Clinical Trial Results:
Open label study of the efficacy and safety of isavuconazole for the treatment of Chronic Pulmonary Aspergillosis
Summary
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EudraCT number |
2016-003921-40 |
Trial protocol |
GB |
Global end of trial date |
22 May 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
09 Feb 2020
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First version publication date |
09 Feb 2020
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Other versions |
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Summary report(s) |
2016IF002 statement |
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 |
2016IF002
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
REC reference: 17/NW/0298 | ||
Sponsors
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Sponsor organisation name |
Manchester University NHS Foundation Trust
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Sponsor organisation address |
29 Grafton Street, Manchester, United Kingdom, M13 9WU
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Public contact |
Dr Lynne Webster, Manchester University NHS Foundation Trust, +44 161276 4125, research.sponsor@mft.nhs.uk
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Scientific contact |
Dr Lynne Webster, Manchester University NHS Foundation Trust, +44 161276 4125, research.sponsor@mft.nhs.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 |
22 May 2015
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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 |
22 May 2015
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
Isavuconazole is an antifungal agent that was recently approved for the treatment of invasive aspergillosis on the basis of non-inferior outcomes compared to the standard of care, voriconazole. Isavuconazole is associated with a lower incidence of side effects than current standard treatment with antifungal drugs. There are no data on the use of isavuconazole in chronic pulmonary aspergillosis (CPA). The trial hypothesis is that isavuconazole will be at least as effective and safe as current available therapy for CPA.
The primary objective of the study is to assess the efficacy and safety of isavuconazole in the treatment of CPA.
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Protection of trial subjects |
The most common treatment-related adverse reactions are elevated liver chemistry (7.9%). These changes are not related to liver failure and rarely requires stopping of treatment. Monitoring of liver enzymes during treatment will be considered during study scheduled visits. Isavuconazole has a moderate effect on the ability of patients to drive and use machines. Patients will be advised to avoid driving or operating machinery if symptoms of confusional state, somnolence, fainting and/or dizziness are experienced. Patients on treatment will be seen in the clinic at regular intervals to check for the signs and symptoms of adverse reactions. Patients will be provided with supportive care to reduce the burden of the side effects. Female patients of childbearing age are advised to use effective methods of contraception to prevent pregnancy. Patients are screened for pregnancy at regular intervals during the scheduled visits. In case of overdose, there is no specific treatment but patients will be treated with supportive care and appropriate medical support will be provided . As a preventative measure and to check compliance, the patient diary and number of capsules taken and returned will be checked during each visit to ensure overdose has not occured and also to check if the patient is receiving adequate level of treatment.
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Background therapy |
None. | ||
Evidence for comparator |
N/A | ||
Actual start date of recruitment |
01 Jan 1900
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 99999
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Worldwide total number of subjects |
99999
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EEA total number of subjects |
99999
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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) |
99999
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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 |
Potential participants will be identified through screening of the patients referred to the National Aspergillosis Centre by their local GP or consultant with suspected diagnosis of CPA. Potential participants who are deemed to be eligible or meeting the inclusion criteria will be provided with a participant information sheet. | ||||||
Pre-assignment
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Screening details |
Inclusion criteria: 1. Willing to give informed consent 2. Male or female aged 18 years plus 3. Diagnosed with CPA with azoles treatment indicated 4. Participants must not have received antifungals for treatment of CPA in the last 6 months and not for longer than 3 months 5. Sexually active females must agree to effective contraception | ||||||
Period 1
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Period 1 title |
Isavuconazole (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Blinding implementation details |
This was an open label study with no active comparator or placebo so no blinding was to take place.
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Arms
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Arm title
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Isavuconazole treatment | ||||||
Arm description |
Eligible patients will be treated with isavuconazole (200mg) three times daily for 6 doses, followed by 200mg once daily. Patients will attend scheduled visits at 1, 2, 4, 6, 9, , 12, 16, 20, 24, 30, 36, 44 and 52 weeks of treatment and followed up for 6 months with two scheduled visits at 12 and 24 week after the end of treatment. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Cresemba 100 mg hard capsules
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Eligible patients will be treated with isavuconazole (200mg) three times daily for 6 doses, followed by 200mg once daily. Patients will attend scheduled visits at 1, 2, 4, 6, 9, , 12, 16, 20, 24, 30, 36, 44 and 52 weeks of treatment and followed up for 6 months with two scheduled visits at 12 and 24 week after the end of treatment.
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End points reporting groups
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Reporting group title |
Isavuconazole treatment
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Reporting group description |
Eligible patients will be treated with isavuconazole (200mg) three times daily for 6 doses, followed by 200mg once daily. Patients will attend scheduled visits at 1, 2, 4, 6, 9, , 12, 16, 20, 24, 30, 36, 44 and 52 weeks of treatment and followed up for 6 months with two scheduled visits at 12 and 24 week after the end of treatment. |
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End point title |
Monitoring of clinical and biochemical evidence of toxicity throughout treatment period [1] | ||||||
End point description |
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End point type |
Primary
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End point timeframe |
Within treatment period
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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: This trial was terminated prior to opening at the trust. |
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No statistical analyses for this end point |
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End point title |
Clinical and radiological evidence of response to treatment after 12 months of therapy , as assessed by response on chest CT scan and clinical response (assessed using the SGRQ) and classified as improvement, stability and deterioration [2] | ||||||
End point description |
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End point type |
Primary
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End point timeframe |
After 12 months of treatment
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This trial was terminated prior to opening at the trust. |
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No statistical analyses for this end point |
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End point title |
Serological response (improvement in Aspergillus IgG by 20% or to <40mg/L after 6 and 12 months of treatment) | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
After 6 and 12 months of treatment
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No statistical analyses for this end point |
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End point title |
Discontinuation of study drug before 12 months | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Before 12 months
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No statistical analyses for this end point |
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End point title |
Symptomatic improvement (any 2 key symptoms other than weight gain) | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
After follow up complete
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No statistical analyses for this end point |
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End point title |
Proportion of patients showing improvement in SGRQ by >8 points at 6 and 12 months | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At 6 and 12 months
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No statistical analyses for this end point |
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End point title |
Proportion of patients showing deterioration SGRQ by >4 points at 6 and 12 months | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At 6 and 12 months
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No statistical analyses for this end point |
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End point title |
Weight gain or loss of >3Kg at 6 and 12 months | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At 6 and 12 months
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No statistical analyses for this end point |
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End point title |
Recurrence 6 months after therapy discontinuation, assessed by deterioration in SGRQ by ≥8 points. | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
After 6 months of treatment
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No statistical analyses for this end point |
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End point title |
Positive respiratory culture for Aspergillus fumigatus with emergence of isavuconazole resistance | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
After follow up end
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No statistical analyses for this end point |
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End point title |
PK analysis of Isavuconazole in patients on treatment | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
After follow up completion
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No statistical analyses for this end point |
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End point title |
Inflammatory markers during treatment; C Reactive Protein and Plasma Viscosity | ||||||
End point description |
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End point type |
Other pre-specified
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End point timeframe |
Exploratory endpoint. After follow up complete.
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
All SAEs that occur between day 1 of treatment and 30 days post the last trial treatment dose administration (or after this date if the site investigator considers the event to be related to the trial treatment) must be submitted to the Sponsor.
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Assessment type |
Non-systematic | ||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||
Dictionary version |
0
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Reporting groups
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Reporting group title |
Isavuconazole treatment
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Reporting group description |
Eligible patients will be treated with isavuconazole (200mg) three times daily for 6 doses, followed by 200mg once daily. | ||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||
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Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: This trial was terminated prior to opening at the trust. As such, no adverse events occurred. |
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
This trial was cancelled as the company supplying the Investigational Medicinal Product (IMP) was brought out by another company who did not want to continue with the trial concept. No R&D confirmation of capacity and capability was given or contract |