Clinical Trial Results:
A double-blind, placebo-controlled, interventional parallel group study to evaluate the antiviral effect of a single nasal application of LTX-109 3% gel, in comparison to placebo gel, in subjects with COVID-19 infection
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Summary
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EudraCT number |
2021-000455-39 |
Trial protocol |
SE |
Global end of trial date |
22 Aug 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
28 May 2023
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First version publication date |
28 May 2023
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Other versions |
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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 |
C21-109-09
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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 |
Pharma Holdings AS
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Sponsor organisation address |
Killengreensgt. 2-8, postbox 1288, Tromsø, Norway, NO-9263
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Public contact |
Johnny Ryvoll, VP Business Development, Pharma Holdings AS, ryvoll@pharmaholdings.no
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Scientific contact |
Johnny Ryvoll, VP Business Development, Pharma Holdings AS, ryvoll@pharmaholdings.no
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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 Aug 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
22 Aug 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Aug 2022
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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 |
To evaluate the effect of a single dose of LTX-109 3% nasal gel on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load, as measured by a standardised reverse transcription quantitative polymerase chain reaction (RT-qPCR) method on the sample material after virus cultivation to quantify the amount of live virus in the samples, from the deep nasal cavity in subjects with COVID-19 infection, as compared to placebo.
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Protection of trial subjects |
The study was conducted in accordance with ethical principles that have their origin in the Declaration of Helsinki and are compliant with the International Conference of Harmonisation (ICH) Good Clinical Practice (GCP) E6 (R2) guidance, the European Union (EU) Clinical Trials Directive 2001/20/EC, and applicable local regulatory requirements.
It was the responsibility of the Investigator or an authorised associate to give each potential study subject adequate verbal and written information before any study specific assessments were performed. The information included the objectives and the procedures of the study as well as any risks or inconvenience involved. It was emphasised that participation in the study was voluntary and that the subject could withdraw from participation at any time and for any reason, without any prejudice. All subjects were given the opportunity to ask questions about the study and were given sufficient time to consider participation before signing the Informed consent form (ICF). For subjects who performed the SARS-CoV-2 antigen test (only applicable in Sweden) during screening, a separate brief written information about the test was provided and consent was given for the antigen test only. If the test is positive and the subject was assessed as eligible full written and verbal information about the study was provided and the ICF was signed by the subject and by the Investigator.
Documentation of the discussion and the date of informed consent were recorded in the source documentation and in the electronic case report form (eCRF). The subject information sheet and the signed ICF were filed by the Investigator for possible future audits and/or inspections.
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Background therapy |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
03 May 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 |
Sweden: 11
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Country: Number of subjects enrolled |
India: 22
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Worldwide total number of subjects |
33
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EEA total number of subjects |
11
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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) |
30
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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 |
Sweden: Recruitment via CTC’s database of volunteers & from advertising in media/social media. India: Recruitment through PI’s patient portfolios. The study was prematurely terminated due to recruitment challenges because of reduced spread of COVID-19 and high vaccination rates and coverage. Only 33 subjects (planned 60) were randomised. | |||||||||
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Pre-assignment
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Screening details |
A total of 34 subjects were screened and 33 were randomised and dosed in the study (11 in Sweden, 22 in India). 16 subjects were treated with a single dose of LTX-109 and 17 subjects received a single dose of placebo. All 33 dosed subjects completed all 3 study visits. | |||||||||
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Period 1
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Period 1 title |
Overall period
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | |||||||||
Blinding implementation details |
This was a double-blind study, and the allocation of treatments was not disclosed until clean file had been declared and the database had been locked. The LTX-109 and placebo were identical in appearance.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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LTX-109 3% w/w Gel | |||||||||
Arm description |
Subjects were randomised in a 1:1 ratio to receive 1 single dose of either active treatment (LTX-109 3% hydrogel; planned number: 30) or matching placebo (planned number: 30). This arm represents the active treatment group receiving LTX-109. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
LTX-109
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Gel
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Routes of administration |
Topical
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Dosage and administration details |
A single dose of LTX-109 3% gel was administered to the nasal passages on Day 1. Prior to application, the subjects were to blow their nose to try to remove as much mucus secretions as possible. The IMP was administered while the subject lied in a supine position. A large drop was applied in the anterior parts of the nose, in each nostril, so that it covered the anterior and posterior parts of the nasal cavity. It was important that the volume was large enough to cover the whole inner area of the nose. After application of the IMP to both nostrils, the nostrils were gently squeezed together and massaged. The subject had to remain in the supine position for 15 minutes after application. Subjects were not allowed to blow their nose within 30 min after application. The IMP could not be removed until 2 hours after application. Each tube of IMP was used for 1 single subject only.
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Arm title
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LTX-109 Placebo Gel | |||||||||
Arm description |
Subjects were randomised in a 1:1 ratio to receive 1 single dose of either active treatment (LTX-109 3% hydrogel; planned number: 30) or matching placebo (planned number: 30). This arm represents the group receiving placebo. | |||||||||
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 |
Gel
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Routes of administration |
Topical
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Dosage and administration details |
Placebo gel was identical in composition and appearance to the LTX-109 formulation but contained no drug substance. A single dose placebo gel was administered to the nasal passages on Day 1. Prior to application, the subjects were to blow their nose to try to remove as much mucus secretions as possible. The IMP was administered while the subject lied in a supine position. A large drop was applied in the anterior parts of the nose, in each nostril, so that it covered the anterior and posterior parts of the nasal cavity. It was important that the volume was large enough to cover the whole inner area of the nose. After application of the IMP to both nostrils, the nostrils were gently squeezed together and massaged. The subject had to remain in the supine position for 15 minutes after application. Subjects were not allowed to blow their nose within 30 min after application. The IMP could not be removed until 2 hours after application. Each tube of IMP was used for 1 single subject only.
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Baseline characteristics reporting groups
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Reporting group title |
LTX-109 3% w/w Gel
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Reporting group description |
Subjects were randomised in a 1:1 ratio to receive 1 single dose of either active treatment (LTX-109 3% hydrogel; planned number: 30) or matching placebo (planned number: 30). This arm represents the active treatment group receiving LTX-109. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
LTX-109 Placebo Gel
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Reporting group description |
Subjects were randomised in a 1:1 ratio to receive 1 single dose of either active treatment (LTX-109 3% hydrogel; planned number: 30) or matching placebo (planned number: 30). This arm represents the group receiving placebo. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
LTX-109 3% w/w Gel
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Reporting group description |
Subjects were randomised in a 1:1 ratio to receive 1 single dose of either active treatment (LTX-109 3% hydrogel; planned number: 30) or matching placebo (planned number: 30). This arm represents the active treatment group receiving LTX-109. | ||
Reporting group title |
LTX-109 Placebo Gel
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Reporting group description |
Subjects were randomised in a 1:1 ratio to receive 1 single dose of either active treatment (LTX-109 3% hydrogel; planned number: 30) or matching placebo (planned number: 30). This arm represents the group receiving placebo. | ||
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End point title |
Reduction in SARS-CoV-2 viral load, based on the deep nasal swab sample, from baseline (pre-dose) to 2 hours post-dose, as measured by a standardised RT-qPCR method after virus cultivation (Full analysis set) | |||||||||||||||||||||
End point description |
Nasal swab sampling for analysis of SARS-CoV-2 viral load was performed by qualified personnel, blinded to the treatment allocation, in a standardised manner at the pre-specified timepoints. At each sampling timepoint, a swab sample was collected using a sterile swab; 1 standard deep nose swab (one nostril). The swab was placed back into the sterile container and stored frozen (-80°C) until shipment. Analysis was performed by Viroclinics, Rotterdam, the Netherlands by a standardised RT-qPCR method on the sample material after virus cultivation. Details on the nasal swab sampling procedure, sample shipment and analyses were specified in separate manuals.
