Clinical Trial Results:
An Open Label Randomised Controlled Trial of Mycophenolate Mofetil Versus Cyclophosphamide for the Induction of Remission of Childhood Polyarteritis Nodosa
Summary
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EudraCT number |
2013-004668-71 |
Trial protocol |
GB IT PT ES BE |
Global end of trial date |
26 Jun 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Jan 2021
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First version publication date |
03 Jan 2021
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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 |
11/0499
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
EudraCT: 2013-004668-71 | ||
Sponsors
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Sponsor organisation name |
University College London
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Sponsor organisation address |
Gower Street, London, United Kingdom,
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Public contact |
Professor Paul Brogan, University College London, p.brogan@ucl.ac.uk
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Scientific contact |
Professor Paul Brogan, University College London, p.brogan@ucl.ac.uk
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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 |
24 Aug 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 |
26 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 |
Is mycophenelate mofetil (MMF) as effective as cyclophosphamide (CYC) at inducing remission in children with polyarteritis nodosa (PAN)?
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Protection of trial subjects |
The identification and recruitment of participants to the MYPAN trial and the administration of the trial treatments was carried out by trained health care professionals in a hospital environment following standard, routine procedures. All those who oversaw treatment were trained on the study, evidenced by the collection of site delegation logs. Current CVs and GCP certificates were also obtained for all staff members who had a delegated duty within the study.
All members of site staff who approached the participant’s family for consent were trained on the study and equipped with sufficient knowledge to answer any trial related questions. In addition, these members of staff had the required clinical skills to provide additional support to those families that were emotionally distressed by their child’s condition. Patient data was collected at site using CRFs specifically designed for the MYPAN trial. All collected information was pseudo-anonymised and transferred to the Liverpool Clinical Trials Centre (LCTC) in an agreed secure format. The management of the study was done in line with Ethical, Regulatory and LCTC policies/procedures.
Protocol procedures included mechanisms to manage anticipated adverse reactions due to the established safety profiles of the trial interventions. For example, the trial interventions are immunosuppressants that can be associated with opportunistic infection, and mandatory prophylaxis with cotrimoxazole was required to prevent this occurrence. Other examples of risk mitigation were the prescribing of MMF at half the recommended dose for the first week, thereafter increasing to the full dose in order to mitigate against gastrointestinal adverse effects, and the use of anti-emetics and recommended co-administration of MESNA and adequate hydration as standard for CYC allocated participants.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Aug 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 |
Spain: 1
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Country: Number of subjects enrolled |
United Kingdom: 7
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Country: Number of subjects enrolled |
Turkey: 3
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Worldwide total number of subjects |
11
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EEA total number of subjects |
8
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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) |
8
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Adolescents (12-17 years) |
3
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
11 subjects were recruited: 7 from the UK (3 sites), 1 from Spain, and 3 from Turkey (1 site). The first subject was randomised on 09/03/2015, and the last on 06/06/2018. 8 participating sites did not recruit. | |||||||||||||||
Pre-assignment
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Screening details |
13 subjects were screened. 1 did not meet eligibility criteria, and 1 did not agree to participate. | |||||||||||||||
Period 1
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Period 1 title |
Baseline
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Mycophenolate mofetil (MMF) | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Mycophenolate mofetil
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Investigational medicinal product code |
24280-93-1
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Other name |
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Pharmaceutical forms |
Powder and solvent for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
For ease of administration, for the tablets and capsules the dose should be rounded to the nearest multiple of 250 (as long as within 10% of target dose).
The 1g/5ml powder should be reconstituted in accordance with the manufacturer’s SmPC.
The starting dose is 600 mg/m² per day (maximum 1g per day) for the first week. Thereafter the dose is 1200 mg/m² per day, maximum 2g per day, in two divided doses.
MMF may be stopped from 3 months onward provided patient in remission (PVAS 0 for 2 consecutive study assessments at least 1 month apart). After completion of MMF, AZA to be commenced the next day.
If the target dose is not tolerated, patients should receive the maximum tolerated dose.
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Arm title
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Intravenous Cyclophosphamide (CYC) | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
Cyclophosphamide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
The preparation of CYC should be in accordance with the manufacturer’s instructions on intravenous infusion, provided on the relevant SmPC.
