Clinical Trial Results:
Efficacy and safety of Hemangiol solution in the treatment of high risk infantile hemangioma
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Summary
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EudraCT number |
2014-005555-80 |
Trial protocol |
ES |
Global end of trial date |
21 Feb 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Sep 2017
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First version publication date |
03 Sep 2017
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Other versions |
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Summary report(s) |
CSR Synopsis |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
V00400 SB 3 02
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
PIERRE FABRE DERMATOLOGIE
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Sponsor organisation address |
45 Place Abel Gance, Boulogne-Billancourt, France, 92100
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Public contact |
Clinical Trial Information Desk, PIERRE FABRE DERMATOLOGIE, 34 931850200, contact_essais_cliniques@pierre-fabre.com
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Scientific contact |
Dr Athmane Bouroubi, INSTITUT DE RECHERCHE PIERRE FABRE, 33 534506345, athmane.bouroubi@pierre-fabre.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
21 Feb 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 Feb 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Feb 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To document the efficacy of Hemangiol administered during at least 6 months and upto a maximum of 12 months of age in infants with high risk infantile haemangioma (IH)
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Protection of trial subjects |
The study was conducted in compliance with GCP (CPMP/ICH/135/95), ethical principles that have the origins in the amended version of the Declaration of Helsinki, and all SOPs interne to Pierre Fabre. Trial subjects were infants aged 35 to 142 days (corrected age) at inclusion. The informed consents were obtained from parents prior to screening. The information consent form, in the local language of the 2 participating countries (Spanish in Spain and Polish in Poland), detailled the procedures involved, the aims, methodology, constraints, potential risks to the study subject and the rights of the parents to withdraw consent at any stage or time of the study. The investigators exposed in detail to the parents, in a layman language the what, the why and the how of the study.
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Background therapy |
No other therapies, (other than the subject's usual treatments which do not fall in the non-inclusion criteria defined in the protocol), were administered in the framework of the study. | ||
Evidence for comparator |
This is a single arm, non comparative study carried out in real clinical situation. | ||
Actual start date of recruitment |
29 Jun 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 24
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Country: Number of subjects enrolled |
Spain: 21
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Worldwide total number of subjects |
45
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EEA total number of subjects |
45
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
45
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were recruited within the medical consultations of physicians who are familiar with the management of IH (4 centres in Poland, 6 in Spain): infants with severe IH in proliferative phase, in the age group 25 to 142days (corrected age). The included subjects had to be able to complete the initial treatment period (6 months) before age 1 year | ||||||||||||||
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Pre-assignment
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Screening details |
46 subjects aged, 35 - 150 days (corrected age for premature infants), with high risk IH and, in accordance with Hemangiol SmPC were screened and 45 patients were included in the study. The one patient excluded did not meet the 35 - 150 days age criteria. | ||||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
46 [1] | ||||||||||||||
Number of subjects completed |
45 | ||||||||||||||
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Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Age criteria not met: 1 | ||||||||||||||
| Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 46 patients were screened for enrolment and 45 patients were definitely enrolled in the study as an inclusion criterion was not met for one patient |
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Period 1
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Period 1 title |
Initial Treatment Period
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Hemangiol | ||||||||||||||
Arm description |
- | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
HEMANGIOL
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Investigational medicinal product code |
V00400SB
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Other name |
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Pharmaceutical forms |
Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Dose titration:
1mg/kg/day from Day 1 - 7
2mg/kg/day from Day 8 - 14
3mg/kg/day up to the end of the initial treatment period.
Orally, twice daily (morning and late afternoon) during or straight after a feed.
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Period 2
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Period 2 title |
Follow-up Period
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Is this the baseline period? |
No | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Hemangiol FU | ||||||||||||||
Arm description |
Patients in success at the end of the initial treatment period | ||||||||||||||
Arm type |
No intervention | ||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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| Notes [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: 43 patients completed the initial treatment period but only the patients in success at the end of this period (n=34) entered the follow-up period as per protcocol. |
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Period 3
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Period 3 title |
Retreatment period
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Is this the baseline period? |
No | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Retreatment | ||||||||||||||
Arm description |
Patients in success at the end of the initial treatment period and who had success regression during the follow-up period | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
HEMANGIOL
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Investigational medicinal product code |
V00400SB
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Other name |
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Pharmaceutical forms |
Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Dose titration:
1mg/kg/day from Day 1 - 7 (re-treatment period)
2mg/kg/day from Day 8 - 14 (re-treatment period)
3mg/kg/day up to the end of the re-treatment period.
Orally, twice daily (morning and late afternoon) during or straight after a feed.
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| Notes [3] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: Only 8 of the 34 patients who were in success at the end of the initial treatment period needed to be re-treated in the Investigator's opinion during the follow-up period (success regression) and entered the re-tretreatment period as per protocol. |
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Baseline characteristics reporting groups
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Reporting group title |
Initial Treatment Period
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Hemangiol
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Reporting group description |
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Reporting group title |
Hemangiol FU
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Reporting group description |
Patients in success at the end of the initial treatment period | ||
Reporting group title |
Retreatment
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Reporting group description |
Patients in success at the end of the initial treatment period and who had success regression during the follow-up period | ||
Subject analysis set title |
PP set
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
FAS patients without major deviations or any bias for primary criterion assessment
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End point title |
Primary Criterion - Success rate at the end of the initial treatment period (FAS) [1] | ||||||
End point description |
The primary outcome measure was treatment success at the end of the initial treatment period. Success was determined by the Investigator and was defined as the resolution of the target IH and the absence of functional impact linked to the target IH.
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End point type |
Primary
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End point timeframe |
11 months
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The statistical analysis was purely descriptive with no p value provided as the trial was non comparative for ethical reasons: the primary endpoint was the success rate at the end of the initial treatment period with Hemangiol(R) (after 6 months or until success before one year of age) and this rate was 34/45=75.6% 95% CI [61.7;86.3]. Of note the number of patients in success ("34") is specified in the field labelled "Count". The same has been done for the other efficacy endpoints. |
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| No statistical analyses for this end point | |||||||
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End point title |
Success rate at 6 months (FAS) | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
6 months
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| No statistical analyses for this end point | |||||||
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End point title |
Success rate after re-Initiation of treatment (retreated FAS subset) | ||||||
End point description |
The number (%) of patients in success after re-initiation of treatment in the subset of patients who were in success at the end of the initial treatment period and had a success regression during the follow-up period.
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End point type |
Secondary
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End point timeframe |
6 months
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| No statistical analyses for this end point | |||||||
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End point title |
Primary criterion (PP) | ||||||
End point description |
Number of PP patients in success at the end of the initial treatment period
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End point type |
Other pre-specified
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End point timeframe |
11 months
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| No statistical analyses for this end point | |||||||
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Adverse events information
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Timeframe for reporting adverse events |
Whole study period after first administration (initial treatment period + Follow-up + retreatment)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19
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Reporting groups
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Reporting group title |
Full analysis set
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Reporting group description |
All patients treated | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 4% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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22 Dec 2015 |
Replacement of “relapse” by “success regression” throughout protocol. Success regression, based on the Investigator’s opinion could lead to 3 options: re-initiation, follow-up without re-initiation, withdrawal.
Visits: renumbering of visits as D1, D8 and D15 (instead of D0, D7 and D14).
Instructions to patients: clarification that syringes included in study treatment should be returned to the study centre.
Note: as these above points were mentioned in the information leaflet, an additional information leaflet and corresponding ICF was prepared for signature by all patients’ parents at the time of amendment approval.
Number of patients: clarification that the number of ulcerated IHs (as main severity reason) limited to 2 patients per centre.
Recruitment per centre capped to 8 patients maximum to avoid excessive influence of any given centre. Note: these two criteria were met by the previous 41 patients enrolled under the initial protocol.
Precisions to procedures in case of safety issues at titration and/or in case of lower respiratory tract infection (LRTI):
In case of safety issue at dose increase, the dose could be postponed 2 times/dose (1 week between 2 attempts). If after the third attempt (i.e. 1 initial attempt + 2 additional) the safety issue remains, treatment was definitively stopped and patient withdrawn.
In case of bronchitis or LRTI, treatment was stopped immediately until full recovery. Re-administration did not necessitate an up-titration (i.e. full maintenance dose can be given directly).
BP and HR limits modified to take into account chronological age instead of corrected age. As chronological age may be greater than corrected age, BP and HR limits for age > 150 days were added to the exclusion criteria. Note: as recruitment was nearing completion at the time of the amendment, this change was implemented at statistical analysis. The BP and HR limit modification was with regard to 2 patients born prematurely (chronological age of 191 and 211 |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None | |||
