AG13909 for Cushing's disease

Inclusion criteria

• {"criterion_text":"- The participant is a man or woman with a confirmed diagnosis of adrenocorticotropic hormone (ACTH) driven CD of pituitary source as per current guidelines\n- Morning plasma ACTH levels > lower limit of normal (LLN)\n- 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\n- The participant has a 24-hour UFC >1.5 × ULN (the mean of ≥3 days of 24-hour urine collection).\n- 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.\n- 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

• {"criterion_text":"- The participant is pregnant, breastfeeding, intends to become pregnant, or is of child-bearing potential and not willing to use adequate contraceptive methods.\n- 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.\n- The participant has a history of known hypersensitivity or intolerance to Lu AG13909 or its excipients.\n- The participant has immediate need for pituitary surgery within 6 months from screening in the opinion of the investigator.\n- 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\n- The participant had pituitary surgery <6 weeks prior to screening.\n- The participant had pituitary radiotherapy within the last 3 years."}

Primary endpoints

• {"endpoint_text":"- 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 [ Time Frame: Up to 490 days ]","definition_or_measurement_approach":"Mean urinary free cortisol (mUFC) ≤ ULN measured at end of IV/SC titration period; Time Frame: up to 490 days."}
• {"endpoint_text":"- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to 1023 days ]","definition_or_measurement_approach":"Count and reporting of treatment-emergent adverse events occurring during study treatment and follow-up; Time Frame: up to 1023 days."}
• {"endpoint_text":"- PK endpoint: Part A Only: Cmax: Maximum Observed Plasma Concentration of Lu AG13909 [ Time Frame: Up to 323 days ]","definition_or_measurement_approach":"Pharmacokinetic measurement of Cmax (maximum observed plasma concentration) for Lu AG13909 in Part A; Time Frame: up to 323 days."}
• {"endpoint_text":"- PK endpoint: Part A Only: Tmax: Nominal Time Corresponding to the Occurrence of Cmax of Lu AG13909 [ Time Frame: Up to 323 days ]","definition_or_measurement_approach":"Pharmacokinetic measurement of Tmax (time to Cmax) for Lu AG13909 in Part A; Time Frame: up to 323 days."}
• {"endpoint_text":"- PK endpoint: Part A & Part B: Ctrough: Minimum Observed Concentration of Lu AG13909 [ Time Frame: Up to 659 days ]","definition_or_measurement_approach":"Pharmacokinetic measurement of Ctrough (minimum observed concentration) at specified times in Parts A and B; Time Frame: up to 659 days."}
• {"endpoint_text":"- PK endpoint: Part A & Part B: Ttrough: Nominal Time Corresponding to the Occurrence of Ctrough [ Time Frame: Up to 659 days ]","definition_or_measurement_approach":"Pharmacokinetic measurement of nominal time corresponding to Ctrough in Parts A and B; Time Frame: up to 659 days."}
• {"endpoint_text":"- PK endpoint: AUC0-tau,ss: Area Under the Plasma Concentration Curve of Lu AG13909 at Steady State [ Time Frame: Up to 1037 days ]","definition_or_measurement_approach":"Pharmacokinetic measurement of AUC0-tau at steady state for Lu AG13909; Time Frame: up to 1037 days."}
• {"endpoint_text":"- PK endpoint: CL: Systemic Clearance of Lu AG13909 [ Time Frame: Up to 1037 days ]","definition_or_measurement_approach":"Pharmacokinetic assessment of systemic clearance (CL) of Lu AG13909; Time Frame: up to 1037 days."}
• {"endpoint_text":"- PK endpoint: t½: Elimination Half-life of Lu AG13909 [ Time Frame: Up to 1037 days ]","definition_or_measurement_approach":"Pharmacokinetic measurement of elimination half-life (t½) of Lu AG13909; Time Frame: up to 1037 days."}
• {"endpoint_text":"- PK endpoint: Vd: Apparent Volume of Distribution of Lu AG13909 [ Time Frame: Up to 1037 days ]","definition_or_measurement_approach":"Pharmacokinetic assessment of apparent volume of distribution (Vd) for Lu AG13909; Time Frame: up to 1037 days."}
• {"endpoint_text":"- PK endpoint: SC Bioavailability (F) of Lu AG13909 [ Time Frame: Up to 1037 days ]","definition_or_measurement_approach":"Assessment of subcutaneous bioavailability (F) of Lu AG13909 compared with IV administration; Time Frame: up to 1037 days."}

Methods

• Study brochure (Part A / Part B and Extension) — country-specific printed materials for potential participants (documents present for HU, IT, RO, PL, FR, ES).
• Participant emails — pre-prepared email communications to potential participants (country-specific versions listed: HU, IT, RO, PL, FR, ES, ES).
• Flyer (blinded) — recruitment flyer materials for outreach (country-specific).
• Entry interview guide and Exit interview guide — standardized scripts/guides for recruitment and exit interviews (country-specific).
• Scout brochure and Scout emails — materials for site scouting/recruitment engagement.
• Pre-ICF phone consent — phone-based pre-consent contact procedure documented.
• Patient card and GP letter — informational materials provided to participants and their GPs.
• Inlay for patients transitioning from Part A to Part B and Visit-by-visit guides — materials to support participant retention and transition.

