A phase III, Multicentre, Open-Label, Chronic dosing, Extension Study to Evaluate the Long-term Safety of Tozorakimab in Participants with Chronic Obstructive Pulmonary Disease (COPD) With a History of COPD Exacerbations (ROMEO)

The primary objective of this phase III extension study is to describe the long-term safety and tolerability of tozorakimab as an add-on therapy to standard of care in participants with chronic obstructive pulmonary disease (COPD) who have a documented history of COPD exacerbations. This objective addresses the critical need to establish the safety profile of tozorakimab during prolonged administration in a patient population characterized by recurrent exacerbations, which contribute significantly to disease progression and healthcare burden. The study employs a multicentre, open-label, chronic dosing design to assess adverse events and tolerability over an extended treatment period of up to 36 months with subcutaneous administration of tozorakimab solution for injection.

The sponsor did not provide information regarding the total number of participants for this clinical trial. The study enrolled **adult and elderly participants** of **both genders** diagnosed with **Chronic Obstructive Pulmonary Disease (COPD)**. The trial population was specifically selected from individuals who had previously participated in the predecessor studies TITANIA, MIRANDA, or PROSPERO. Eligible participants included those who had completed the treatment period and follow-up without premature discontinuation from the investigational medicinal product in TITANIA or MIRANDA, as well as those from PROSPERO who had either completed follow-up or continued receiving treatment up to the primary reporting phase and attended the end-of-study visit 12 weeks after the last dose. All participants were required to be affiliated with the French Social Security system, willing to continue using agreed-upon contraceptive methods from their predecessor studies, and capable of providing signed informed consent. The study population included a **vulnerable population**.

This is a **phase III**, **multicentre**, **open-label**, chronic dosing extension study designed to evaluate the long-term safety and tolerability of **tozorakimab** administered as an add-on to standard of care in participants with **chronic obstructive pulmonary disease** with a history of **COPD exacerbations**. The study represents an extension protocol for participants who have previously been enrolled in predecessor studies (TITANIA, MIRANDA, or PROSPERO) and have completed the treatment period and follow-up without premature discontinuation from the investigational medicinal product.

The **investigational medicinal product** tozorakimab is a **solution for injection** containing tozorakimab as the active substance, administered via the **subcutaneous** route. The maximum daily dose is **20 mg**, with a maximum total dose of **21,600 mg** over a treatment period of up to **36 months**. The study is scheduled to commence recruitment in November 2025, with an estimated completion date in December 2028.

The **primary endpoint** focuses on comprehensive safety assessments, including the occurrence and frequency of **adverse events**, their relationship to the investigational medicinal product as assessed by the investigator, intensity, seriousness, deaths, adverse events leading to discontinuation of the investigational medicinal product, and other significant adverse events. Laboratory assessments will also be conducted as part of the safety evaluation.

Eligible participants must have been previously randomized in one of the predecessor studies and completed the treatment period and follow-up without premature discontinuation from the investigational medicinal product. For participants from the PROSPERO study, those who continued to receive the investigational medicinal product up to the primary reporting and attended the end of study visit 12 weeks after the last dose are also eligible. Participants must be capable of providing **signed informed consent** and willing to continue using contraceptive methods as agreed to in the predecessor studies. French participants must be affiliated with the French Social Security system.

The expected duration of participant involvement extends up to 36 months of treatment. Conditions that may lead to early termination from the study include the occurrence of adverse events necessitating discontinuation of the investigational medicinal product, withdrawal of consent, or other safety concerns as determined by the investigator or sponsor.

**Tozorakimab** is administered as a **solution for injection** via the **subcutaneous route**. The **active substance** is tozorakimab, which is classified as a protein of other origin. The maximum daily dose is **20 mg**, with a maximum total dose of **21,600 mg** administered over a maximum treatment period of **36 months**. Tozorakimab is used as an add-on therapy to **standard of care** in participants with **chronic obstructive pulmonary disease** who have a history of COPD exacerbations. The investigational medicinal product is manufactured by AstraZeneca AB and is designated as the test product in this phase III, multicentre, open-label, chronic dosing extension study.

The primary efficacy assessment in this clinical trial focuses on evaluating the long-term safety and tolerability of tozorakimab when administered as an add-on to standard of care in participants with chronic obstructive pulmonary disease (COPD) with a history of COPD exacerbations. The primary endpoints include the evaluation of adverse events and laboratory assessments. Adverse event assessments will capture the occurrence and frequency of events, the relationship to the investigational medicinal product as determined by the investigator, the intensity of events, seriousness, deaths, adverse events leading to discontinuation of the investigational medicinal product, and other significant adverse events. The maximum treatment period for participants in this extension study is 36 months.