Non-interventional Study on Osilodrostat in Patients With Endogenous Cushing's Syndrome (LINC6)

• ClinicalTrials.gov Identifier: NCT05382156
• Recruitment Status: Recruiting
• First Posted: May 19, 2022
• Last Update Posted: August 22, 2023
• Sponsor: RECORDATI GROUP
• Information provided by (Responsible Party): RECORDATI GROUP

Tracking Information

• First Submitted Date: May 3, 2022
• First Posted Date: May 19, 2022
• Last Update Posted Date: August 22, 2023
• Actual Study Start Date: June 13, 2022
• Estimated Primary Completion Date: June 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 16, 2022)

Incidence of osilodrostat-related adverse events and serious adverse events [ Time Frame: 3 years of treatment with osilodrostat ]

Number of participants with Adverse Events and Serious Adverse Events

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 16, 2022)

• Short and long-term efficacy of osilodrostat [ Time Frame: at baseline before treatment start, after 1 month of treatment, then every 3 months in the first year and every 6 months thereafter through study completion up to three years ]
  Complete response rate: proportion of enrolled patients with mean Urinary Free Cortisol (mUFC) ≤ ULN
• Short and long-term efficacy of osilodrostat [ Time Frame: at baseline before treatment start, after 1 month of treatment, then every 3 months in the first year and every 6 months thereafter through study completion up to three years ]
  Partial response rate: proportion of enrolled patients with ≥ 50% reduction from baseline in mean urinary free cortisol (mUFC), (but mUFC > ULN)
• Short and long-term efficacy of osilodrostat [ Time Frame: at baseline before treatment start, after 1 month of treatment, then every 3 months in the first year and every 6 months thereafter through study completion up to three years ]
  Overall response rate: proportion of enrolled patients with mean urinary free cortisol (mUFC) ≤ ULN or at least 50% reduction from baseline
• Changes in pituitary tumour size [ Time Frame: at baseline before treatment start, after 6 months of treatment, then every 12 months through study completion up to three years ]
  Actual and percentage change from baseline in pituitary tumour size
• Incidence of Adverse Events (Safety and Tolerability) [ Time Frame: 3 years of treatment with osilodrostat ]
  Incidence of adverse events and laboratory abnormalities using the National Cancer Institute-Common Toxicology Criteria (NCI-CTC) grading scale (version 5.0).
• Change of mean urinary free cortisol (mUFC) [ Time Frame: at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years ]
  Actual and percentage change from baseline in mean urinary free cortisol (mUFC)
• Change of Serum Cortisol [ Time Frame: at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years ]
  Actual and percentage change from baseline in Serum Cortisol
• Change of Late Salivary Cortisol [ Time Frame: at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years ]
  Actual and percentage change from baseline in Late Salivary Cortisol
• Change of adrenocorticotropic hormone (ACTH) [ Time Frame: at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years ]
  Actual and percentage change from baseline in adrenocorticotropic hormone (ACTH)
• Normalization of Serum Cortisol [ Time Frame: at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years ]
  Proportion of patients achieving normalisation of Serum Cortisol
• Normalization of Late Salivary Cortisol [ Time Frame: at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years ]
  Proportion of patients achieving normalisation of Late Salivary Cortisol
• Normalization of adrenocorticotropic hormone (ACTH) [ Time Frame: at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years ]
  Proportion of patients achieving normalisation of adrenocorticotropic hormone (ACTH)
• Change in Fasting Glucose [ Time Frame: at baseline before treatment start, then every 3 months through study completion up to three years ]
  Actual and percentage change from baseline in fasting glucose
• Change in HbA1c [ Time Frame: at baseline before treatment start, then every 3 months through study completion up to three years ]
  Actual and percentage change from baseline in HbA1c
• Change in Fasting Lipid Profile [ Time Frame: at baseline before treatment start, then every 3 months through study completion up to three years ]
  Actual and percentage change from baseline in Fasting Lipid Profile
• Change in Serum Insulin [ Time Frame: at baseline before treatment start, then every 3 months through study completion up to three years ]
  Actual and percentage change from baseline in Serum Insulin
• Change in Blood Pressure [ Time Frame: at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years ]
  Actual and percentage change from baseline in Blood Pressure
• Change in Body Weight [ Time Frame: at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years ]
  Actual and percentage change from baseline in Body Weight
• Change in Body Mass Index (BMI) [ Time Frame: at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years ]
  Actual and percentage change from baseline in Body Mass Index (BMI)
• Change in Waist Circumference [ Time Frame: at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years ]
  Actual and percentage change from baseline in Waist Circumference
• Change in Facial Rubor [ Time Frame: at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years ]
  Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Facial Rubor
• Change in Hirsutism [ Time Frame: at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years ]
  Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Hirsutism
• Change in Striae [ Time Frame: at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years ]
  Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Striae
• Change in Supraclavicular fat pad [ Time Frame: at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years ]
  Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Supraclavicular fat pad
• Change in Dorsal fat pad [ Time Frame: at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years ]
  Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Dorsal fat pad
• Change in Proximal muscle wasting (atrophy) [ Time Frame: at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years ]
  Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Proximal muscle wasting (atrophy)
• Change in Central (abdominal) obesity [ Time Frame: at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years ]
  Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Central (abdominal) obesity
• Change in Ecchymoses (bruises) [ Time Frame: at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years ]
  Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Ecchymoses (bruises)
• Changes in Patient-Reported Outcome (PRO) questionnaire Cushing Quality of Life (QoL) [ Time Frame: at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years ]
  Actual and percentage change from baseline in score of PRO questionnaire CushingQoL. The minimum and maximum values are 12 and 60 respectively, where higher score means a better outcome
• Changes in Patient-Reported Outcome (PRO) questionnaire Euro Quality of Life (EQ) - 5 Dimensions (5D) - 5 Levels (5L) [ Time Frame: at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years ]
  Actual and percentage change from baseline in score of PRO questionnaire EQ-5D-5L. The minimum and maximum values for the questions are 11111 and 55555 respectively, where higher score is a worst outcome. For the visual analogue scale minimum and maximum values are 0 and 100 respectively, where higher score means a better outcome
• Changes in Patient-Reported Outcome (PRO) questionnaire Beck Depression Inventory II (BDI-II) [ Time Frame: at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years ]
  Actual and percentage change from baseline in score of PRO questionnaire BDI-II. The minimum and maximum values are 1 and 63 respectively, where higher score means a worse outcome
• Changes in Patient-Reported Outcome (PRO) questionnaire Patient Global Impression of Change (PGIC) [ Time Frame: after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years ]
  Actual and percentage change in score of PRO questionnaire PGIC. The minimum and maximum values of the question are 1 and 7 respectively, where higher score means a better outcome. For the visual analogue scale minimum and maximum values are 0 and 10 respectively, where higher score means a worse outcome