MESNA and IV fluids will be administered as per existing local practice.
- CYC is given as intravenous pulses at weeks 0, 2, 4 and then every 3 weeks until remission is reached from start of therapy (max 10 doses, min 6 doses) at a dose of 500-750 mg/m2 (maximum 1.2g).
- The dose is adjusted based on Leukocyte count, hepatic, and renal function according to a standard protocol (see Table 1).
- CYC may be stopped after a minimum of 6 doses (week 13) provided patient in remission (PVAS 0 for 2 consecutive study assessments at least a month (4 weeks) apart and adhering to protocol steroid taper).
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Period 2
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Period 2 title |
Treatment
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Mycophenolate mofetil (MMF) | |||||||||||||||
Arm description |
3-6 months (12-24 weeks) induction therapy with oral MMF | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Mycophenolate mofetil
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Investigational medicinal product code |
24280-93-1
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Other name |
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Pharmaceutical forms |
Powder and solvent for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
For ease of administration, for the tablets and capsules the dose should be rounded to the nearest multiple of 250 (as long as within 10% of target dose).
The 1g/5ml powder should be reconstituted in accordance with the manufacturer’s SmPC.
The starting dose is 600 mg/m² per day (maximum 1g per day) for the first week. Thereafter the dose is 1200 mg/m² per day, maximum 2g per day, in two divided doses.
MMF may be stopped from 3 months onward provided patient in remission (PVAS 0 for 2 consecutive study assessments at least 1 month apart). After completion of MMF, AZA to be commenced the next day.
If the target dose is not tolerated, patients should receive the maximum tolerated dose.
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Investigational medicinal product name |
Prednisolone
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Investigational medicinal product code |
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Other name |
Prednisone / Methylprednisolone
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Both groups will receive the same protocolised prednisolone/prednisone starting at 1mg/kg/day weaning to 0.1 mg/kg/day by 6 months (24 weeks)
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Arm title
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Intravenous Cyclophosphamide (CYC) | |||||||||||||||
Arm description |
3-6 months (12-24 weeks) induction therapy with intravenous CYC regimen | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
Cyclophosphamide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
The preparation of CYC should be in accordance with the manufacturer’s instructions on intravenous infusion, provided on the relevant SmPC.
MESNA and IV fluids will be administered as per existing local practice.
- CYC is given as intravenous pulses at weeks 0, 2, 4 and then every 3 weeks until remission is reached from start of therapy (max 10 doses, min 6 doses) at a dose of 500-750 mg/m2 (maximum 1.2g).
- The dose is adjusted based on Leukocyte count, hepatic, and renal function according to a standard protocol (see Table 1).
- CYC may be stopped after a minimum of 6 doses (week 13) provided patient in remission (PVAS 0 for 2 consecutive study assessments at least a month (4 weeks) apart and adhering to protocol steroid taper).
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Investigational medicinal product name |
Prednisolone
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Investigational medicinal product code |
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Other name |
Prednisone / Methylprednisolone
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Both groups will receive the same protocolised prednisolone/prednisone starting at 1mg/kg/day weaning to 0.1 mg/kg/day by 6 months (24 weeks)
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Period 3
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Period 3 title |
Follow-up
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Mycophenolate mofetil (MMF) | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Azathioprine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Dose is 2 mg/kg/day, maximum 200 mg/day, rounded to the nearest 25 mg. Weight at time of commencing azathioprine to be used for dose calculation.
- Check FBC and alanine transaminase (ALT) or aspartate transaminase (AST) (for hepatotoxicity):
a. Every two weeks for one month (4 weeks)
b. Every two months (8 weeks) for the first 12 months (48 weeks)
c. Then three-monthly (every 12 weeks)
- Stop if leukocytes <4.0 x 109 cells/l. Restart when leukocytes ≥ 4.0 x109 cells/l with AZA dose reduced by at least 25%. Monitor weekly for one month (4 weeks).
- If liver transaminases are over twice upper limit of normal level then Azathioprine should be temporarily discontinued.
- Thiopurine s-methyltransferase (TPMT) activity or polymorphism assessment to be used according to local practice, but this is not a mandatory requirement.
