E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Cumulative number of SARS-COV-2 infections as verified by PCR from routine nasal swabs performed every 28 days (symptomatic or asymptomatic) at week 12 after
initiation of therapy |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the capacity of azithromycin to prevent severe COVID-19 infections, defined as a combined endpoint of hospitalization and death in cancer patients undergoing active treatment with chemotherapy
- Severity of COVID-19 cases (see grading as defined by the WHO)
- All-cause mortality
- Safety and tolerability of IMP (clinical and laboratory, CTCAE criteria)
- Occurrence of viral or bacterial infections other than COVID-19
- Development of azithromycin-resistant bacterial strains as assessed by nasal swabs
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically confirmed cancer diagnosis
- Active disease in need of antineoplastic therapy
o treatment may include classical cytostatic agents, molecular targeted therapy, monoclonal antibodies bevacizumab, cetuximab, rituximab and
obinutuzumab (either alone or in combination with chemotherapy) and checkpoint inhibitors
o treatment may be ongoing or newly started
o oral, intravenous or subcutaneous application route is allowed
o adjuvant, neoadjuvant or palliative chemotherapy is allowed
o the planned treatment duration must be at least 3 months, i.e. 12 weeks
- Age ≥ 18 years
- Life expectancy of at least 3 months
- Adequate renal, cardiac and liver function to tolerate the treatment
- Normal QTc (≤ 450 ms) on ECG
- ECOG performance status of < 3
- Negative PCR for SARS-COV-2 not older than 28 days
- Capable of understanding the study and giving informed consent |
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E.4 | Principal exclusion criteria |
- Active COVID-19 as defined by clinical WHO criteria and a positive PCR for SARS-COV2
- Use of any investigational agent within 28 days prior to study start
- Ongoing radiotherapy
- A history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs
- Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction
abnormalities, and long QT syndrome (QTc interval >450ms).
- Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator
assessment)
- Inadequate kidney function: serum-creatinine >2.0 times upper normal limit
- Hepatic dysfunction: total bilirubin >1.5 times upper normal limit (unless due cancer involvement of liver or a known history of Gilbert's disease); ALT >2.5 times upper normal limit (unless due to disease involvement of liver); alkaline phosphatase >2.5 times upper normal
limit (unless due to disease involvement of the liver or bone marrow)
- Patients with active opportunistic infections
- Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at screening, pregnancy testing must be performed within 7 days of administration of IMP. Approved methods of
birth control must be used
- Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Adequate contraception is
defined as hormonal birth control, intrauterine device, double barrier method or total abstinence.
- Inability to swallow tablets/study medication |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of SARS-COV-2 infections (symptomatic or asymptomatic): detected by routine SARS-COV-2 tests in all patients treated at the Division of Oncology, Medical University of Vienna. During the SARSCOV-2 pandemic, the routine approach to patients undergoing
chemotherapy at our institution is PCR from nasal swabs taken every 28 days. The cumulative number of infections detected (symptomatic or asymptomatic) at week 8 after initiation of therapy in both treatment arms serves as the primary endpoint. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Number of patients experiencing severe COVID-19 infection defined as a combined endpoint of hospitalization or death at week 12 after initiation of therapy. COVID-19 cases are defined as outlined by the WHO, including a PCR for COVID-19 from any specimen (respiratory, blood,
urine, stool, other bodily fluids).
Severity of COVID-19 cases: The severity of cases will be classified as
suggested in the Blue Print for COVID-19 therapeutic trials by the WHO (range 0-8) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |