Clinical Trial Results:
CLINICAL PHASE III STUDY TO EVALUATE THE PHARMACOKINETICS, EFFICACY, TOLERABILITY AND SAFETY OF SUBCUTANEOUS HUMAN IMMUNOGLOBULIN
(OCTANORM 16.5%) IN PATIENTS WITH PRIMARY IMMUNODEFICIENCY DISEASES
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Summary
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EudraCT number |
2013-003877-87 |
Trial protocol |
CZ HU PL SK |
Global end of trial date |
09 Jun 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
07 Apr 2021
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First version publication date |
07 Apr 2021
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Other versions |
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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 |
SCGAM-01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01888484 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Octapharma Pharmazeutika Produktionsges.m.b.H.
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Sponsor organisation address |
Oberlaaer Strasse 235, Vienna, Austria, 1100
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Public contact |
clinical.department@octapharma.com, Octapharma Pharmazeutika Prod.Ges.m.b.H, +43 1610320 , clinical.department@octapharma.com
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Scientific contact |
clinical.department@octapharma.com, Octapharma Pharmazeutika Prod.Ges.m.b.H, +43 1610320, clinical.department@octapharma.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 |
04 Dec 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Jun 2020
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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 |
The first primary objective of the study is to assess the efficacy of octanorm in preventing serious bacterial infections compared with historical control data.
The second primary objective is to evaluate the pharmacokinetic characteristics of octanorm and to compare the area under the curve (AUC) with that of IVIG.
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Protection of trial subjects |
This trial was conducted in accordance to the principles of ICH- GCP, ensuring that the rights, safety and well-being of patients are protected and in consistency with the Declaration of Helsinki and national regulatory requirements. Inclusion and exclusion criteria were carefully defined in order to protect subjects from contraindications, interactions with other medication and risk factors associated with the investigational medicinal product.
Study safety was assessed such as monitoring of AEs and SAEs, monitoring of local injection site reactions, concomitant medication, physical examination, vital signs and safety lab parameters.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
27 May 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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: 11
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Country: Number of subjects enrolled |
Slovakia: 5
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Country: Number of subjects enrolled |
Czechia: 11
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Country: Number of subjects enrolled |
Hungary: 3
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Country: Number of subjects enrolled |
United States: 32
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Country: Number of subjects enrolled |
Canada: 3
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Country: Number of subjects enrolled |
Russian Federation: 10
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Worldwide total number of subjects |
75
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EEA total number of subjects |
30
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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) |
0
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Children (2-11 years) |
26
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Adolescents (12-17 years) |
12
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Adults (18-64 years) |
35
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||
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Pre-assignment
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Screening details |
Patients with documented diagnosis primary immunodeficiency diseases as defined by the European Society for Immunodeficiencies (ESID) and Pan-American Group for Immunodeficiency and requiring immunoglobulin replacement therapy due to hypogammaglobulinaemia or agammaglobulinaemia were screened according to predefined in- and exclusion criteria. | ||||||||||||
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Period 1
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Period 1 title |
Overall Trial (overall 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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Octanorm | ||||||||||||
Arm description |
Octanorm 16.5%, human normal immunoglobulin for weekly (±2 days) subcutaneous (SC) administration. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Octanorm 16.5%
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Octanorm, a human normal immunoglobulin, had to be administered subcutaneously every week (±2 days). A minimum time of 4 days had to be kept in between two single SC infusions.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Octanorm
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Reporting group description |
Octanorm 16.5%, human normal immunoglobulin for weekly (±2 days) subcutaneous (SC) administration. | ||
Subject analysis set title |
Full analysis set (FAS)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The FAS is defined according to the intention-to-treat principle and consists of all patients of the Safety Analysis Set who satisfy all major eligibility criteria and for whom any post‐baseline data are available; it is the set of eligible patients with treatment effects measured.
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Subject analysis set title |
Per Protocol (PP)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The per-protocol (PP) set consists of all patients of the FAS excluding those with major protocol violations which may have an impact on the analysis of the primary efficacy endpoint. This is the set of patients who participated in the study as intended and for whom the primary efficacy endpoint can be evaluated as planned.
