A research study of how well macimorelin works to find out if children have a lack of growth hormone and how safe it is

• Register: EUCTR
• Last refreshed on: 8 July 2024
• Main ID: EUCTR2018-001989-42-SI
• Date of registration: 05/05/2021
• Prospective Registration: Yes
• Primary sponsor: Aeterna Zentaris GmbH
• Public title: A research study of how well macimorelin works to find out if children have a lack of growth hormone and how safe it is
• Scientific title: Multicenter, open label trial to investigate the efficacy and safety of a single oral dose of 1.0 mg/kg macimorelin acetate as growth hormone stimulation test (GHST) in pediatric patients with suspected growth hormone deficiency (GHD) - the DETECT Trial
• Date of first enrolment: 05/05/2022
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-001989-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Czechia, Georgia, Germany, Italy, Poland, Romania, Russian Federation, Serbia, Slovakia, Slovenia, Ukraine, United States

Contacts

• Name: Clinical trial information desk
• Affiliation: Aeterna Zentaris GmbH

• Name: Clinical trial information desk
• Affiliation: Aeterna Zentaris GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects are eligible to be included in the trial only if all of the following criteria apply:
1. Informed consent of subject, parent(s) or legally acceptable representative (LAR) of subject and child assent, if appropriate, must be obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
2. Male and female pediatric subjects from 2 to less than 18 years of age at the time of signing informed consent.
3. Indication for the performance of growth hormone stimulation test.
4. Presence of a height measurement minimum 6 and maximum 18 months prior to screening.

Are the trial subjects under 18? yes
Number of subjects for this age range: 100
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects are excluded from the trial if any of the following criteria apply:
Lack of suitability for the trial:
1. Established diagnosis of a disease that is sufficient to explain growth deficiency or metabolic disorders that are also associated with short stature (e.g., Turner syndrome, skeletal dysplasia’s, celiac disease, etc.).
2. Ongoing growth hormone therapy.
3. Presence of hypothyroidism and/or adrenal insufficiency without adequate and stable replacement therapy treatment for at least 30 days prior to first GHST.
4. Treatment with drugs directly affecting the pituitary secretion of somatotropin (e.g., somatostatin analogues, clonidine, levodopa and dopamine agonists) or provoking the release of somatostatin (antimuscarinic agents e.g., atropine).
5. Medical history of ongoing clinically symptomatic psychiatric disorders.
6. 2nd or 3rd degree atrioventricular-block, prolongation of the QRS complex over 120 milliseconds, prolongation of the QTc interval over 450 milliseconds, or any other clinically significant abnormal electrocardiogram results at the screening ECG as judged by the investigator.
7. Previous participation in this trial. Participation is defined as signed informed consent.
8. Participation in any clinical trial of an approved or non-approved investigational medicinal product within 30 days before screening.
Safety concerns:
9. Known or suspected hypersensitivity to trial product(s) or related products;
10. Any disorder, which in the investigator’s opinion might jeopardize subject’s safety or compliance with the protocol.
11. Concomitant treatment with any drugs that might prolong QT/QTc
Note: A subject who receives such treatment will not be a candidate for this study, if his/her condition does not allow for a treatment-free period of at least 5 elimination half-lives of the drug that might prolong QT/QTc before the GHST;
12. Elevation of laboratory parameters indicating hepatic or renal dysfunction or damage (AST, ALT, GGT > 2.5 x ULN; creatinine or bilirubin > 1.5x ULN);
13. Current active malignancy other than non-melanoma skin cancer;
14. Female of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice).
15. Male of reproductive age who or whose partner(s) is not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice).
Administrative reasons:
16. Lack of ability or willingness to give informed consent by the subject and/or his/her legal representative;
17. Anticipated non-availability for trial visits/procedures.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

Diagnosis of growth hormone deficiency in pediatric subjects

Intervention(s)

Trade Name: Macimorelin Consilient Health
Product Name: Macimorelin
Product Code: AEZS-130
Pharmaceutical Form: Granules for oral suspension in sachet
INN or Proposed INN: macimorelin
CAS Number: 945212-59-9
Current Sponsor code: AEZS-130
Other descriptive name: MACIMORELIN ACETATE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.5-

Trade Name: R-Gene 10
Product Name: Arginine Hydrochloride
Product Code: NDC0009-0436-01
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Arginine Hydrochloride
CAS Number: 1119-34-2
Current Sponsor code: Arginine Hydrochloride
Other descriptive name: ARGININE HYDROCHLORIDE
Concentration unit: g/ml gram(s)/millilitre
Concentration type: equal
Concentration number: 0.1-

Trade Name: Catapresan 75
Product Name: Clonidine Hydrochloride
Pharmaceutical Form: Tablet
INN or Proposed INN: Clonidine hydrochloride
CAS Number: 4205-91-8
Current Sponsor code: Clonidine hydrochloride
Other descriptive name: CLONIDINE HYDROCHLORIDE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 75-

Primary Outcome(s)

Secondary Objective: • To assess the agreement of the macimorelin growth hormone stimulation test (GHST) with the outcome of arginine and clonidine GHSTs used in the growth hormone deficiency (GHD) diagnosis in pediatric subjects with suspected GHD;
• To investigate the pharmacodynamics (PD) of macimorelin measured by growth hormone (GH) release and time of the peak concentration;
• To investigate the pharmacokinetics (PK) of macimorelin measured by macimorelin concentration;
• To investigate test-retest reliability;
• To investigate the safety and tolerability of macimorelin as a GHST.
• To investigate on the difference in time parents took off work for macimorelin GHST compared to the standard GHSTs

Timepoint(s) of evaluation of this end point: Derived from Cmax GH measurements collected in the time frame from 0 to 90 minutes after initial macimorelin GHST (visit 2 (day 0)) and GH adjudication status performed by the adjudication committee after visit 4 (between day 11 and day 58)).

Primary end point(s): Area under the Receiver Operator Characteristic curve (ROC AUC) based on GH concentration during growth hormone stimulation test (GHST) following macimorelin administration.

Main Objective: • To determine the diagnostic efficacy of macimorelin in diagnosing suspected growth hormone deficiency (GHD) in pediatric subjects assuming the outcome of GHD status adjudication by the external adjudication committee as the “true” GHD status.

Secondary Outcome(s)

Secondary end point(s): CONFIRMATORY SECONDARY ENDPOINTS
• Sensitivity for the macimorelin GHST
• Specificity for the macimorelin GHST
• Overall agreement between the outcome of the macimorelin GHST and the combined outcome from the 2 standard GHSTs

SUPPORTIVE SECONDARY ENDPOINTS
• Overall agreement between the outcome of the macimorelin GHST and the outcome from each of the 2 standard GHSTs
• Negative predictive value (NPV) and positive predictive value (PPV) for the macimorelin GHST
• Positive agreement and negative agreement between the outcome of the macimorelin GHST and the 2 standard GHSTs
• Overall agreement between the outcome of the first macimorelin GHST and the second macimorelin GHST

PHARMACOKINETICS (PK)
Based on concentration-time profiles of macimorelin: Cmax, Tmax.
PHARMACODYNAMICS (PD)
Based on concentration-time profiles of GH: Cmax GH, Tmax GH.

Timepoint(s) of evaluation of this end point: Sensitivity and Specificity, NPV and PPV for macimorelin GHST: Cmax GH measurements collected in the time frame from 0 to 90 minutes after initial macimorelin GHST (visit 2 (day 0)) and GH adjudication status performed by the adjudication committee after visit 4 (between day 11 and day 58)).

Overall, Positive and Negative agreement between macimorelin GHST and the 2 standard GHSTs: Visit 4 (between day 11 and day 58)

Overall agreement between first and second macimorelin GHST: Visit 5 (between day 19 and day 87)

PK, PD: Cmax and Tmax from 0 to 90 min after a single dose of macimorelin exposure Visit 2 (day 0)

Secondary ID(s)

154015

AEZS-130-P02

Source(s) of Monetary Support

Aeterna Zentaris GmbH

Ethics review

Status: Approved
Approval date: 19/04/2022
Contact: