Long-term Safety Evaluation of Octreotide Hydrochloride Subcutaneous Depot (CAM2029) in Patients with Acromegaly: A Phase 3, Open-label, Single-arm, Multicenter Study

The primary objective of this clinical trial is to assess the overall **safety** and tolerability of CAM2029, an octreotide subcutaneous depot, in patients with **acromegaly**. This is clinically relevant as ensuring the safety and tolerability of long-term treatments is crucial for managing chronic conditions like acromegaly, which can have significant impacts on patient health and quality of life.

Secondary objectives include: - Assessing the efficacy of CAM2029 based on biochemical characteristics. - Evaluating self- and partner administration. - Measuring plasma concentration of octreotide post-administration. - Assessing patient satisfaction with CAM2029. - Measuring the effects of CAM2029 on quality of life (QoL). - Evaluating health economic outcomes and solicited safety assessments post-treatment.

The clinical trial involves a total of **51 participants** diagnosed with **acromegaly**, a condition characterized by excessive growth hormone production. The study population includes both male and female subjects aged 18 years and older. Participants were selected based on their ability to provide informed consent and a confirmed diagnosis of acromegaly, with a history of treatment using a stable dose of octreotide LAR or lanreotide ATG for at least three months prior to screening. The trial population is characterized by adequate liver, pancreatic, renal, and bone marrow functions, as well as a normal ECG. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, indicating that special considerations are in place to ensure the safety and ethical treatment of participants.

The clinical trial is a **Phase 3**, open-label, single-arm, multi-center study designed to assess the long-term safety of **octreotide subcutaneous depot** (CAM2029) in patients diagnosed with **acromegaly**. The trial aims to evaluate the overall safety and tolerability of CAM2029, with a primary focus on characterizing adverse events. Secondary endpoints include the assessment of **insulin-like growth factor 1 (IGF-1)** and **growth hormone (GH)** levels, patient satisfaction, and quality of life metrics over time. The trial is expected to conclude by May 31, 2025, with recruitment having commenced on October 10, 2019.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and previous treatment stability. The main part of the trial requires participants to have been on a stable dose of octreotide LAR or lanreotide ATG for at least three months prior to screening. Follow-up visits will occur regularly to monitor safety, efficacy, and patient-reported outcomes. The end-of-study visit will mark the completion of the trial, with the possibility of continuation into an extension part for those meeting specific criteria.

The expected duration of participant involvement is up to 104 weeks, with conditions for early termination including withdrawal of consent, adverse events, or non-compliance with the study protocol. Participants who complete the main part of the trial and attend the Week 52 visit may be eligible to continue into the extension part, provided they give informed consent and meet the continuation criteria. The trial's design ensures rigorous monitoring and data collection to support the evaluation of CAM2029's long-term safety profile in the target population.

The clinical trial involves the administration of **CAM2029**, a formulation of **octreotide hydrochloride** designed as a subcutaneous depot. This experimental medication is provided in the form of a **solution for injection**. The primary active substance, **octreotide hydrochloride**, is a synthetic octapeptide that mimics natural somatostatin, a hormone that inhibits the secretion of several other hormones. The pharmaceutical form is a solution for injection, intended for **subcutaneous use**. The dosing regimen for CAM2029 is structured to deliver a maximum daily dose of 20 mg, with a total maximum dose of 520 mg over a treatment period of up to 104 weeks. The administration frequency is determined by the study protocol, ensuring consistent delivery of the medication to maintain therapeutic levels.

In addition to the primary experimental treatment, a second formulation of CAM2029 is also utilized within the trial. This formulation is identical in its pharmaceutical form and route of administration, being a solution for injection intended for subcutaneous use. However, the dosing differs, with a maximum daily dose of 10 mg and a total maximum dose of 260 mg over the same treatment period of 104 weeks. Both formulations are developed by CAMURUS AB and are classified as orphan drugs, indicating their use in treating rare conditions such as **acromegaly**. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol and to assess the long-term safety and tolerability of CAM2029 in patients with acromegaly.

The efficacy of the clinical trial involving CAM2029 (octreotide subcutaneous depot) for the treatment of **acromegaly** will be assessed through a series of primary and secondary endpoints. The primary endpoint focuses on the characterization of adverse events (AEs) throughout both the main and extension parts of the trial. Secondary endpoints include the proportion of patients achieving specific levels of insulin-like growth factor 1 (IGF-1) and growth hormone (GH) at designated time points, such as Week 50 and Week 52. Specifically, the trial will evaluate the proportion of patients with mean IGF-1 levels ≤1 x upper limit of normal (ULN) and <1.3xULN, as well as mean GH levels <2.5 µg/L and <5.0 µg/L at Week 52.

Additional secondary endpoints involve the assessment of octreotide plasma concentrations over time, patient and partner competence in administering CAM2029, and treatment satisfaction using the Treatment Satisfaction Questionnaire for Medication (TSQM) scores across all four domains: effectiveness, side effects, convenience, and satisfaction. Patient satisfaction will also be measured at Week 24 and Week 52. Changes from baseline in the Acromegaly Quality of Life Questionnaire (AcroQoL) and EuroQoL 5-dimension 5-level (EQ-5D-5L) scores will be evaluated. In the extension part of the trial, IGF-1 and GH levels will be monitored over time, along with TSQM, AcroQoL, EQ-5D-5L, and Short Form-36 (SF-36) scores. Work Productivity and Activity Impairment (WPAI) scores, laboratory values, vital signs, ECG readings, and gallbladder imaging will also be assessed over time.