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Investigational medicinal product name |
Prednisolone
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Investigational medicinal product code |
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Other name |
Prednisone / Methylprednisolone
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
0.05-0.075 mg/kg by 9 months (36 weeks) and until trial end at 18 months (72 weeks).
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Arm title
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Intravenous Cyclophosphamide (CYC) | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
Azathioprine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Dose is 2 mg/kg/day, maximum 200 mg/day, rounded to the nearest 25 mg. Weight at time of commencing azathioprine to be used for dose calculation.
- Check FBC and alanine transaminase (ALT) or aspartate transaminase (AST) (for hepatotoxicity):
a. Every two weeks for one month (4 weeks)
b. Every two months (8 weeks) for the first 12 months (48 weeks)
c. Then three-monthly (every 12 weeks)
- Stop if leukocytes <4.0 x 109 cells/l. Restart when leukocytes ≥ 4.0 x109 cells/l with AZA dose reduced by at least 25%. Monitor weekly for one month (4 weeks).
- If liver transaminases are over twice upper limit of normal level then Azathioprine should be temporarily discontinued.
- Thiopurine s-methyltransferase (TPMT) activity or polymorphism assessment to be used according to local practice, but this is not a mandatory requirement.
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Investigational medicinal product name |
Prednisolone
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Investigational medicinal product code |
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Other name |
Prednisone / Methylprednisolone
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
0.05-0.075 mg/kg by 9 months (36 weeks) and until trial end at 18 months (72 weeks).
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Baseline characteristics reporting groups
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Reporting group title |
Mycophenolate mofetil (MMF)
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Intravenous Cyclophosphamide (CYC)
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Mycophenolate mofetil (MMF)
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Reporting group description |
- | ||
Reporting group title |
Intravenous Cyclophosphamide (CYC)
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Reporting group description |
- | ||
Reporting group title |
Mycophenolate mofetil (MMF)
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Reporting group description |
3-6 months (12-24 weeks) induction therapy with oral MMF | ||
Reporting group title |
Intravenous Cyclophosphamide (CYC)
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Reporting group description |
3-6 months (12-24 weeks) induction therapy with intravenous CYC regimen | ||
Reporting group title |
Mycophenolate mofetil (MMF)
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Reporting group description |
- | ||
Reporting group title |
Intravenous Cyclophosphamide (CYC)
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Reporting group description |
- |
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End point title |
Remission within 24 weeks with adherence to protocolised corticosteroid taper | |||||||||
End point description |
Remission within six months (24 weeks) of randomisation defined as a paediatric vasculitis activity score (PVAS) of zero on two consecutive readings (both within 6 months (24 weeks) of randomisation ≥ one month (4 weeks) apart, with adherence to the protocolised corticosteroid taper.
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End point type |
Primary
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End point timeframe |
24 weeks
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Statistical analysis title |
Bayesian analysis | |||||||||
Statistical analysis description |
Calculation of a posterior distribution for the probability of remission within 6-months of randomisation to MMF
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Comparison groups |
Mycophenolate mofetil (MMF) v Intravenous Cyclophosphamide (CYC)
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Number of subjects included in analysis |
11
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | |||||||||
Method |
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Parameter type |
Probability | |||||||||
Point estimate |
0.71
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.47 | |||||||||
upper limit |
0.85 | |||||||||
Notes [1] - Presentation of summary statistics for the posterior distribution (mode and 95% credible interval) |
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Statistical analysis title |
Bayesian analysis | |||||||||
Statistical analysis description |
Calculation of a posterior distribution for the probability of remission within 6-months of randomisation to CYC
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Comparison groups |
Mycophenolate mofetil (MMF) v Intravenous Cyclophosphamide (CYC)
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Number of subjects included in analysis |
11
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Analysis specification |