Hungary

Earliest CTIS Part Ii Submission Date

29-05-2024

Latest Decision Or Authorization Date

10-04-2026

Processing Time Days

681

Number Of Sites

3

Number Of Participants

2

Italy

Earliest CTIS Part Ii Submission Date

11-06-2024

Latest Decision Or Authorization Date

05-03-2026

Processing Time Days

632

Number Of Sites

5

Number Of Participants

2

Romania

Earliest CTIS Part Ii Submission Date

19-04-2024

Latest Decision Or Authorization Date

30-03-2026

Processing Time Days

710

Number Of Sites

3

Number Of Participants

2

Poland

Earliest CTIS Part Ii Submission Date

04-07-2024

Latest Decision Or Authorization Date

07-03-2026

Processing Time Days

611

Number Of Sites

3

Number Of Participants

2

France

Earliest CTIS Part Ii Submission Date

02-07-2024

Latest Decision Or Authorization Date

27-03-2026

Processing Time Days

633

Number Of Sites

6

Number Of Participants

2

Spain

Earliest CTIS Part Ii Submission Date

13-06-2024

Latest Decision Or Authorization Date

01-04-2026

Processing Time Days

657

Number Of Sites

2

Number Of Participants

2

Primary sponsor

Full Name

H. Lundbeck A/S

Organisation Type

Pharmaceutical company

Country Of Registered Address

Denmark

Contract research organisations

Name

ICON Bioanalytical Laboratories

Responsibilities

code 4

Name

Endpoint Clinical Inc.

Responsibilities

code 3

Name

Almac Clinical Services Limited

Responsibilities

IMP packaging tasks

Name

Medidata Solutions International Limited

Responsibilities

eCRF

Name

Celerion Switzerland AG

Responsibilities

code 4

Name

Cerba Research

Responsibilities

code 4

Third parties

• {"country":"United States","full_name":"Tech Observer","duties_or_roles":"Biometric services","organisation_type":"Industry"}
• {"country":"Netherlands","full_name":"ICON Bioanalytical Laboratories","duties_or_roles":"code 4","organisation_type":"Health care"}
• {"country":"Netherlands","full_name":"EuroQol Research Foundation","duties_or_roles":"Paper COA/EQ-5D-5L","organisation_type":"Health care"}
• {"country":"United Kingdom","full_name":"Wythenshawe Hospital","duties_or_roles":"code 4","organisation_type":"Health care"}
• {"country":"United States","full_name":"Modus Outcomes","duties_or_roles":"Entry and exit patient inerview","organisation_type":"Industry"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"Biobanking","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"University Hospital Of Wales","duties_or_roles":"code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Switzerland","full_name":"Celerion Switzerland AG","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Allucent (UK) Limited","duties_or_roles":"code 1; study start-up activities (submissions and contract negotiation)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Medidata Solutions International Limited","duties_or_roles":"eCRF","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Mayo Collaborative Services LLC","duties_or_roles":"Mayo labs is supporting with analysis of  UFC samples for US region","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Almac Clinical Services Limited","duties_or_roles":"IMP packaging tasks","organisation_type":"Industry"}
• {"country":"United States","full_name":"Scarritt Group Inc.","duties_or_roles":"Investigator meeting","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Aktiia SA","duties_or_roles":"Blood pressure measurement","organisation_type":"Industry"}
• {"country":"United Kingdom","full_name":"A4p Consulting Limited","duties_or_roles":"Support with shipment of urine & saliva samples from patient’s home to sites","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Valis Biosciences Inc.","duties_or_roles":"Paper COA/HADS and Cushing QoL","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"Labfish Rental Solutions GmbH","duties_or_roles":"Ancillary supplies (consumables/ equipment) provider","organisation_type":"Industry"}
• {"country":"United States","full_name":"Acolad Life Sciences LLC","duties_or_roles":"Translations Agency","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Cerba Research","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"code 3","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Komtur Pharmaceuticals Iberia S.L.","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}