The following information is fully available at the European Union Clinical Trials Register. Some sections will be here highlighted:
|Full title of the trial||
What does Placebo, Randomized, Double-Blind mean?
Placebo: an inert substance that has no action or effect, but can produce the placebo effect, that is the response that follows the administration of a placebo .
Randomized: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. In this particular case, a placebo will be compared with BMN-111 .
Double-Blind: when the patient and the investigator are blind in knowledge. This means that neither the patient nor the investigator know which patients are getting the drug and which are getting placebo .
|Sponsor’s protocol code number||111-301|
This is the designation of the phase 3
The goal is to test an Investigational medicinal product (IMP)
|The IMP has been designated in this indication as an orphan drug in the Community||Yes|
Any medicinal product that aims to treat a rare disease is designated orphan drug
|Description of the IMP|
|D.3.1||Product name||modified recombinant human C-type natriuretic peptide- CNP|
|D.3.2||Product code||BMN 111|
|D.3.4||Pharmaceutical form||Lyophilisate for solution for injection|
|D.3.4.1||Specific paediatric formulation||Yes|
|D.3.7||Routes of administration for this IMP||Subcutaneous use|
CNP, is expressed as a 126–amino acid protein precursor (preproCNP), and is then processed to an active 53–amino acid cyclic peptide and further processed to a 22–amino acid peptide. Native CNP (CNP22) has a short half-life inside the body of less than 2 minutes in mice and humans. BioMarin modified this CNP for a 39–amino acid CNP variant (BMN 111) and is produced in the bacteria Escherichia coli .
|D.8.1||Is a Placebo used in this Trial?||Yes|
|D.8.3||Pharmaceutical form of the placebo||Lyophilisate and solvent for solution for injection|
|D.8.4||Route of administration of the placebo||Subcutaneous use|
|E.2 Objective of the trial|
|E.2.1||Main objective of the trial||
|E.2.2||Secondary objectives of the trial||
This study will take 1 year to produce results. Upper:lower segment body ratio will be evaluated.
Upper to lower body ratio
The lower body segment is the measurement of the length from the pubic symphysis (roughly the pubic bone) to the floor; the upper body segment is the height minus the lower body segment. The average U/L ratio (upper body segment : lower body segment) at birth is about 1.7; at age 3 years it is 1.3; at greater than 7 years, it is 1.0 with the upper body segment and lower body segment being about equal. Higher U/L ratios are noted in short-limb dwarfism.
So the ideal is a ratio near 1.
|Principal inclusion criteria||
All children that participate in this phase 3 study (111-301) have to first take, the natural history/growth assessment study (111-901) for at least 6 months.
|E.5.1||Primary end point(s)||
|E.5.1.1||Timepoint(s) of evaluation of this end point||
|E.5.2||Secondary end point(s)||
|E.5.2.1||Timepoint(s) of evaluation of this end point||
Endpoint: In clinical trials, it is an event or outcome that can be measured objectively to determine whether the intervention being studied is beneficial. The endpoints of a clinical trial are usually included in the study objectives.
Anthropometric measurements: systematic measurements of the size, shape and composition of the body
PK: Pharmacokinetics is the study of ‘what the body does to the drug’ and includes:
• the rate and extent to which drugs are absorbed into the body and distributed to the body tissues
• the rate and pathways by which drugs are eliminated from the body by metabolism and excretion
• the relationship between time and plasma drug concentration .
|E.8.5||The trial involves multiple Member States||Yes|
|E.8.5.1||Number of sites anticipated in the EEA – Europe||10|
|E.8E.8.6 Trial involving sites outside the EEA.||
|E.8.7||Trial has a data monitoring committee – Yes|
|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 – LVLS|
LVLS – Last visit, last subject/patient
|F. Population of Trial Subjects- Age Range|
|F.1.1||Trial has subjects under 18||Yes|
|F.1.1||Number of subjects for this age range (all world):||110|
|F.1.1.2||Preterm newborn infants (up to gestational age < 37 weeks)||No|
|F.1.1.3||Newborns (0-27 days)||No|
|F.1.1.4||Infants and toddlers (28 days-23 months)||No|
|F.220.127.116.11||Number of subjects for this age range:||88|
|F.1.1.6||Adolescents (12-17 years)||Yes|
|F.18.104.22.168||Number of subjects for this age range:||22|
|F.1.2||Adults (18-64 years)||No|
|F.1.3||Elderly (>=65 years)||No|
|F.4.2||For a multinational trial|
|F.4.2.1||In the EEA||24|
|F.4.2.2||In the whole clinical trial||110|
|F.5||Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)||
- Gupta U, Verma M. Placebo in clinical trials. Perspect Clin Res. 2013 Jan-Mar; 4(1): 49–52
- National Cancer Institute dictionary
- Misra S. Randomized double blind placebo control studies, the “Gold Standard” in intervention based studies. Indian J Sex Transm Dis. 2012 Jul-Dec; 33(2): 131–134.
- US national library of medicine
- IUPHAR Pharmacology Education Project
- EU Clinical Trials Register