Pre-specified
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Analysis type |
other [2] | |||||||||
Method |
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Parameter type |
Probability | |||||||||
Point estimate |
0.75
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.53 | |||||||||
upper limit |
0.87 | |||||||||
Notes [2] - Presentation of summary statistics for the posterior distribution (mode and 95% credible interval) |
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Statistical analysis title |
Bayesian analysis | |||||||||
Statistical analysis description |
Calculation of a posterior distribution for the odds-ratio of remission within 6-months of randomisation to MMF vs CYC
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Comparison groups |
Mycophenolate mofetil (MMF) v Intravenous Cyclophosphamide (CYC)
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Number of subjects included in analysis |
11
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Analysis specification |
Pre-specified
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Analysis type |
other [3] | |||||||||
Method |
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Parameter type |
Probability | |||||||||
Point estimate |
0.81
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.34 | |||||||||
upper limit |
1.88 | |||||||||
Notes [3] - Presentation of summary statistics for the posterior distribution (mode and 95% credible interval) |
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End point title |
Remission within 24 weeks irrespective of adherence to protocolised corticosteroid taper | |||||||||
End point description |
Remission within six months (24 weeks) of randomisation defined as paediatric vasculitis activity score (PVAS) of zero on two consecutive readings ≥ one month (4 weeks) apart, irrespective of adherence to a protocolised corticosteroid taper
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End point type |
Secondary
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End point timeframe |
24 weeks
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Statistical analysis title |
Fisher's exact test | |||||||||
Statistical analysis description |
Does treatment arm have a significant effect on remission rates
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Comparison groups |
Mycophenolate mofetil (MMF) v Intravenous Cyclophosphamide (CYC)
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Number of subjects included in analysis |
11
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 1 | |||||||||
Method |
Fisher exact | |||||||||
Parameter type |
Relative Risk | |||||||||
Point estimate |
1.2
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.6 | |||||||||
upper limit |
2.5 |
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End point title |
Time to remission, with adherence to a protocolised corticosteroid taper | ||||||||||||
End point description |
Time to remission defined as PVAS of zero on two consecutive readings ≥ one month (4 weeks) apart, with adherence to a protocolised corticosteroid taper, measured from randomisation
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End point type |
Secondary
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End point timeframe |
From randomisation to 72 weeks
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Attachments |
Kaplan-Meier curve showing time to remission |
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No statistical analyses for this end point |
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End point title |
Paediatric vasculitis damage index (PVDI) at 24 weeks | ||||||||||||
End point description |
Paediatric vasculitis damage index (PVDI – modified from the adult VDI) at 6, 12 and 18 months (24, 48 and 72 weeks) after randomisation
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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 |
Paediatric vasculitis damage index (PVDI) at 48 weeks | ||||||||||||
End point description |
Paediatric vasculitis damage index (PVDI – modified from the adult VDI) at 6, 12 and 18 months (24, 48 and 72 weeks) after randomisation
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End point type |
Secondary
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End point timeframe |
48 weeks
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No statistical analyses for this end point |
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End point title |
Paediatric vasculitis damage index (PVDI) at 72 weeks | ||||||||||||
End point description |
Paediatric vasculitis damage index (PVDI – modified from the adult VDI) at 6, 12 and 18 months (24, 48 and 72 weeks) after randomisation
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End point type |
Secondary
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End point timeframe |
72 weeks
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Attachments |
MMF PVDI over time CYC PVDI over time |
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No statistical analyses for this end point |
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End point title |
CHAQ Disability Index at Baseline | ||||||||||||
End point description |
The Childhood Health Assessment Questionnaire (CHAQ) is a functional outcome score measuring disability, pain, and general health.
