E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Paediatric Growth Hormone Deficiency |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056438 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To explore the pharmacokinetics and pharmacodynamics of PHA-794428 after single subcutaneous injections in PGHD patients in order to support the development of a PK/PD model in this patient population.
To explore the safety, tolerance and humoral response of PHA-794428 after single subcutaneous injections in PGHD patients. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Male and female children with a minimum age of 6 years.
2. Pre-pubertal as defined by Tanner staging (Tanner JM, 1962).
3. Growth hormone deficiency as defined by GRS Guidelines; GH<8 ng/ml on dynamic testing, together with serum IGF-1 level ≤-1.5 SD. Evidence of severe GHD should be demonstrated by 1 dynamic test if there is supporting pathology, or 2 dynamic tests in the absence of supporting pathology.
4. Growth hormone pre-treatment for at least 6 months prior to the screening visit.
5. Hypopituitary patients must be on adequate hormone replacement therapy.
6. Written informed consent of legally authorized representative (i.e. Parent/Legal Guardian). In addition if possible, assent should be obtained from the child to take part in the study.
7. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests and other procedures.
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E.4 | Principal exclusion criteria |
1. PGHD subjects with uncontrolled pituitary tumor growth. Subjects with pituitary tumors must have demonstrated stable neuro-imaging within the last 12 months of the screening visit.
2. Tumors within 3 mm of the optic chiasm. Subjects with residual pituitary suprasellar disease must be scanned within 3 months of the screening visit.
3. Serum ALT and/or AST ≥ 1.5 times the upper limit of normal range (ULN), or clinically significant hepatic disease.
4. Subjects with diabetes mellitus.
5. Any defined syndrome with short stature
6. Subjects with birth weight and/or birth length ≤ 10th centile.
7. Subjects with body weight below 16 kg.
8. Subjects who have received any experimental drug within the past four months (prior to the first dosing day of the study).
9. Concomitant therapy with other investigational drugs.
10. Subjects with a history of clinically significant allergies, especially drug hypersensitivity.
11. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration, or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the subject inappropriate for entry into this trial.
12. Subjects who, in the opinion of the investigator, are not likely to complete the study for whatever reason. |
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E.5 End points |
E.5.1 | Primary end point(s) |
· Safety and tolerance of a single subcutaneous injection of PHA-794428: Monitoring of AE, safety lab, vital signs, physical examination, body temperature, signs of fluid retention (body weight), reactions at the injection site (Draize scoring and Gracely Box scale).
· Pharmacodynamic effects of PHA-794428 on IGF-1.
· PHA-794428 pharmacokinetics (AUCinf, AUClast, Cmax, Tmax, t1/2) after single subcutaneous injection. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Third party open to study site pharmacist |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |