Clinical trial NCT05669950: A Trial of Lu AG13909 in Participants With Congenital Adrenal Hyperplasia
Official title: A Multi-site, Open-label, Sequential-group, Multiple-dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of Lu AG13909 in Participants With Congenital Adrenal Hyperplasia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Congenital Adrenal Hyperplasia
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2023-01-03
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This trial will evaluate the effects of different doses of Lu AG13909 in adult participants with congenital adrenal hyperplasia, also called CAH. CAH is a rare genetic disorder that affects a person's ability to produce certain hormones. The main goals of this trial are to learn about the safety and tolerability of Lu AG13909, how Lu AG13909 behaves in the body, and how the body responds to Lu AG13909.


Eligibility criteria: Inclusion Criteria:

Parts A and B:

* Confirmed diagnosis of 21-hydroxylase deficiency CAH (based on a pathogenic CYP21A2 variant and/or elevated 17-OHP).
* Morning (pre-glucocorticoid \[GC\] replacement dose) blood concentrations of 17-OHP \>4-times upper limit of normal (ULN).
* Body mass index (BMI) ≥18.5 kilograms (kg)/square meter (m\^2) (minimum 50 kg) and ≤40 kg/m\^2.
* Stable GC replacement therapy for ≥1 month prior to the Screening Visit.
* For the salt-wasting form of CAH, the participant must have been on a stable dose of mineralocorticoid replacement for ≥3 months prior to the Screening Visit.
* Apart from CAH, the participant is generally healthy in the opinion of the investigator and based on medical history, physical examination, vital signs, ECGs, and the results of the safety laboratory tests.

Part C:

* Confirmed diagnosis of 21-hydroxylase deficiency CAH (based on a pathogenic CYP21A2 variant and/or elevated 17-OHP).
* For Cohort C1 only: Morning (pre-GC replacement dose) blood concentrations of androgens (A4) \> ULN for age and sex.
* For Cohort C2 only: Morning (pre-GC replacement dose) blood concentrations of androgens (A4) ≤ ULN for age and sex and the participant is treated with high doses of GC.
* Stable GC replacement therapy for ≥1 month prior to the Screening Visit.
* For the salt-wasting form of CAH, the participant must have been on a stable dose of mineralocorticoid replacement for ≥1 month prior to the Screening Visit.

Exclusion Criteria:

* The participant is pregnant or breastfeeding.
* The participant has a clinically significant abnormal laboratory value, electrocardiogram (ECG) parameter, or vital signs value, or other safety findings at the Screening Visit that indicate a potential risk for the participant if enrolled, in the opinion of the investigator.
* The participant has a history of known hypersensitivity or intolerance to Lu AG13909 or its excipients.

Part C Only:

* The participant has received at least one dose of Lu AG13909 in Part A or Part B.

Other inclusion and exclusion criteria may apply.

Primary outcomes:
measure: Parts A and B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to Day 161
measure: Parts A and B: Number of Participants With Anti-Drug Antibodies (ADAs)
timeFrame: Day 1 up to Day 161
measure: Parts A and B: Cmax: Maximum Observed Serum Concentration of Lu AG13909
timeFrame: 0 (predose) up to 24 hours postdose on Day 1 to Day 161
measure: Parts A and B: Tmax: Nominal Time Corresponding to the Occurrence of Cmax
timeFrame: 0 (predose) up to 24 hours postdose on Day 1 to Day 161
measure: Parts A and B: Ctrough: Minimum Observed Serum Concentration of Lu AG13909
timeFrame: 0 (predose) up to 24 hours postdose on Day 1 to Day 161
measure: Parts A and B: t½: Apparent Elimination Half-life of Lu AG13909
timeFrame: 0 (predose) up to 24 hours postdose on Day 1 to Day 161
measure: Parts A and B: AUC0-infinity: Area under the plasma concentration curve of x from zero to infinity of Lu AG13909
timeFrame: 0 (predose) up to 24 hours postdose on Day 1 to Day 161
measure: Parts A and B: CL: Apparent Total Serum Clearance of Lu AG13909
timeFrame: 0 (predose) up to 24 hours postdose on Day 1 to Day 161
measure: Parts A and B: Vz: Volume of Distribution During the Terminal Elimination Phase After IV Administration of Lu AG13909
timeFrame: 0 (predose) up to 24 hours postdose on Day 1 to Day 161
measure: Parts A and B: Change From Baseline After Each Dose of Lu AG13909 in Blood Concentrations of 17-hydroxyprogesterone (17-OHP) and Androstenedione (A4)
timeFrame: Baseline up to Day 85
measure: Parts A and B: AUC0-tau: Area under the curve over a dosing interval
timeFrame: 0 (predose) up to 24 hours postdose on Day 1 to Day 161
measure: Part C: Morning Concentration of A4 in Blood <Upper Limit of Normal (ULN)
timeFrame: Day 169
Secondary outcomes:
measure: Part C: Lu AG13909 Serum Concentrations Following Multiple IV Doses
timeFrame: Baseline up to Day 352
measure: Part C: Change From Baseline of Lu AG13909 in Blood Concentrations of 17-OHP and A4
timeFrame: Baseline up to Day 169
measure: Part C: Number of Participants With TEAEs
timeFrame: Baseline up to Day 352
measure: Part C: Number of Participants With ADAs
timeFrame: Baseline up to Day 352
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
city: Huddinge
country: Sweden
facility: Karolinska University Hospital/ Huddinge
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
Study officials:
References: