Clinical Trial Results:
A randomized, double-blind, placebo-controlled study to assess the safety and efficacy of ivermectin in asymptomatic and mild severity COVID-19 patients
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Summary
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EudraCT number |
2021-000166-15 |
Trial protocol |
HU |
Global end of trial date |
16 Jan 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Sep 2023
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First version publication date |
15 Sep 2023
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Other versions |
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Summary report(s) |
IVM Clinical Study Report Synopsis |
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 |
IVM-2021-01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
MEDITOP Pharmaceutical Ltd.
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Sponsor organisation address |
Ady Endre utca 1., Pilisborosjenő, Hungary, 2097
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Public contact |
Main information contact, MEDITOP Pharmaceutical Ltd., 36 26336400, info@meditop.hu
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Scientific contact |
Main information contact, MEDITOP Pharmaceutical Ltd., 36 26336400, info@meditop.hu
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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 |
05 Jun 2023
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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 |
16 Jan 2023
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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 |
Primary Objective: To assess the efficacy of per os ivermectin administration in asymptomatic and mild severity SARS-CoV-2 infected patients on reduction of virus load.
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Protection of trial subjects |
This clinical study was conducted in accordance with the principles laid down by the 18th World Medical Assembly (Helsinki, 1964) and all applicable amendments laid down by the World Medical Assemblies, and the Good Clinical Practice (ICH GCP E6 (R2)).
This clinical study was conducted in compliance with applicable international (EU) laws and regulations, and national laws and regulations of the country where the clinical study is performed, as well as any applicable guidelines.
Patients were informed of study related details in writing (Patient Information Leaflet – PIL) and via discussion with study investigator. Written informed consent Informed Consent Forms (ICFs) for participation in the study was obtained before performing any study-related procedures (including screening evaluations). PIL and ICFs for enrolled subjects and for subjects who are not subsequently enrolled were maintained at the study site.
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Background therapy |
• No standard of care COVID-19 therapies were allowed. For symptomatic relief of e.g. fever, sore throat, e.g. antipyretics, analgesics could be used concomitantly. • Concomitant or previous administration of any experimental, non-established COVID-19 therapy, either in off-label indication of a registered medicinal product or as a non-registered drug candidate in a clinical trial setting or compassionate use program (or equivalents thereof) was not allowed. | ||
Evidence for comparator |
NA Placebo comparator was used | ||
Actual start date of recruitment |
26 Mar 2021
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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 |
Hungary: 10
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Worldwide total number of subjects |
10
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EEA total number of subjects |
10
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
7
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
Ambulatory patients with confirmed SARS-CoV-2 infection by rapid antigen test OR polymerase chain reaction mild, and asymptomatic cases were enrolled in COVID treating hospital centers. Recruitment was later extended to general practitioners and COVID test sites. | |||||||||
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Pre-assignment
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Screening details |
Screening period could last up to 3 days (D-3 … D1). If appropriate (e.g. study entry could be warranted upon positive rapid SARS-CoV-2 antigen test), the screening visit could be considered also as Day 1, start of IMP (Investigation Medicinal Product) administration. In this case, activities applicable for both Screening and Day 1 were conducted o | |||||||||
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Pre-assignment period milestones
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Number of subjects started |
11 [1] | |||||||||
Number of subjects completed |
10 | |||||||||
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Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Screen failure: 1 | |||||||||
| Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 11 patients were screened and 10 enroled to the study. |
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Period 1
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Period 1 title |
Treatment
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | |||||||||
Blinding implementation details |
This was a double-blind study. Neither the patients, physicians nor managing CRO was aware of treatment arm. Blinding was achieved by placebo arm.
Breaking the blind - unmasking of treatment allocation was only to occur in a medical emergency, by the Investigator or its medical delegate (subinvestigator), preferably after consulting this action with the Sponsor. No code breaking was needed during the study.
Emergency code break envelopes were provided for the sites with each treatment Kit for
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | |||||||||
Arm description |
Placebo 5 x 3 mg tablets once daily | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo
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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 |
5 x 3 mg tablets once daily for 4 days
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Arm title
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Active | |||||||||
Arm description |
Ivermectin | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Ivermectin
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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 |
5 x 3 mg tablets once daily for 4 days
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Period 2
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Period 2 title |
Follow-up
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Is this the baseline period? |
No | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | |||||||||
Blinding implementation details |
Same as before
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | |||||||||
Arm description |
No treatment in this period | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo
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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 |
5 x 3 mg tablets once daily for 4 days
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Arm title
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Active | |||||||||
Arm description |
Ivermectin | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Ivermectin
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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 |
5 x 3 mg tablets once daily for 4 days
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Placebo 5 x 3 mg tablets once daily | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Active
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Reporting group description |
Ivermectin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Placebo 5 x 3 mg tablets once daily | ||
Reporting group title |
Active
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Reporting group description |
Ivermectin | ||
Reporting group title |
Placebo
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Reporting group description |
No treatment in this period | ||
Reporting group title |
Active
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Reporting group description |
Ivermectin | ||
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End point title |
Virus copy number [1] | ||||||||||||
End point description |
The percentage of virus copy number at Day7 compared to baseline (i.e. 100 * (the number of virus copies at Day 7 / number of virus copies at Screening).
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End point type |
Primary
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End point timeframe |
Screening to Day7
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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: Due to the high number of major PDs, especially on eligibility criteria, and critical PD about data quality and the low number of patients, patients were excluded from all efficacy analyses, only safety objectives were analysed. Efficacy endpoints that can be considered as safety endpoints were analysed within safety analysis. |
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| Notes [2] - Due to quality issues patients were excluded from all efficacy analyses [3] - Due to quality issues all patients were excluded from all efficacy analyses. |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Screening to D28 FU (EOS)
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Adverse event reporting additional description |
Adverse events, whether believed to be IMP-related or not, were recorded in the Case Report Forms. For all adverse events concomitant medications were noted.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Placebo 5 x 3 mg tablets once daily | |||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Active
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Reporting group description |
Ivermectin | |||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0.05% | ||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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06 Apr 2021 |
8.8.2. Protocol v3.0 06/Apr/2021
Approved on 10/May/2021
Summary of changes from version 2.2:
• Introduction of D28 phone visit to complete the post-COVID symptoms questionnaires with the patients
• New exclusion criteria: Start of COVID-19 related symptoms more than 5 days before start of treatment.
• New endpoints:
o Oxygen saturation as a secondary endpoint
o Post-COVID questionnaire as a secondary endpoint
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30 Mar 2022 |
8.8.3. Protocol v4.3 02/May/2022
Approved on 27/Apr/2022 (The approval text is for protocol v4.2 30/Mar/2022, but contains a condition that was implemented in version 4.3 of the protocol).
Summary of changes from version 3.0:
• Study population:
o Inclusion of patients at high risk for developing severe COVID-19 case can be enrolled if they are vaccinated three times and the last dose was given not more than 6 months before screening. (High risk patients were excluded from the study in previous versions)
o Deleted previous exclusion criteria that excluded current strong smoker patients as defined by smoking over 10 cigarettes a day, or its equivalent
o True abstinence included as an acceptable method for contraception (for both gender)
• Study interventions:
o Urine drug test and alcohol breath test were removed from screening procedure (had been mandatory at screening in previous versions)
o Day 18 visit was removed
o Physical examination and body weight no longer mandatory at Day 14
o Screening radiology examination (CT or X-ray) at the discretion of the investigator
• Definition of overdose was included in the clinical trial protocol
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Due to the high number of major PDs, especially on eligibility criteria, and critical PD about data quality and the low number of patients, patients were excluded from all efficacy analyses, only safety objectives were analysed. | |||