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End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHAQ Disability Index at 16 weeks | ||||||||||||
End point description |
The Childhood Health Assessment Questionnaire (CHAQ) is a functional outcome score measuring disability, pain, and general health.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
16 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHAQ Disability Index at 24 weeks | ||||||||||||
End point description |
The Childhood Health Assessment Questionnaire (CHAQ) is a functional outcome score measuring disability, pain, and general health.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
24 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHAQ Disability Index at 48 weeks | ||||||||||||
End point description |
The Childhood Health Assessment Questionnaire (CHAQ) is a functional outcome score measuring disability, pain, and general health.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
48 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHAQ Disability Index at 72 weeks | ||||||||||||
End point description |
The Childhood Health Assessment Questionnaire (CHAQ) is a functional outcome score measuring disability, pain, and general health.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
72 weeks
|
||||||||||||
|
|||||||||||||
Attachments |
MMF CHAQ disability Patient Profiles CYC CHAQ Disability: Patient Profiles |
||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHAQ Pain at Baseline | ||||||||||||
End point description |
The Childhood Health Assessment Questionnaire (CHAQ) is a functional outcome score measuring disability, pain, and general health.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHAQ Pain at 16 weeks | ||||||||||||
End point description |
The Childhood Health Assessment Questionnaire (CHAQ) is a functional outcome score measuring disability, pain, and general health.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
16 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHAQ Pain at 24 weeks | ||||||||||||
End point description |
The Childhood Health Assessment Questionnaire (CHAQ) is a functional outcome score measuring disability, pain, and general health.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
24 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHAQ Pain at 48 weeks | ||||||||||||
End point description |
The Childhood Health Assessment Questionnaire (CHAQ) is a functional outcome score measuring disability, pain, and general health.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
48 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHAQ Pain at 72 weeks | ||||||||||||
End point description |
The Childhood Health Assessment Questionnaire (CHAQ) is a functional outcome score measuring disability, pain, and general health.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
72 weeks
|
||||||||||||
|
|||||||||||||
Attachments |
MMF CHAQ Pain: Patient Profiles CYC CHAQ Pain: Patient Profiles |
||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHAQ General Evaluation at Baseline | ||||||||||||
End point description |
The Childhood Health Assessment Questionnaire (CHAQ) is a functional outcome score measuring disability, pain, and general evaluation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHAQ General Evaluation at 16 weeks | ||||||||||||
End point description |
The Childhood Health Assessment Questionnaire (CHAQ) is a functional outcome score measuring disability, pain, and general evaluation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
16 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHAQ General Evaluation at 24 weeks | ||||||||||||
End point description |
The Childhood Health Assessment Questionnaire (CHAQ) is a functional outcome score measuring disability, pain, and general evaluation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
24 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHAQ General Evaluation at 48 weeks | ||||||||||||
End point description |
The Childhood Health Assessment Questionnaire (CHAQ) is a functional outcome score measuring disability, pain, and general evaluation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
48 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHAQ General Evaluation at 72 weeks | ||||||||||||
End point description |
The Childhood Health Assessment Questionnaire (CHAQ) is a functional outcome score measuring disability, pain, and general evaluation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
72 weeks
|
||||||||||||
|
|||||||||||||
Attachments |
MMF CHAQ General Evaluation: Patient Profiles CYC CHAQ General Evaluation: Patient Profiles |
||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHQ Physical Summary Score (PhS) at Baseline | ||||||||||||
End point description |
The Child Health Questionnaire™ (CHQ) is a family of generic person-reported outcomes measures to assess health-related quality of life for children and adolescents from 5-to-18 years of age. Two sub-scores are derived: Physical Summary Score (PhS); and Psychosocial Summary Score (PsS)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHQ Physical Summary Score (PhS) at 16 weeks | ||||||||||||
End point description |
The Child Health Questionnaire™ (CHQ) is a family of generic person-reported outcomes measures to assess health-related quality of life for children and adolescents from 5-to-18 years of age. Two sub-scores are derived: Physical Summary Score (PhS); and Psychosocial Summary Score (PsS)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
16 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHQ Physical Summary Score (PhS) at 24 weeks | ||||||||||||
End point description |
