Phase 2 Multicenter Double-Blind Study of Subcutaneous PF-06480605 in Moderate to Severe Active Crohn's Disease

The primary objective of this phase 2, multicenter, double-blind, two-arm study is to evaluate the **safety** and **tolerability** of RO7790121 in subjects with moderate to severe active **Crohn's disease**. This is clinically relevant as it aims to ensure that the investigational drug can be administered safely to patients, which is a critical step before considering its efficacy and potential approval for therapeutic use.

Secondary objectives include:

• Determining the efficacy of RO7790121 in the induction of endoscopic response by SES-CD at week 14.
• Assessing the efficacy of RO7790121 in the induction of clinical remission by CDAI at week 14.
• Evaluating the efficacy of RO7790121 in the induction of clinical remission by PRO2 at week 14.
• Understanding the pharmacokinetics (PK) of RO7790121 in moderately to severely active Crohn's disease.

The clinical trial involves a total of **7 participants** diagnosed with **Crohn's disease**. The study population includes individuals of any gender, aged between **18 and 75 years**. Participants were selected based on their confirmed diagnosis of ileal, ileocolonic, or colonic Crohn's disease for at least 12 weeks prior to the baseline visit, with appropriate documentation of biopsy-proven disease. The trial does not include a vulnerable population. Participants' general health status is characterized by a Crohn's Disease Activity Index (CDAI) score ranging from 220 to 450, determined at screening. Lifestyle considerations such as diet, physical activity, or habits are not specified. The selection criteria required written informed consent according to local guidelines, signed and dated by the participant before any study-specific procedures, sampling, or analysis were conducted.

The clinical trial is a **Phase II**, multi-center, double-blind, two-arm study designed to evaluate the safety and tolerability of the investigational product RO7790121 in subjects with moderate to severe active **Crohn's disease**. The trial employs a randomized, controlled methodology to ensure the reliability and validity of the results. The study is expected to run until December 31, 2029, with recruitment having commenced on September 11, 2023. Participants will be involved in the study for a maximum treatment period of 56 days, during which they will receive the investigational product, RVT-3101, administered as a solution for injection.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as age, confirmed diagnosis of Crohn's disease, and a Crohn's Disease Activity Index (CDAI) score between 220-450. Following the screening, participants will undergo a baseline visit (W1, D1) to establish initial health parameters. Subsequent follow-up visits will occur at regular intervals to monitor the incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and any adverse events leading to discontinuation. The primary endpoint focuses on the safety profile of the investigational product, while secondary endpoints include the proportion of participants achieving endoscopic response and clinical remission at week 14.

The end-of-study visit will conclude the participant's involvement, assessing the overall health status and any long-term effects of the treatment. Participants may be subject to early termination from the study if they experience significant adverse events or fail to adhere to the study protocol. The trial is not classified as low intervention, given its phase and the investigational nature of the product. The study aims to provide valuable insights into the treatment of Crohn's disease, contributing to the development of effective therapeutic strategies.

The clinical trial involves the administration of **RVT-3101**, an investigational medicinal product formulated as a **solution for injection**. The active substance in RVT-3101 is **PF-06480605**, classified as a protein of other origin, specifically an **IgG1 monoclonal antibody**. The pharmaceutical form is designed for subcutaneous administration. The dosing regimen for RVT-3101 is determined by the study protocol, with a maximum treatment period of 56 days. The specific dosage and frequency of administration are not detailed in the provided data. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol.

In this study, RVT-3101 is the primary experimental treatment. There is no mention of a placebo or comparator treatment being used alongside RVT-3101 in the provided data. The trial aims to evaluate the safety and tolerability of the investigational product in subjects with moderate to severe active **Crohn's disease**. The study is conducted under a double-blind, two-arm design, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby minimizing bias.

The efficacy of the investigational product, RO7790121, in the treatment of moderate to severe active **Crohn's Disease** will be assessed through several predefined endpoints. The primary efficacy endpoint is the participant incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events (AEs) leading to discontinuation throughout the study. Secondary efficacy endpoints include the proportion of participants achieving an endoscopic response, defined as a decrease in the Simple Endoscopic Score for Crohn's Disease (SES-CD) by at least 50% from baseline at week 14, as assessed by central read. Additionally, the proportion of participants achieving clinical remission, indicated by a Crohn's Disease Activity Index (CDAI) score of less than 150 at week 14, will be evaluated. Clinical remission will also be assessed using patient-reported outcomes (PRO2), defined as an average daily very soft or liquid stool frequency of 2.8 or less and an abdominal pain score of 1 or less, with scores not worse than baseline, at week 14. Pharmacokinetic parameters of RO7790121, such as trough concentration (Ctrough), will also be measured.