% vs. 10%) as substitution therapy in patients with a secondary immunodeficiency due to a hematological disorder to evaluate infusion time, tolerability and satisfaction. A monocentric observational Belgian study.” Protocol acronym/short title: MULTISIM/Comparison of Multigam IV 5% and Multigam IV 10% in immunocompromised patients. Version and date of final protocol: Version 3 - 8 September 2017 Sponsor: Name: UZLeuven Address: Herestraat 49, 3000 Leuven Principal investigator: Name: Professor Dr Delforge Michel Address: Herestraat 49, 3000 Leuven Email: [email protected] Page 1 of 19 Signature _________________________ ____________________ Principal Investigator Date Page 2 of 19 Table of contents 1. Study synopsis ................................................................................................................................. 5 2. Background and rationale ............................................................................................................... 8 3. Study objectives and design ............................................................................................................ 9 3.1 Study objectives ........................................................................................................................ 9 3.2 Primary endpoints ..................................................................................................................... 9 3.3 Secondary endpoints ................................................................................................................. 9 3.4 Study design .............................................................................................................................. 9 3.5 Study diagram ............................................................................................................................ 9 3.6 Study flowchart ....................................................................................................................... 10 4. Selection and exclusion of participants ......................................................................................... 10 4.1 Inclusion criteria ...................................................................................................................... 10 4.2 Exclusion criteria ..................................................................................................................... 10 4.3 Expected duration of study ..................................................................................................... 10 5. Study actions per visit ................................................................................................................... 11 5.1 Study visit 1 ............................................................................................................................. 11 5.2 Study visit 2 ............................................................................................................................. 11 6. Data collection ............................................................................................................................... 11 7. Assessment of efficiency ............................................................................................................... 12 8. Assessment of safety ..................................................................................................................... 12 8.1 Specification, timing and registration of safety parameters ................................................... 12 8.2 Procedures for registration and reporting of adverse events (AE) ......................................... 12 9. Statistics ........................................................................................................................................ 15 9.1 Sample size .............................................................................................................................. 15 9.2 Analysis .................................................................................................................................... 15 10. Direct access to source data and documents ............................................................................ 15 11. Ethical and regulatory compliance ............................................................................................ 15 12. Data handling and management ............................................................................................... 16 13. Publication policy ...................................................................................................................... 16 14. Insurance/compensation .......................................................................................................... 17 Page 3 of 19 15. Financial aspects ........................................................................................................................ 17 16. References ................................................................................................................................. 17 17. Annex ......................................................................................................................................... 18 Page 4 of 19 1. Study synopsis Comparative study of the use of Multigam IV (5% vs. 10%) Clinical trial title as substitution therapy in patients with a secondary immunodeficiency due to a hematological disorder to evaluate infusion time, tolerability and satisfaction. A monocentric observational Belgian study. Protocol short title/Acronym MULTISIM/Comparison of Multigam IV 5% and Multigam IV 10% in immunocompromised patients. Sponsor name UZ Leuven Principal investigator Professor dr. Delforge Michel Secondary immune deficiencies in patients with an Medical condition or ilness underlying hematological disorder. Purpose of the clinical trial Evaluation of infusion time, safety and tolerance of Multigam 10% compared to Multigam 5%. Primary objective Assess the administration of Multigam 10% compared to Multigam 5% to shorten the infusion time without additional side effects and loss of quality of care. Evaluate the tolerability and infusion related side Secondary objectives effects. Evaluate patient satisfaction. Evaluate the number of care actions required. Evaluate nursing staff satisfaction. In this non-interventional, monocentric, observational study, the administration of Multigam 10% will be Setup compared with the standard (Multigam 5%) in patients with a secondary immunodeficiency due to a hematological disorder. Patients who are being treated with Multigam because of Page 5 of 19 their secondary immunodeficiency will be evaluated for inclusion. The last administration of Multigam 5% will serve as a control. During this check, different parameters will be evaluated: -Infusion time (hours) -Hospitalization time at the oncological day clinic (hours) -Side effects (via CTCAE v4.03) -Nursing staff care actions Subsequently, an identical evaluation will take place at the first administration of Multigam 10% and the satisfaction of the patient and the nursing staff will also be assessed. The results will be analyzed and compared. Patients can then receive Multigam 10% or Multigam 5% according to their preference. Screening Multigam 5% administration First evaluation Multigam 10% administration Final evaluation Primary: Endpoints To compare the infusion time (hours) and tolerance of Multigam 10% and the standard administration of Multigam 5%. Page 6 of 19 Secondary: Assess the tolerance and patient satisfaction of Multigam 5% vs. Multigam 10% via: - Patient questionnaire - Scoring of side effects via CTCAE v4.03 Assess nursing staff care actions Assess the satisfaction of the nursing staff (questionnaire) Patient characterization (age, gender, disorder) 30 patients with a secondary immunodeficiency due to a Population hematological disorder. Age ≥ 18 years Secondary immunodeficiency due to a hematological Inclusion criteria disorder Patient received at least 2x Multigam 5% No side effects (grade 2 or higher according to CTCAE v4.03) during their last 2 Multigam 5% infusions Patient needs at least 2x Multigam Signed informed consent form Patient received less than 2x Multigam 5% Exclusion criteria Side effects (grade 2 or higher according to CTCAE v4.03) during their last 2 Multigam 5% infusions Patient refuses to participate in the study Maximum duration of study/treatment 2 months Version and date of final protocol Version 3 – 8 September 2017 Page 7 of 19 2. Background and rationale Background The immune system ensures the detection and elimination of pathogens and even transformed cells. However, normal functioning can be disrupted by a variety of factors. Both primary and secondary causes can lead to an immune deficiency with increased vulnerability for infections (Cooper, et al. 2003, Shinen & Shearer, 2008). Secondary immune deficiencies can be caused by various diseases (lymphoproliferative disorders, infections, ...) and therapies (immunosuppressants, anti-inflammatory drugs, ...). In lymphoproliferative disorders such as chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), both treatment and the disease itself contribute to a secondary immunodeficiency. In order to strengthen the resistance in these patients, substitution therapy with immunoglobulins can be started in cases of recurrent infections (Friman, et al. 2016). Intravenous