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Non-interventional Study on Osilodrostat in Patients With Endogenous Cushing's Syndrome
• Official Title: A Non-interventional Study to Assess the Long-term Safety and Efficacy of Osilodrostat in Patients With Endogenous Cushing's Syndrome
• Brief Summary: This is a non-interventional, multinational, multi-centre study with primary data collection, to further document the safety and efficacy of osilodrostat administered in routine clinical practice in patients treated with osilodrostat for endogenous Cushing's Syndrome

Detailed Description

This is a non-interventional, multinational, multi-centre study with primary data collection, to further document the safety and efficacy of osilodrostat administered in routine clinical practice in patients treated with osilodrostat for endogenous Cushing's Syndrome. This study is observational in nature and does not impose a therapy protocol, diagnostic/therapeutic interventions or a visit schedule.

Patients with endogenous Cushing's Syndrome who are treated with osilodrostat alone or in combination with other therapies will be considered eligible for study enrolment. Each patient enrolled in the study will be followed up for 3 years from study entry. Patients who discontinue prior to the end of the 3-year period will be followed-up for 3 months after discontinuation of osilodrostat and will be included in the analysis.

The total number of patients enrolled in this study will be at least 100. Assuming a recruitment period of 3 years, the total study duration from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) will be 6 years. The maximum duration for the individual patient is 3 years.

• Study Type: Observational
• Study Design: Observational Model: Other; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Probability Sample
• Study Population: The patient population will consist of adult male and female patients with endogenous Cushing's Syndrome. Eligible patients for the study must be treated with osilodrostat. Investigators need to ensure that patients enrolled in this study meet the study inclusion and exclusion criteria listed in the protocol.
• Condition: Endogenous Cushing's Syndrome

Intervention

Drug: Osilodrostat

oral administration of Osilodrostat tablets at different doses according to patient's need

Other Name: Isturisa

Study Groups/Cohorts

Osilodrostat

Osilodrostat - tablets of 1mg, 5mg, 10mg - based on patients needs - up to 3 years

Intervention: Drug: Osilodrostat

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 16, 2022): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2029
• Estimated Primary Completion Date: June 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Written informed consent obtained prior to registration of any patient data
• Male or female patients aged 18 years or older with endogenous CS treated with osilodrostat. Treatment with osilodrostat can either be initiated at the first visit of the study or can have been initiated before screening.

Exclusion Criteria:

• Patients with exogenous CS
• Patients with Pseudo CS
• Patients participating in an interventional clinical trial with an investigational drug.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Julia Stermenska; +41 79 440 58 97 ext 00; stermenska.j@recordati.com

Contact: Massimo Casi, MD; +30 0248787 ext 456; casi.m@recordati.it

• Listed Location Countries: France, Germany, United States

Administrative Information

• NCT Number: NCT05382156
• Other Study ID Numbers: LCI699-RECAG-PASS-0572
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: RECORDATI GROUP
• Original Responsible Party: Same as current
• Current Study Sponsor: RECORDATI GROUP
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Mario Maldonado, MD; Recordati AG - Head of Clinical Development

• PRS Account: RECORDATI GROUP
• Verification Date: August 2023