Clinical Trial Results:
Prospective, double-blind, randomized, multicenter phase III study evaluating efficacy and safety of three different dosages of NewGam in patients with chronic inflammatory demyelinating poly(radiculo)neuropathy.
Summary
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EudraCT number |
2015-005443-14 |
Trial protocol |
DE DK SE HU CZ PL BG |
Global end of trial date |
05 Sep 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Aug 2020
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First version publication date |
29 Aug 2020
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Other versions |
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 |
NGAM-08
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Additional study identifiers
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ISRCTN number |
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US NCT number |
NCT02638207 | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
IND: 14096 | ||
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 |
Global Clinical Project Manager, Octapharma Pharmazeutika Produktionsges.m.b.H., 43 610321716, clinical.department@octapharma.com
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Scientific contact |
Global Clinical Project Manager, Octapharma Pharmazeutika Produktionsges.m.b.H., 43 610321716, 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 |
31 Jan 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 |
05 Sep 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 |
Primary:
To provide confirmatory data on the effect of 1.0 g/kg NewGam every three weeks in patients with active CIDP based on the percentage of responders at Week 24, which should corroborate the existing evidence on efficacy of IGIV in CIDP as known from published literature.
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Protection of trial subjects |
The study described herein is conducted in accordance with the ethical principles of the Declaration of Helsinki, and ICH-GCP (Note for Guidance CPMP/ICH/135/95), 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.
Throughout the study safety was assessed, such as of monitoring of AEs, SAEs, vital signs and concomitant medication.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Aug 2017
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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 |
Ukraine: 41
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Country: Number of subjects enrolled |
Bulgaria: 4
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Country: Number of subjects enrolled |
Canada: 1
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Country: Number of subjects enrolled |
Czech Republic: 17
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Country: Number of subjects enrolled |
Germany: 2
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Country: Number of subjects enrolled |
Hungary: 2
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Country: Number of subjects enrolled |
Poland: 14
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Country: Number of subjects enrolled |
Romania: 39
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Country: Number of subjects enrolled |
Russian Federation: 22
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Worldwide total number of subjects |
142
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EEA total number of subjects |
78
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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) |
97
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From 65 to 84 years |
45
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Patients with documented diagnosis of chronic inflammatory demyelinating poly(radiculo)neuropathy (ProCID Study) were screened according to predefined in- and exclusion criteria. | ||||||||||||||||||||||||||||||||||||
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 |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor | ||||||||||||||||||||||||||||||||||||
Blinding implementation details |
In the event of medical emergency, the investigator was able to unblind a patient immediately by accessing the IWRS system.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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0.5 g/kg NewGam | ||||||||||||||||||||||||||||||||||||
Arm description |
All patients received a loading dose of 2.0 g/kg Newgam (administered over two consecutive days), followed by seven infusions of the maintenance dose the patient has been randomized to (0.5g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days). | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
NewGam
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Investigational medicinal product code |
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Other name |
Panzyga
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
All patients received a loading dose of 2.0 g/kg NewGam (administered over 2 consecutive days), followed by 7 infusions of the maintenance dose the patient has been randomized to (i.e., 0.5, 1.0 or 2.0 g/kg NewGam), also administered over 2 consecutive days every 3 weeks (±4 days). The same volumes and infusion rates were used regardless of the randomized group, with supplementation with an authorized 0.9% w/v isotonic sodium chloride solution as appropriate to maintain the blinding. There was the option of rescue treatment with two consecutive blinded infusions of 2.0 g/kg NewGam at 3-week intervals (±4 days) for all patients in the 0.5 and 1.0 g/kg NewGam arms who were either stable at Week 6 or deteriorated after Week 3 and before Week 18.
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Arm title
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1.0 g/kg NewGam | ||||||||||||||||||||||||||||||||||||
Arm description |
All patients will receive a loading dose of 2.0 g/kg Newgam (administered over two consecutive days), followed by seven infusions of the maintenance dose the patient has been randomized to (1.0g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days). | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
NewGam
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Investigational medicinal product code |
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Other name |
Panzyga
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
All patients received a loading dose of 2.0 g/kg NewGam (administered over 2 consecutive days), followed by 7 infusions of the maintenance dose the patient has been randomized to (i.e., 0.5, 1.0 or 2.0 g/kg NewGam), also administered over 2 consecutive days every 3 weeks (±4 days). The same volumes and infusion rates were used regardless of the randomized group, with supplementation with an authorized 0.9% w/v isotonic sodium chloride solution as appropriate to maintain the blinding. There was the option of rescue treatment with two consecutive blinded infusions of 2.0 g/kg NewGam at 3-week intervals (±4 days) for all patients in the 0.5 and 1.0 g/kg NewGam arms who were either stable at Week 6 or deteriorated after Week 3 and before Week 18.
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Arm title
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2.0 g/kg NewGam | ||||||||||||||||||||||||||||||||||||
Arm description |
All patients will receive a loading dose of 2.0 g/kg Newgam (administered over two consecutive days), followed by seven infusions of the maintenance dose the patient has been randomized to (2.0g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days). | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
NewGam
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Investigational medicinal product code |
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Other name |
Panzyga
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
All patients received a loading dose of 2.0 g/kg NewGam (administered over 2 consecutive days), followed by 7 infusions of the maintenance dose the patient has been randomized to (i.e., 0.5, 1.0 or 2.0 g/kg NewGam), also administered over 2 consecutive days every 3 weeks (±4 days). The same volumes and infusion rates were used regardless of the randomized group, with supplementation with an authorized 0.9% w/v isotonic sodium chloride solution as appropriate to maintain the blinding. There was the option of rescue treatment with two consecutive blinded infusions of 2.0 g/kg NewGam at 3-week intervals (±4 days) for all patients in the 0.5 and 1.0 g/kg NewGam arms who were either stable at Week 6 or deteriorated after Week 3 and before Week 18.
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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 |
0.5 g/kg NewGam
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Reporting group description |
All patients received a loading dose of 2.0 g/kg Newgam (administered over two consecutive days), followed by seven infusions of the maintenance dose the patient has been randomized to (0.5g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days). | ||
Reporting group title |
1.0 g/kg NewGam
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Reporting group description |
All patients will receive a loading dose of 2.0 g/kg Newgam (administered over two consecutive days), followed by seven infusions of the maintenance dose the patient has been randomized to (1.0g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days). | ||
Reporting group title |
2.0 g/kg NewGam
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Reporting group description |
All patients will receive a loading dose of 2.0 g/kg Newgam (administered over two consecutive days), followed by seven infusions of the maintenance dose the patient has been randomized to (2.0g/kg NewGam), also administered over two consecutive days every 3 weeks (±4 days). |
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End point title |
Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score in the 1.0 g/kg Group [1] | ||||||||||||
End point description |
Efficacy - Proportion of responders in the 1.0 g/kg NewGam arm at Week 24 (Termination Visit) relative to baseline (Week 0). A responder being defined as a patient with a decrease of at least 1 point on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score (a scale from 0 to 10, from healthy to unable to make any purposeful movements with arms and/or legs)
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End point type |
Primary
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End point timeframe |
at week 24
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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: Primary endpoint was evaluated by comparing the lower limit of the 95% Wilson-Score CI for the percentage of responders on the adjusted INCAT disability scale in the 1.0 g/kg dose group with a predefined threshold of 42%. The response rates in the alternative dose groups were compared descriptively to the 1.0 g/kg treatment group, and the CIs for the differences were presented. Descriptive summaries are presented for each of the primary, secondary and exploratory variables. |
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No statistical analyses for this end point |
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End point title |
Decrease in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score in the 0.5 g/kg and 2.0 g/kg Group | ||||||||||||
End point description |
Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 relative to baseline compared to the 1.0 g/kg arm, based on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score.
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End point type |
Secondary
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End point timeframe |
at week 24
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No statistical analyses for this end point |
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End point title |
Grip Strength Score | ||||||||||||
End point description |
Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 relative to Baseline at Week 0 compared to the 1.0 g/kg arm, based on the grip strength (Martin
Vigorimeter) using the previously published minimum clinically important difference (MCID) cut-off of 8 kPa .
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End point type |
Secondary
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End point timeframe |
at Week 24
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No statistical analyses for this end point |
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End point title |
Inflammatory Rasch-built Overall Disability Scale (I-RODS Score) | ||||||||||||
End point description |
Proportion of responders in the 0.5 g/kg and 2.0 g/kg NewGam arms at Week 24 relative to Baseline at Week 0 compared to the 1.0 g/kg arm, based on the I-RODS scores using the
MCID concept related to the varying standard errors (MCID-SE).
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End point type |
Secondary
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End point timeframe |
at Week 24
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No statistical analyses for this end point |
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End point title |
Worsening in the Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score | ||||||||||||
End point description |
Time to first confirmed worsening on the adjusted INCAT disability scale by at least 1 point from the value at Baseline (Week 0)
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End point type |
Secondary
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End point timeframe |
24 weeks
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Notes [2] - No patients with worsening in this group, analysis not possible. [3] - Only 1 patient with worsening thus an analysis of the time to first worsening was not possible. [4] - No patients with worsening in this group, analysis not possible |
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No statistical analyses for this end point |
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End point title |
Mean Change in Grip Strength | ||||||||||||||||||||||||
End point description |
Mean change from baseline (Week 0) to Termination Visit in grip strength of both hands (assessed by Martin vigorimeter).
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End point type |
Secondary
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End point timeframe |
Termination Visit
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No statistical analyses for this end point |
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End point title |
Inflammatory Rasch-built Overall Disability Scale (I-RODS) | ||||||||||||||||
End point description |
Mean change from baseline (Week 0) to Termination Visit in Inflammatory Rasch-built overall disability sum score (I-RODS using the concept of MCID-SE as recently reported) and number of improvers.
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End point type |
Secondary
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End point timeframe |
Termination Visit
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No statistical analyses for this end point |
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End point title |
Motor Nerves | ||||||||||||||||
End point description |
Mean change from baseline (Week 0) to Termination Visit in sum of the distal evoked amplitude of 4 right sided and 4 left sided motor nerves (peroneal, tibial, ulnar and median).
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End point type |
Secondary
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End point timeframe |
Termination Visit
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No statistical analyses for this end point |
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End point title |
Mean Change in Pain Intensity Numerical Rating Scale (PI-NRS Scale) | ||||||||||||||||
End point description |
Mean change from baseline (Week 0) to Termination Visit in Pain Intensity Numeric Rating Scale (PI-NRS)
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End point type |
Secondary
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End point timeframe |
Termination Visit
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No statistical analyses for this end point |
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End point title |
Worsening on the Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale) | ||||||||||||
End point description |
Time to first confirmed worsening on the I-RODS scale.
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End point type |
Secondary
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End point timeframe |
24 weeks
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Notes [5] - Only 1 patient with worsening , thus an analysis of the time to first worsening was not possible. [6] - Only 2 patients with worsening , thus an analysis of the time to first worsening was not possible. [7] - No patients with worsening in this group, analysis not possible. |
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No statistical analyses for this end point |
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End point title |
1 Point Decrease in the INCAT Disability Score | ||||||||||||||||
End point description |
Time to 1 point decrease (improvement of disability) in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score.
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End point type |
Secondary
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End point timeframe |
24 weeks
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No statistical analyses for this end point |
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End point title |
Decrease in Inflammatory Rasch-built Overall Disability Scale (I-RODS Scale) | ||||||||||||||||
End point description |
Time to decrease in Inflammatory Rasch-built overall disability scale (I-RODS) scores.
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End point type |
Secondary
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End point timeframe |
24 weeks
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Notes [8] - No patients with worsening thus an analysis of the time to first worsening was not possible. [9] - Only 1 patient with worsening thus an analysis of the time to first worsening was not possible. [10] - No patients with worsening thus an analysis of the time to first worsening was not possible |
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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 week 0 up to week 24 (end of study visit)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
Safety Population
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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08 Jun 2018 |
Amendment 2:
-addition of an upper limit for age of patients of <80 years to inclusion criteria;
-addition of ‘severe’ to exclusion criterion regarding hypersensitivity to blood products
-material of infusion bags (ethylene vinyl acetate) deleted and period of storage of infusion bags reduced from 72 to 24 hours
-PGIC assessment at Screening deleted
-viral testing added at Visit 2 (in addition to the screening sample) |
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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 |