Clinical trial NCT06471829: A Trial of Lu AG13909 in Adult Participants With Cushing's Disease
Official title: A Phase II, Multi-site, Open-label, Dose-titration Trial to Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Lu AG13909 in Adults With Cushing's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cushing's Disease
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2024-06-24
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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 previous pituitary radiotherapy.

Other protocol-defined criteria apply.

Primary outcomes:
measure: 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
timeFrame: Up to 490 days
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to 1023 days
measure: AUC0-tau,ss: Area Under the Plasma Concentration Curve of Lu AG13909 at Steady State
timeFrame: Up to 1037 days
measure: CL: Systemic Clearance of Lu AG13909
timeFrame: Up to 1037 days
measure: t½: Elimination Half-life of Lu AG13909
timeFrame: Up to 1037 days
measure: Vd: Apparent Volume of Distribution of Lu AG13909
timeFrame: Up to 1037 days
measure: SC Bioavailability (F) of Lu AG13909
timeFrame: Up to 1037 days
measure: Number of Participants With Anti-Drug Antibodies (ADAs)
timeFrame: Up to 1037 days
measure: Part A Only: Cmax: Maximum Observed Plasma Concentration of Lu AG13909
timeFrame: Up to 323 days
measure: Part A Only: Tmax: Nominal Time Corresponding to the Occurrence of Cmax of Lu AG13909
timeFrame: Up to 323 days
measure: Part A & Part B: Ctrough: Minimum Observed Concentration of Lu AG13909
timeFrame: Up to 659 days
measure: Part A & Part B: Ttrough: Nominal Time Corresponding to the Occurrence of Ctrough
timeFrame: Up to 659 days
measure: 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
timeFrame: Up to 491 days
measure: Maintenance of UFC Complete Response (mUFC ≤ULN) at the End of the Part B Maintenance Period
timeFrame: Up to 337 days
measure: Part A and Part B: Percentage Change from Baseline in mUFC at the End of the Titration Period and the Completion Visit
timeFrame: Baseline, up to 561 days
measure: 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
timeFrame: Up to 561 days
measure: 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
timeFrame: Up to 561 days
Other outcomes:
Locations:
city: Bron
country: France
facility: Hopital Louis Pradel
city: Marseille
country: France
facility: Assistance Publique Hopitaux de Marseille (AP-HM) - Hopital La Conception
city: Pessac
country: France
facility: Hopital Haut-Leveque
city: Tbilisi
country: Georgia
facility: Ltd Tbilisi Central Hospital
city: Tbilisi
country: Georgia
facility: National Institute of Endocrinology
city: Tbilisi
country: Georgia
facility: Ltd 'Multiprofile Clinic Consilium Medulla'
city: Tbilisi
country: Georgia
facility: Ltd Aversi Clinic
city: Budapest
country: Hungary
facility: Semmelweis Egyetem, Belgyogyaszati es Onkologiai Klinika
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Rome
country: Italy
facility: Azienda Ospedaliera Universitaria Sant'Andrea
city: Torino
country: Italy
facility: AOU Citta della Salute e della Scienza di Torino
city: Bucharest
country: Romania
facility: Institutul National de Endocrinologie "C.I. Parhon"
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i de Sant Pau
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
Study officials:
References: