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

Overview

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

• Drug Lu AG13909
  Solution for injection/infusion

Primary outcome measures

• 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]

Secondary outcome measures (12)

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

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 pituitary radiotherapy within the last 10 years.

Other protocol-defined criteria apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

France · 6 centers

• 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

Italy · 5 centers

• 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

Georgia · 4 centers

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

Hungary · 3 centers

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

Romania · 3 centers

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

Spain · 2 centers

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

United Kingdom · 2 centers

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

United States · 1 center

• University of Michigan — Ann Arbor

Poland · 1 center

• University Hospital in Krakow — Krakow

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