The Child Health Questionnaire™ (CHQ) is a family of generic person-reported outcomes measures to assess health-related quality of life for children and adolescents from 5-to-18 years of age. Two sub-scores are derived: Physical Summary Score (PhS); and Psychosocial Summary Score (PsS)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
24 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHQ Physical Summary Score (PhS) at 48 weeks | ||||||||||||
End point description |
The Child Health Questionnaire™ (CHQ) is a family of generic person-reported outcomes measures to assess health-related quality of life for children and adolescents from 5-to-18 years of age. Two sub-scores are derived: Physical Summary Score (PhS); and Psychosocial Summary Score (PsS)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
48 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHQ Physical Summary Score (PhS) at 72 weeks | ||||||||||||
End point description |
The Child Health Questionnaire™ (CHQ) is a family of generic person-reported outcomes measures to assess health-related quality of life for children and adolescents from 5-to-18 years of age. Two sub-scores are derived: Physical Summary Score (PhS); and Psychosocial Summary Score (PsS)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
72 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHQ Psychosocial Summary Score (PsS) at Baseline | ||||||||||||
End point description |
The Child Health Questionnaire™ (CHQ) is a family of generic person-reported outcomes measures to assess health-related quality of life for children and adolescents from 5-to-18 years of age. Two sub-scores are derived: Physical Summary Score (PhS); and Psychosocial Summary Score (PsS)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHQ Psychosocial Summary Score (PsS) at 16 weeks | ||||||||||||
End point description |
The Child Health Questionnaire™ (CHQ) is a family of generic person-reported outcomes measures to assess health-related quality of life for children and adolescents from 5-to-18 years of age. Two sub-scores are derived: Physical Summary Score (PhS); and Psychosocial Summary Score (PsS)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
16 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHQ Psychosocial Summary Score (PsS) at 24 weeks | ||||||||||||
End point description |
The Child Health Questionnaire™ (CHQ) is a family of generic person-reported outcomes measures to assess health-related quality of life for children and adolescents from 5-to-18 years of age. Two sub-scores are derived: Physical Summary Score (PhS); and Psychosocial Summary Score (PsS)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
24 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHQ Psychosocial Summary Score (PsS) at 48 weeks | ||||||||||||
End point description |
The Child Health Questionnaire™ (CHQ) is a family of generic person-reported outcomes measures to assess health-related quality of life for children and adolescents from 5-to-18 years of age. Two sub-scores are derived: Physical Summary Score (PhS); and Psychosocial Summary Score (PsS)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
48 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
CHQ Psychosocial Summary Score (PsS) at 72 weeks | ||||||||||||
End point description |
The Child Health Questionnaire™ (CHQ) is a family of generic person-reported outcomes measures to assess health-related quality of life for children and adolescents from 5-to-18 years of age. Two sub-scores are derived: Physical Summary Score (PhS); and Psychosocial Summary Score (PsS)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
72 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Cumulative Oral Corticosteroid dose at 24 weeks | ||||||||||||
End point description |
Total oral corticosteroid prescribed from randomisation to 24 weeks
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
24 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Cumulative Oral Corticosteroid dose at 72 weeks | ||||||||||||
End point description |
Total oral corticosteroid prescribed from randomisation to 72 weeks
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
72 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Height z-score at 72 weeks | ||||||||||||
End point description |
Age and sex adjusted z-scores for height. A score of 0 means average height for that age/sex. Scores below -2 and above 2 indicate very unusual heights for age/sex.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
72 weeks
|
||||||||||||
|
|||||||||||||
Attachments |
MMF Height Z-scores: Profile plots CYC Height Z-scores: Profile plots |
||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Weight z-score at 72 weeks | ||||||||||||
End point description |
Age and sex adjusted z-scores for weight. A score of 0 means average weight for that age/sex. Scores below -2 and above 2 indicate very unusual weights for age/sex.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
72 weeks
|
||||||||||||
|
|||||||||||||
Attachments |
MMF Weight Z-scores: Profile plots CYC Weight Z-scores: Profile plots |
||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
BMI z-score at 72 weeks | ||||||||||||
End point description |
Age and sex adjusted z-scores for BMIt. A score of 0 means average BMI for that age/sex. Scores below -2 and above 2 indicate very unusual BMI for age/sex.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
72 weeks
|
||||||||||||
|
|||||||||||||
Attachments |
MMF BMI Z-scores: Profile plots CYC BMI Z-scores: Profile plots |
||||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Relapse rate | |||||||||
End point description |
A relapse is defined as a PVAS score > 0 occurring after remission.
In addition to the remission rate, it was also planned to report time-to-relapse, and rates of major/minor relapses. However, as no relapses were observed, we simply report the relapse rate.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
From point of remission to 72 weeks
|
|||||||||
|
||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
At least one adverse event, which may including drug toxicity | |||||||||
End point description |
||||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
From randomisation to 72 weeks
|
|||||||||
|
||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Time from randomisation to death | |||||||||
End point description |
The endpoint was planned as a time-to-event. However, as no subjects died, we report this as a rate.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
From randomisation to 72 weeks
|
|||||||||
|
||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Quality-adjusted life years (QALYs) | ||||||||||||
End point description |
Measure of utility of treatments
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation to 18 months
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Mycophenolate mofetil (MMF) v Intravenous Cyclophosphamide (CYC)
|
||||||||||||
Number of subjects included in analysis |
11
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.047
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.575 | ||||||||||||
upper limit |
0.48 |
|
|||||||||||||
End point title |
Probability of cost-effectiveness at £20,000 per QALY threshold | ||||||||||||
End point description |
Cost-effectiveness acceptability
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation to 18 months
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Probability of cost-effectiveness at £30,000 per QALY threshold | ||||||||||||
End point description |
Probability of cost-effectiveness at £30,000 per QALY threshold
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation to 18 months
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Disaggregated 18-month costs: Day-case admittance | ||||||||||||
End point description |
Total costs associated with admission to hospital where an overnight stay was not required
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation to 18 months
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Mycophenolate mofetil (MMF) v Intravenous Cyclophosphamide (CYC)
|
||||||||||||
Number of subjects included in analysis |
11
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
3208
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1786 | ||||||||||||
upper limit |
12112 |
|
|||||||||||||
End point title |
Disaggregated 18-month costs: Out-patient clinic | ||||||||||||
End point description |
Costs associated with out-patient clinic attendance
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation to 18 months
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Mycophenolate mofetil (MMF) v Intravenous Cyclophosphamide (CYC)
|
||||||||||||
Number of subjects included in analysis |
11
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-962
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1835 | ||||||||||||
upper limit |
-83 |
|
|||||||||||||
End point title |
Disagreggated 18 month costs: General ward visit | ||||||||||||
End point description |
Cost arising from general ward visits
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation to 18 months
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Mycophenolate mofetil (MMF) v Intravenous Cyclophosphamide (CYC)
|
||||||||||||
Number of subjects included in analysis |
11
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
68
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-486 | ||||||||||||
upper limit |
623 |
|
|||||||||||||
End point title |
Disagreggated 18 month costs: Concomitant medications | ||||||||||||
End point description |
Costs arising from concomitant medications
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation to 18 months
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Mycophenolate mofetil (MMF) v Intravenous Cyclophosphamide (CYC)
|
||||||||||||
Number of subjects included in analysis |
11
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-401
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1670 | ||||||||||||
upper limit |
255 |
|
|||||||||||||
End point title |
Disagreggated 18 month costs: Azathioprine | ||||||||||||
End point description |
Costs associated with the medication Azathioprine
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation to 18 months
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Mycophenolate mofetil (MMF) v Intravenous Cyclophosphamide (CYC)
|
||||||||||||
Number of subjects included in analysis |
11
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-1512
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-6015 | ||||||||||||
upper limit |
3 |
|
|||||||||
End point title |
Disagreggated 18 month costs: Cyclophosphamide | ||||||||
End point description |
Costs associated with the treatment Cyclophosphamide (CYC treatment arm only)
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Randomisation to 18 months
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Disagreggated 18 month costs: Mycophenolate mofetil | ||||||||
End point description |
Costs associated with the treatment Mycophenolate mofetil (MMF treatment arm only)
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Randomisation to 18 months
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Disagreggated 18 month costs: Corticosteroids | ||||||||||||
End point description |
Costs associated with corticosteroids
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation to 18 months
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Mycophenolate mofetil (MMF) v Intravenous Cyclophosphamide (CYC)
|
||||||||||||
Number of subjects included in analysis |
11
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-18 | ||||||||||||
upper limit |
12 |
|
|||||||||||||
End point title |
Mean total discounted costs | ||||||||||||
End point description |
Total costs associated with each treatment group
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation to 18 months
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Mean difference | ||||||||||||
Comparison groups |
Mycophenolate mofetil (MMF) v Intravenous Cyclophosphamide (CYC)
|
||||||||||||
Number of subjects included in analysis |
11
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
1346
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-4709 | ||||||||||||
upper limit |
11175 |
|
|||||||||||||
End point title |
Incremental net health benefit (INHB): Cost effectiveness threshold £20,000 per QALY | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation to 18 months
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Incremental analysis | ||||||||||||
Comparison groups |
Mycophenolate mofetil (MMF) v Intravenous Cyclophosphamide (CYC)
|
||||||||||||
Number of subjects included in analysis |
11
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [4] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.114
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.8 | ||||||||||||
upper limit |
0.574 | ||||||||||||
Notes [4] - Incremental analysis |
|
|||||||||||||
End point title |
Incremental net health benefit (INHB): Cost effectiveness threshold £30,000 per QALY | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Randomisation to 18 months
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Incremental analysis | ||||||||||||
Comparison groups |
Mycophenolate mofetil (MMF) v Intravenous Cyclophosphamide (CYC)
|
||||||||||||
Number of subjects included in analysis |
11
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [5] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.092
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.695 | ||||||||||||
upper limit |
0.5 | ||||||||||||
Notes [5] - Incremental analysis |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Randomisation to 72 weeks
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Mycophenolate mofetil (MMF)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Intravenous Cyclophosphamide (CYC)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
29 Sep 2014 |
Changes to Protocol. Documents submitted: Protocol V2.0.
Protocol section 10.2.3 amended so that the reference to 48 weeks as been deleted as advised.
Protocol section 5.2, exclusion criteria revised to state that sexually active females are excluded if they are not prepared to use two reliable means of contraception for the complete duration of the trial and for 12 months after study drug therapy is discontinued.
Protocol section 7.10.1 amended to state that “For patients of reproductive potential (males and females), use of reliable means of contraception as stated in Exclusion Criteria is required throughout study participation and for 12 months after study drug therapy is discontinued.” Abstinence is acceptable in the trial and section 5.2, exclusion criteria 15 has been amended to show abstinence is acceptable only if it is the preferred and usual lifestyle of the patient.
Protocol section 7.3.2 has been updated to state that protection from UV-light exposure is mandatory and patients should wear sunscreen SPF 50+ when exposed to UV-light. Protocol section 2.4 has also been updated to add UV-light exposure as a potential trial risk.
Protocol section 7.10.2 has been updated to state that live vaccinations are not permitted for the duration of the trial period.
The protocol has been updated following the telephone conversation with Farhat Gilani Pharmacovigilance Manager, University College London, to show that SAE’s which are not related to disease progression will be reported within 24 hours of becoming aware of the event. SAE’s that are symptoms due to disease progression will be reported on the adverse event forms which are submitted within fourteen days of the patient visit.
A MYPAN website will be created at the address www.mypantrial.org.uk. The website will display information about the trial, including a summary, location of the sites involved, links to collaborators, methods of contacting the trial team and updates on recruitment figures.
|
||
26 Oct 2015 |
Addition of UK site – Addenbrookes Hospital
Removal of UK Site – Queens Medical Centre, Nottingham
|
||
17 Dec 2015 |
Changes to Protocol. Documents submitted: Protocol V3.0, Amendment assessment form, Notification of substantial amendment, Cover letter, SmPC Cellcept oral suspension, SmPC Cellcept 250mg,
SmPC Cellcept 500mg |
||
29 Feb 2016 |
Addition of two UK sites: University College London University Hospital and Royal Free Hospital
Removal of UK Site – Bristol University Hospital
|
||
04 May 2016 |
Substantial changes have been made to the contraceptive advice in the SmPC for Mycophenolate Mofetil. This advice is now reflected in the updated PISCs for the adults and parents. |
||
26 Oct 2016 |
The IRAS form has been updated to declare the use of X-Rays as a screening tool to rule out infections prior to commencement in the study.
The patient information sheets and consent forms have been updated to give participants more information about the use of X-Rays as part of the study and the risks involved. |
||
17 Jul 2017 |
Documents submitted: Protocol V4.0.
Recruitment period extended from 30th January 2018 to 0th June 2018
Section 5.1: Inclusion criteria. Text updated to clarify that if the patient was not adequately treated at the time of diagnosis then they may still be eligible for the study.
Section 9: Removal of interim monitoring and analysis
Section 10.9.2: Clarification of urgent safety measures reporting procedures |
||
24 May 2018 |
GDPR information letter sent out to patient and parents, including information correctly notifying them about the way their consent forms have been handled.
Section 4.4. and 4.8 amended with new RSI information |
||
28 Nov 2019 |
Update to the Reference Safety Information (section 4.4 and 4.8) for the trial after an update to the SmPC for Cellcept.
|
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |