Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Macimorelin · 3 trials · 3 indications
Assuming the outcome of GHD status adjudication final clinical diagnosis as the "true" GHD status, the diagnostic efficacy (estimated sensitivity, specificity, misclassification) of the macimorelin GHST will be based on the area under the receiver operating characteristic curve (ROC AUC).
In the primary efficacy analysis, the estimated percentages of the agreements and the two-sided 95% confidence interval (or one-sided 97.5% confidence interval) of the percent agreement based on Clopper-Pearson are presented. The probability for a "Negative Agreement" equals the sum of the probability of both tests being correct (negative test results for both tests for subjects with "true non-AGHD") and the probability of both tests being wrong (negative test results for both tests for subjects with "true AGHD"). The performance of the GHST with Macimorelin was considered to be acceptable if the lower bound of the two-sided 95% confidence interval (or lower bound of the one-sided 97.5% confidence interval) for the primary efficacy variables was 75% or higher for 'percent negative agreement', and 70% or higher for the 'percent positive agreement'. The following cut-off values for stimulated GH levels were used: - MAC: GH: 2.8 ng/mL, - ITT: GH: 5.1 ng/mL.
The change of body weight(kg)will be measured between day 1 and day (Day 7-Day 1).
The change of IGF-1 plasma levels will be measured between day 1 (prior to dosing) and day 7.
The change of quality of life score (Anderson Symptom Assessment Scale \[ASAS; absolute score\], Functional Assessment of Chronic Illness-Fatigue \[FACIT-F; total score\]) will be measured between day 1 and day 7. The ASAS is a validated measure of quality of life (QOL) associated with symptom clusters commonly seen in cancer patient populations. The absolute score ranges from 0-100 with higher scores indicative of worse cancer symptoms. The FACIT-F is a validated measure of QOL associated with fatigue related to chronic illness. To account for missing items, the FACIT-F total score (sum of subscales) was adjusted by calculating the percent total score of items completed with the following: (FACIT-F Total Score)/(N items completed ×4 (maximum possible score for each item ) × 100% Scores range from 0 to 160 with higher scores indicative of greater fatigue. Tests consists of 5 subscales: Physical, Social/Family, Emotional, and Functional Well-Being, and Additional Concerns.
| Arm | Type | Description |
|---|---|---|
| standard GHST order randomized: arginine - clonidine | ACTIVE_COMPARATOR | At visit 2 (V2), all subjects will perform the macimorelin GHST and will be randomized 1:1 to the order of the clonidine and arginine GHSTs at visit 3 (V3) and visit 4 (V4). In this arm, those subjects will be presented which will have been randomized to the arginine GHST at V3 and the clonidine GHST at V4. At visit 5 (V5) all subjects will perform the macimorelin GHST. |
| standard GHST order randomized: clonidine - arginine | ACTIVE_COMPARATOR | At V2, all subjects will perform the macimorelin GHST and will be randomized 1:1 to the order of the clonidine and arginine GHSTs at V3 and V4. In this arm, those subjects will be presented which will have been randomized to the clonidine GHST at V3 and to the arginine GHST at V4. At V5 all subjects will perform the macimorelin GHST. |
| GHST Sequence A | EXPERIMENTAL | 1st Macimorelin-GHST, 2nd Insulin Tolerance Test |
| GHST Sequence B | EXPERIMENTAL | 1st Insulin Tolerance Test, 2nd Macimorelin-GHST |
| Macimorelin | ACTIVE_COMPARATOR | - |
| Placebo | PLACEBO_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| Macimorelin | DRUG | Dosage form: granules for oral solution, Dosage: 1.0 mg/kg body weight, Frequency and duration: single oral dose administration. Macimorelin will be supplied in single-use aluminum pouches (synonymous: sachets) each containing 63.6 mg macimorelin as acetate, which provide 0.5 mg/mL of macimorelin when dissolved in 120 mL of water. The excess amount of 3.6 mg represents an overfill, which is needed to obtain the target concentration. |
| Arginine | DIAGNOSTIC_TEST | For the arginine GHST, R-Gene® 10 from Pfizer will be provided as labelled investigational medicinal product (IMP). After an overnight fast, soluble arginine hydrochloride (0.5 g/kg) will be given i.v. as an infusion with an infusion duration of 30 min. |
| Clonidine | DIAGNOSTIC_TEST | For the clonidine GHST, CATAPRESAN® 75 tablets (Boehringer Ingelheim) will be provided as labelled IMP. Each tablet contains 75 ug clonidine hydrochloride. The tablets will be provided in boxes containing 10 tablets. The target dose is 0.15 mg/m2 body surface with a dose range of 0.08 - 0.15 mg/m2. Maximum dose will be 0.25 mg. After an overnight fast, clonidine (0.15 mg/m2 body surface) will be given orally. |
| Insulin | DRUG | Insulin, 0.10 U/kg (0.15 U/kg if BMI \> 30 kg/m2), intravenous injection, single dose |
| Placebo | DRUG | placebo (Powerade®) daily for 7 days. |
Inclusion Criteria: 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, includin...
Macimorelin is used to diagnose growth hormone deficiency, including in adults with pituitary anomalies and in children. It is also being studied in cancer cachexia. It is a small molecule ghrelin receptor agonist developed by COSCIENS Biopharma Inc. (ticker CSCI).
Macimorelin targets the growth hormone secretagogue receptor (GHSR), also known as the ghrelin receptor. It acts as an agonist at this receptor, stimulating growth hormone release. This mechanism underlies its use as a diagnostic test for growth hormone deficiency.
Macimorelin is developed by COSCIENS Biopharma Inc., which trades under the ticker CSCI. The company is responsible for its clinical development and regulatory activities.
Macimorelin has completed Phase 3 trials for growth hormone deficiency and a Phase 2 trial for cancer cachexia. It is an investigational drug still in clinical development. The Phase 2 trial in cancer cachexia has been completed.
Macimorelin has been studied in three completed trials: NCT04786873, a Phase 3 trial in children with growth hormone deficiency; NCT02558829, a Phase 3 validation trial in adults with growth hormone deficiency and pituitary anomalies; and NCT01614990, a Phase 2 pilot trial in cancer cachexia.
Macimorelin is also known by the brand name Macrilen. Both names refer to the same small molecule ghrelin receptor agonist developed by COSCIENS Biopharma Inc. for diagnosing growth hormone deficiency and being studied in cancer cachexia.