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Subject analysis set title |
PK Set
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Patients who had a full PK profile after the last administration of the previously used IVIG product before he was switched to octanorm (PKIV), a full PK profile at the end of the wash-in/wash-out phase (PKSC1) and a final PK profile after 28 administrations of octanorm (at steady state) to assess the bioavailability of total IgG with respect to the two administration methods (PKSC2).
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End point title |
Primary Efficacy Endpoint: Rate of Serious Bacterial Infections per person-year on treatment. [1] | ||||||||||||
End point description |
The primary efficacy endpoint is the rate of SBI (defined as bacteremia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess) per person-year on treatment.
No SBIs were observed during the study. For this reason, it was not possible to calculate a CI using the originally planned compound Poisson process model. In the alternative analysis of CIs based on the standard Poisson distribution, overall the upper limit of the 2- sided 98% CI was 0.065 in the primary observation period and 0.054 in the total treatment period in both the FAS and PP analysis set.
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End point type |
Primary
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End point timeframe |
Baseline to end of the study. (Every 4 weeks until the final evaluation at week 65)
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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 system does not permit reporting of statistical analyses for studies with only 1 arm/reporting group. Therefore, only results for this endpoint are provided. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Primary Pharmacokinetic Endpoint: AUCτ at Steady-State Conditions [2] | ||||||||
End point description |
The AUCτ (i.e., AUC from time 0 (start of the infusion) to the end of the nominal dosing period, standardised to 1 week) at PKSC2 (steady-state conditions) In several cases, AUCτ could not be calculated due to very flat time-concentration profiles.
Geometric mean was 2166.13 h*g/L.
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End point type |
Primary
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End point timeframe |
AUC from time 0 (start of the infusion) to the end of the nominal dosing period. Measured at Week 12 and Week 28.
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| Notes [2] - 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 system does not permit reporting of statistical analyses for studies with only 1 arm/reporting group. Therefore, only results for this endpoint are provided. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Total number (rate) of infections per person-year | ||||||||||
End point description |
The annual rate of all infections of any kind or seriousness.
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End point type |
Secondary
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End point timeframe |
Baseline to end of the study, up to 65 weeks
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| No statistical analyses for this end point | |||||||||||
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End point title |
Non-serious Infections | ||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Up to 65 weeks
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Cmax of Total IgG and IgG Subclasses | ||||||||||||||||||
End point description |
Cmax of Total IgG and IgG Subclasses
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End point type |
Secondary
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End point timeframe |
Up to 28 days
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Tmax of Total IgG and IgG Subclasses | ||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Up to 28 days
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
AUC of Total IgG and IgG Subclasses | ||||||||||||||||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Up to 28 days
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||
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End point title |
Trough Levels of Serum IgG | ||||||||||||||||||
End point description |
Trough levels of serum IgG, IgG1, IgG2, IgG3, IgG4 at PK 7 days after 28th infusion of octanorm.
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End point type |
Secondary
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End point timeframe |
Up to 65 weeks
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
IVIG to Octanorm DCF (Based on the Area Under the Concentration-time Curve [AUCτ]) | ||||||||
End point description |
IVIG to octanorm Dose Conversion Factor (based on the area under the concentration-time curve [AUCτ]) - Regression Model without Restriction.
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End point type |
Secondary
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End point timeframe |
Up to 29 weeks
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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 |
Throughout the whole study from Visit 1 up to Visit 22 (Termination visit)
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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 |
16.0
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Reporting groups
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Reporting group title |
Safety Population (SAF)
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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16 Sep 2015 |
Protocol Version 7: incorporates the change of the maximal number of patients in the age group ≥16 years: amended from 28 to a maximum of 39. In the PK substudy, the number of enrolled patients was changed from 24 to maximum of 34 patients.
Exclusion criterion no. 3 was amended allowing the upper level of the BMI to be <40 (previously BMI ≤30).
The method of subcutaneous administration for adult patients was amended: increase of maximal volume to 40 mL per site, and the total flow rate of max. 100mL per hour together for all sites after the 40th s.c. administration. |
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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 reported | |||
