A Trial of Lu AG13909 in Adult Participants With Cushing's Disease

Официальное название

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

Обзор

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).

Подробное описание

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

Вмешательства

• Препарат Lu AG13909
  Solution for injection/infusion

Первичные конечные точки

• 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 [Срок оценки: Up to 490 days]

Вторичные конечные точки (12)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Срок оценки: Up to 1023 days]
• AUC0-tau,ss: Area Under the Plasma Concentration Curve of Lu AG13909 at Steady State [Срок оценки: Up to 1037 days]
• CL: Systemic Clearance of Lu AG13909 [Срок оценки: Up to 1037 days]
• t½: Elimination Half-life of Lu AG13909 [Срок оценки: Up to 1037 days]
• Vd: Apparent Volume of Distribution of Lu AG13909 [Срок оценки: Up to 1037 days]
• SC Bioavailability (F) of Lu AG13909 [Срок оценки: Up to 1037 days]
• Number of Participants With Anti-Drug Antibodies (ADAs) [Срок оценки: Up to 1037 days]
• Part A Only: Cmax: Maximum Observed Plasma Concentration of Lu AG13909 [Срок оценки: Up to 323 days]
• Part A Only: Tmax: Nominal Time Corresponding to the Occurrence of Cmax of Lu AG13909 [Срок оценки: Up to 323 days]
• Part A & Part B: Ctrough: Minimum Observed Concentration of Lu AG13909 [Срок оценки: Up to 659 days]
• Part A & Part B: Ttrough: Nominal Time Corresponding to the Occurrence of Ctrough [Срок оценки: 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 [Срок оценки: Up to 491 days]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 6 центров

• Centre Hospitalier Universitaire d'Angers — Angers
• Assistance Publique Hopitaux de Marseille (AP-HM) - Hopital La Conception — Marseille
• Hopital Louis Pradel — Bron
• APHP - Hôpital Bicêtre — Le Kremlin-Bicêtre
• Centre Hospitalier Universitaire De Lille — Lille
• Hopital Haut-Leveque — Pessac

Италия · 5 центров

• Azienda Ospedale Università di Padova — Padova
• Azienda Ospedaliero-Universitaria Pisana — Pisa
• Università degli Studi di Messina - Azienda Ospedaliera Universitaria Policlinico 'Gaetano — Messina
• Azienda Ospedaliera Universitaria Sant'Andrea — Rome
• AOU Citta della Salute e della Scienza di Torino — Torino

Грузия · 4 центра

• Ltd Tbilisi Central Hospital — Tbilisi
• National Institute of Endocrinology — Tbilisi
• Multiprofile Clinic Consilium Medulla Ltd — Tbilisi
• Ltd Aversi Clinic — Tbilisi

Венгрия · 3 центра

• Semmelweis Egyetem, Belgyogyaszati es Onkologiai Klinika — Budapest
• Debreceni Egyetem Klinikai Kozpont — Debrecen
• University Hospital of Pecs — Pécs

Румыния · 3 центра

• Institutul National de Endocrinologie "C.I. Parhon" — Bucharest
• Spitalul Clinic Judetean de Urgenta Cluj-Napoca — Clju-Napoca
• Spitalul Clinic Judetean Mures — Mures

Испания · 2 центра

• Hospital de la Santa Creu i de Sant Pau — Barcelona
• Hospital Universitario Ramon y Cajal — Madrid

Великобритания · 2 центра

• Northern Care Alliance, North Manchester General Hospital — Manchester
• University of Birmingham Institute of Metabolism and Systems Research — Birmingham

США · 1 центр

• University of Michigan — Ann Arbor

Польша · 1 центр

• University Hospital in Krakow — Krakow

Идентификаторы

NCT: NCT06471829 · 20433A · 2023-504733-53-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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