A Trial of Lu AG13909 in Adult Participants with Cushing’s Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

H. Lundbeck A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

26 Sep 2024 → ongoing

Decision date (initial)

2024-07-18

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

H. Lundbeck A/S

External identifiers

EU CT number

2023-504733-53-00

ClinicalTrials.gov

NCT06471829

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

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 a) the effect of Lu AG13909 on cortisol levels. b) the safety and tolerability of Lu AG13909 c) the pharmacokinetic parameters of Lu AG13909 (how the drug is absorbed, distributed, and processed by the body).

Conditions and MedDRA coding

Cushing's Disease

Regulatory references

Scientific advice from competent authorities

Danish Health And Medicines Authority, Paul-Ehrlich-Institut, Swedish Medical Products Agency

Plan to share IPD

Yes

IPD plan description

Lundbeck is committed to share the data from this clinical trial when the product is approved in Europe and/or the United States. Please visit www.lundbeck.com for more information about our clinical data sharing policy and processes.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. The participant is a man or woman with a confirmed diagnosis of adrenocorticotropic hormone (ACTH) driven CD of pituitary source as per current guidelines
2. Morning plasma ACTH levels > lower limit of normal (LLN)
3. 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
4. The participant has a 24-hour UFC >1.5 × ULN (the mean of ≥3 days of 24-hour urine collection).
5. 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.
6. 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 7

1. The participant is pregnant, breastfeeding, intends to become pregnant, or is of child-bearing potential and not willing to use adequate contraceptive methods.
2. 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.
3. The participant has a history of known hypersensitivity or intolerance to Lu AG13909 or its excipients.
4. The participant has immediate need for pituitary surgery within 6 months from screening in the opinion of the investigator.
5. 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
6. The participant had pituitary surgery <6 weeks prior to screening.
7. The participant had pituitary radiotherapy within the last 3 years.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 11

1. 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 ]
2. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to 1023 days ]
3. PK endpoint: Part A Only: Cmax: Maximum Observed Plasma Concentration of Lu AG13909 [ Time Frame: Up to 323 days ]
4. PK endpoint: Part A Only: Tmax: Nominal Time Corresponding to the Occurrence of Cmax of Lu AG13909 [ Time Frame: Up to 323 days ]
5. PK endpoint: Part A & Part B: Ctrough: Minimum Observed Concentration of Lu AG13909 [ Time Frame: Up to 659 days ]
6. PK endpoint: Part A & Part B: Ttrough: Nominal Time Corresponding to the Occurrence of Ctrough [ Time Frame: Up to 659 days ]
7. PK endpoint: AUC0-tau,ss: Area Under the Plasma Concentration Curve of Lu AG13909 at Steady State [ Time Frame: Up to 1037 days ]
8. PK endpoint: CL: Systemic Clearance of Lu AG13909 [ Time Frame: Up to 1037 days ]
9. PK endpoint: t½: Elimination Half-life of Lu AG13909 [ Time Frame: Up to 1037 days ]
10. PK endpoint: Vd: Apparent Volume of Distribution of Lu AG13909 [ Time Frame: Up to 1037 days ]
11. PK endpoint: SC Bioavailability (F) of Lu AG13909 [ Time Frame: Up to 1037 days ]

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

H. Lundbeck A/S

Sponsor organisation

H. Lundbeck A/S

Address

Ottiliavej 9

City

Valby

Postcode

2500

Country

Denmark

Scientific contact point

Organisation

H. Lundbeck A/S

Contact name

Clinical Trial Information

Public contact point

Organisation

H. Lundbeck A/S

Contact name

Clinical Trial Information

Third parties 21

Locations

6 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 165 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications