Cushing's Disease
Conditions
Brief summary
This trial will evaluate the effects of Lu AG13909 in adult participants with Cushing's disease (CD). CD is a rare and serious disorder where the body makes too much of a hormone called cortisol. The main goals of this trial are to learn about 1. the effect of Lu AG13909 on cortisol levels. 2. the safety and tolerability of Lu AG13909. 3. the pharmacokinetic parameters of Lu AG13909 (how the drug is absorbed, distributed, and processed by the body).
Detailed description
This trial is divided into 3 parts: * Part A, consisting of 3 periods: an intravenous (IV) Titration Period, a subcutaneous (SC) Period, and a Safety Follow up Period * Part B, consisting of 3 periods: a SC Titration Period, a Maintenance Period, and a Safety Follow-up Period * Extension Period, consisting of a Long-Term Efficacy/Safety Period after Part B and a Safety Follow-up Period
Interventions
DRUGLu AG13909
Solution for injection/infusion
Sponsors
H. Lundbeck A/S
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* The participant is a man or woman with a confirmed diagnosis of adrenocorticotropic hormone (ACTH) driven CD of pituitary source as per current guidelines * Morning plasma ACTH levels \> lower limit of normal (LLN) and * Evidence of a pituitary origin of the excess ACTH: i. Either MRI confirmation of pituitary adenoma \>6 millimeters (mm), or ii. inferior petrosal sinus gradient \>2, or iii. histopathology confirmation of ACTH-secreting tumour * The participant has a 24-hour UFC \>1.5 × ULN (the mean of ≥3 days of 24-hour urine collection). * Apart from CD and associated well-controlled comorbidities (for example, diabetes mellitus and hypertension), the participant is generally healthy in the opinion of the investigator and based on medical history, physical examination, vital signs, electrocardiogram (ECG), and the results of the safety laboratory tests. * For participants on medical treatment for hypercortisolism due to CD, pre-defined washout periods must be completed prior to the Baseline efficacy assessments.
Exclusion criteria
* The participant is pregnant, breastfeeding, intends to become pregnant, or is of child-bearing potential and not willing to use adequate contraceptive methods. * The participant has a clinically significant abnormal laboratory value, ECG parameter, vital signs value, or other safety findings at the Screening Visit that indicate a potential risk to the participant's safety if enrolled, in the opinion of the investigator. * The participant has a history of known hypersensitivity or intolerance to Lu AG13909 or its excipients. * The participant has immediate need for pituitary surgery within 6 months from screening in the opinion of the investigator. * The participant has severe CD per investigator judgement; among others, this could be participants with: i. poorly controlled hypertension ii. poorly controlled diabetes mellitus iii. severe psychiatric illness iv. compression of the optic chiasm causing any visual field defect or risk thereof v. very high risk of thromboembolic events * The participant had pituitary surgery \<3 month prior to screening. * The participant had pituitary radiotherapy within the last 10 years. Other protocol-defined criteria apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A & Part B: Urinary Free Cortisol (UFC) Complete Response: mean UFC (mUFC) ≤ Upper Limit of Normal (ULN) at the end of the IV/SC Titration Period | Up to 490 days |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Up to 1023 days |
| AUC0-tau,ss: Area Under the Plasma Concentration Curve of Lu AG13909 at Steady State | Up to 1037 days |
| CL: Systemic Clearance of Lu AG13909 | Up to 1037 days |
| t½: Elimination Half-life of Lu AG13909 | Up to 1037 days |
| Vd: Apparent Volume of Distribution of Lu AG13909 | Up to 1037 days |
| SC Bioavailability (F) of Lu AG13909 | Up to 1037 days |
| Number of Participants With Anti-Drug Antibodies (ADAs) | Up to 1037 days |
| Part A Only: Cmax: Maximum Observed Plasma Concentration of Lu AG13909 | Up to 323 days |
| Part A Only: Tmax: Nominal Time Corresponding to the Occurrence of Cmax of Lu AG13909 | Up to 323 days |
| Part A & Part B: Ctrough: Minimum Observed Concentration of Lu AG13909 | Up to 659 days |
| Part A & Part B: Ttrough: Nominal Time Corresponding to the Occurrence of Ctrough | Up to 659 days |
| UFC Complete Response (mUFC ≤ ULN) or Partial Response (≥50% Reduction in UFC from Baseline and mUFC >ULN) at the End of the IV/SC Titration Period | Up to 491 days |
| Maintenance of UFC Complete Response (mUFC ≤ULN) at the End of the Part B Maintenance Period | Up to 337 days |
| Part A and Part B: Percentage Change from Baseline in mUFC at the End of the Titration Period and the Completion Visit | Baseline, up to 561 days |
| Part A and Part B: UFC Complete Response (mUFC ≤ ULN) or Partial Response (≥50% Reduction in UFC from Baseline and mUFC >ULN) at the Completion Visit | Up to 561 days |
| Part A and Part B: Late Night Salivary Cortisol (LNSC) Complete Response (Mean LNSC (mLNSC)≤ULN) or Partial Response (≥50% Reduction from Baseline in LNSC and mLNSC >ULN) at the End of the Titration Period and the Completion Visit | Up to 561 days |
Countries
France, Georgia, Hungary, Italy, Poland, Romania, Spain, United Kingdom, United States
Contacts
CONTACTEmail contact via H. Lundbeck A/S
STUDY_DIRECTOREmail contact via H. Lundbeck A/S
HQ_Medinfo@Lundbeck.com
Outcome results
None listed