Clinical Trial Results:
An open-label, prospective, single-centre, phase II study to assess dose and dose interval requirements with respect to efficacy and safety of AOP2014, PEG-Proline-Interferon alpha-2b, in patients with primary myelofibrosis (grade MF-0 and MF-1)
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Summary
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EudraCT number |
2014-001367-13 |
Trial protocol |
AT |
Global end of trial date |
24 Apr 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
16 Apr 2023
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First version publication date |
16 Apr 2023
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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 |
IASO_MF
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Medical University of Vienna
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Sponsor organisation address |
Waehringer Guertel 18-20, Vienna, Austria,
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Public contact |
Medical University of Vienna, AOP ORPHAN PHARMACEUTICALS AG, sanda.sturlan@aoporphan.com
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Scientific contact |
Medical University of Vienna, AOP ORPHAN PHARMACEUTICALS AG, sanda.sturlan@aoporphan.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 |
11 Oct 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
11 Oct 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
24 Apr 2019
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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 evaluate the efficacy of novel Pegylated-Pro Interferon α-2b formulation in terms of response rate in both, Interferon naive and pretreated patients with early primary myelofibrosis (MF-0 to MF-1).
The favourable pharmacokinetic profile of AOP2014 suggests possible dose reduction and/or treatment interval prolongation options, which, at preserved efficacy, may improve the tolerability of IFN α treatment.
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Protection of trial subjects |
AOP2014 belongs to the interferon substance class that is effectively able to suppress the malignant of myeloid precursor cells and subsequently is expected to possibly adjourn or avoid long term sequel to thrombosis, transformation into overt myelofibrosis and transformation into acute leukemia. The tolerability of peg-IFN-α-2b might potentially have a positive impact on reducing the drop-out rate compared to conventional IFNs. It’s expected that the reduced administration frequency of peg-IFN-α-2b will contribute to higher compliance rates.
The safety profile of interferon alpha is well characterised after clinical experience for nearly 20 years. No additional new adverse drug reactions are expected using this third generation of interferon alpha. It is an effective drug for treating PV with acceptable toxicity28. Since the dose is carefully titrated to the optimal effective dose, no additional risks for the patients are expected.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
04 Aug 2014
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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 |
Austria: 25
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Worldwide total number of subjects |
25
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EEA total number of subjects |
25
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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) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
7
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From 65 to 84 years |
18
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients where eligible to enter the study if they had a confirmed diagnosis of primary myelofibrosis (grade MF-0 and MF-1) according to the 2008 WHO criteria. This included either newly diagnosed Interferon naive patients or patients pre-treated with Pegasys® or PegIntron®, who had stable disease for the previous 3 months. | |||||||||
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Pre-assignment
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Screening details |
Written informed consent; Patients age ≥18 years; Confirmed diagnosis of primary myelofibrosis (grade MF-0 and MF-1) ; patients of childbearing potential need a negative pregnancy test; ECOG ≤ 2 | |||||||||
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Period 1
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Period 1 title |
Study period overall (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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pre-treated | |||||||||
Arm description |
The initial dose of AOP2014 applied to Interferon pre-treated patients will be determined for each patient individually and it will depend of his/her current treatment dose of either Pegasys® or PegIntron. The dose of AOP2014 will be calculated according to the formula: AOP2014 (µg) = Patient’s current treatment dose Pegasys® /PegIntron® (µg)* 0.7. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
AOP2014
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
The initial dose of AOP2014 applied to Interferon pre-treated patients will be determined for each patient individually and it will depend of his/her current treatment dose of either Pegasys® or PegIntron. The dose of AOP2014 will be calculated according to the formula:
AOP2014 (µg) = Patient’s current treatment dose Pegasys® /PegIntron® (µg)* 0.7.
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Arm title
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treatment-naive | |||||||||
Arm description |
In Interferon-naïve patients the initial dose will be calculated as follows: AOP2014 (µg) = Clinically reasoned dose Pegasys® (µg)* 0.7, where Clinically reasoned dose of Pegasys® will depend on the patient’s clinical status and it will be determined individually as if the patient was treated with Pegasys®. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
AOP2014
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
In Interferon-naïve patients the initial dose will be calculated as follows:
AOP2014 (µg) = Clinically reasoned dose Pegasys® (µg)* 0.7,
where Clinically reasoned dose of Pegasys® will depend on the patient’s clinical status and it will be determined individually as if the patient was treated with Pegasys®.
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Baseline characteristics reporting groups
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Reporting group title |
pre-treated
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Reporting group description |
The initial dose of AOP2014 applied to Interferon pre-treated patients will be determined for each patient individually and it will depend of his/her current treatment dose of either Pegasys® or PegIntron. The dose of AOP2014 will be calculated according to the formula: AOP2014 (µg) = Patient’s current treatment dose Pegasys® /PegIntron® (µg)* 0.7. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
treatment-naive
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Reporting group description |
In Interferon-naïve patients the initial dose will be calculated as follows: AOP2014 (µg) = Clinically reasoned dose Pegasys® (µg)* 0.7, where Clinically reasoned dose of Pegasys® will depend on the patient’s clinical status and it will be determined individually as if the patient was treated with Pegasys®. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Erythrocytes, T/l; pre-treated
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
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Subject analysis set title |
Erythrocytes, T/l; treatment-naive
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
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Subject analysis set title |
Hemoglobin, g/dl; pre-treated
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
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Subject analysis set title |
Hemoglobin, g/dl; treatment-naive
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
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Subject analysis set title |
Leukocytes, G/l; pre-treated
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
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Subject analysis set title |
Leukocytes, G/l; treatment-naive (N=16)
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
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Subject analysis set title |
Thrombocytes, G/l; pre-treated
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
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||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Thrombocytes, G/l; treatment-naive
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
LDH, U/l; pre-treated
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
LDH, U/l; treatment-naive
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
ANC, K/µl; pre-treated
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
ANC, K/µl; treatment-naive
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Spleen size, cm; pre-treated
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Spleen size, cm; treatment-naive
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
pre-treated
|
||
Reporting group description |
The initial dose of AOP2014 applied to Interferon pre-treated patients will be determined for each patient individually and it will depend of his/her current treatment dose of either Pegasys® or PegIntron. The dose of AOP2014 will be calculated according to the formula: AOP2014 (µg) = Patient’s current treatment dose Pegasys® /PegIntron® (µg)* 0.7. | ||
Reporting group title |
treatment-naive
|
||
Reporting group description |
In Interferon-naïve patients the initial dose will be calculated as follows: AOP2014 (µg) = Clinically reasoned dose Pegasys® (µg)* 0.7, where Clinically reasoned dose of Pegasys® will depend on the patient’s clinical status and it will be determined individually as if the patient was treated with Pegasys®. | ||
Subject analysis set title |
Erythrocytes, T/l; pre-treated
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||
Subject analysis set title |
Erythrocytes, T/l; treatment-naive
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||
Subject analysis set title |
Hemoglobin, g/dl; pre-treated
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||
Subject analysis set title |
Hemoglobin, g/dl; treatment-naive
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||
Subject analysis set title |
Leukocytes, G/l; pre-treated
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||
Subject analysis set title |
Leukocytes, G/l; treatment-naive (N=16)
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||
Subject analysis set title |
Thrombocytes, G/l; pre-treated
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||
Subject analysis set title |
Thrombocytes, G/l; treatment-naive
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||
Subject analysis set title |
LDH, U/l; pre-treated
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||
Subject analysis set title |
LDH, U/l; treatment-naive
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||
Subject analysis set title |
ANC, K/µl; pre-treated
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||
Subject analysis set title |
ANC, K/µl; treatment-naive
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||
Subject analysis set title |
Spleen size, cm; pre-treated
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||
Subject analysis set title |
Spleen size, cm; treatment-naive
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglobin and LDH values, no statistically significant difference could be found, which can be explained by the cytoreductive effect of previous intereron treatments.
|
||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Patient characteristics after 6 months | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
6 months
|
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|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
Patient characteristics after 6 months | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
For this analysis, patient data were evaluated after the first 6 months of therapy. Descriptive statistics are used to present data on clinical parameters. Since the study cohort comprised of patients who were previously treated with an interferon compound as well as patients who had not received an interferon yet, these two groups are used for comparative investigations. Statistically, the two groups did not differ. Although treatment-naive patients tended to present higher thrombocyte, hemoglo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Comparison groups |
Erythrocytes, T/l; pre-treated v Erythrocytes, T/l; treatment-naive
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
25
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
P-value |
= 0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Method |
PEG-P-IFN α-2b | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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Adverse events information [1]
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Timeframe for reporting adverse events |
No information about AE grading is stated, as the data was insufficient to perform any meaningful evaluation.
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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 |
22.1
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| Frequency threshold for reporting non-serious adverse events: 0% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: All adverse effects which occurred in the first six months of treatment are summarized in table 6. Generally, pre-treated patients suffered from fewer side effects than treatment-naïve patients in every category. This may be due to the fact that pre-treated patients had already been exposed to an interferon in previous treatment regimen whereas treatment-naïve patients had not. No information about AE grading is stated, as the data was insufficient to perform any meaningful evaluation. |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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 | |||