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End point type |
Primary
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End point timeframe |
Nasal swab sampling was performed Pre-dose (baseline) and 2 hours post-dose.
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Statistical analysis title |
Differences between active and placebo | |||||||||||||||||||||
Statistical analysis description |
The aim of the primary analysis was to show that the proportion of subjects with reduced viral load in the deep nasal cavity from baseline (pre-dose) to 2 hours post-dose was higher in the active treatment group than in the placebo group. A subject was classified as a success if the reduction in viral load was greater than 75%, otherwise the subject was classified as a failure. The primary endpoint was analysed using a Fisher’s exact test without without continuity correction.
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Comparison groups |
LTX-109 3% w/w Gel v LTX-109 Placebo Gel
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Number of subjects included in analysis |
23
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.0894 [1] | |||||||||||||||||||||
Method |
Fisher exact | |||||||||||||||||||||
Confidence interval |
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| Notes [1] - Fisher's exact test two-sided p-value. p-value <0.05 shows a significant difference between the groups. |
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End point title |
Reduction in SARS-CoV-2 viral load, based on the deep nasal swab sample, from baseline (pre-dose) to 2 hours post-dose, as measured by a standardised RT-qPCR method after virus cultivation (Full analysis set) - Relative change from baseline [2] | ||||||||||||
End point description |
Nasal swab sampling for analysis of SARS-CoV-2 viral load was performed by qualified personnel, blinded to the treatment allocation, in a standardised manner at the pre-specified timepoints. At each sampling timepoint, a swab sample was collected using a sterile swab; 1 standard deep nose swab (one nostril). The swab was placed back into the sterile container and stored frozen (-80°C) until shipment. Analysis was performed by Viroclinics, Rotterdam, the Netherlands by a standardised RT-qPCR method on the sample material after virus cultivation. Details on the nasal swab sampling procedure, sample shipment and analyses were specified in separate manuals.
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End point type |
Primary
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End point timeframe |
Nasal swab sampling was performed Pre-dose (baseline) and 2 hours post-dose.
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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: See Primary: Reduction in SARS-CoV-2 viral load, based on the deep nasal swab sample, from baseline (pre-dose) to 2 hours post-dose, as measured by a standardised RTqPCR method after virus cultivation. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Reduction in SARS-CoV-2 viral load, based on the anterior nasal swab sample, from baseline (pre-dose) to 2 hours post-dose, as measured by a standardised RT-qPCR method after virus cultivation (Full analysis set) | |||||||||||||||||||||
End point description |
Nasal swab sampling for analysis of SARS-CoV-2 viral load was performed by qualified personnel, blinded to the treatment allocation, in a standardised manner at the pre-specified timepoints. At each sampling timepoint, a swab sample was collected using a sterile swab; 1 standard deep nose swab (one nostril). The swab was placed back into the sterile container and stored frozen (-80°C) until shipment. Analysis was performed by Viroclinics, Rotterdam, the Netherlands by a standardised RT-qPCR method on the sample material after virus cultivation. Details on the nasal swab sampling procedure, sample shipment and analyses were specified in separate manuals.
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End point type |
Secondary
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End point timeframe |
Nasal swab sampling was performed Pre-dose (baseline) and 2 hours post-dose.
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Reduction in SARS-CoV-2 viral load, based on the anterior nasal swab sample, from baseline (pre-dose) to 2 hours post-dose, as measured by a standardised RT-qPCR method after virus cultivation (Full analysis set) - Relative change from baseline | ||||||||||||
End point description |
Nasal swab sampling for analysis of SARS-CoV-2 viral load was performed by qualified personnel, blinded to the treatment allocation, in a standardised manner at the pre-specified timepoints. At each sampling timepoint, a swab sample was collected using a sterile swab; 1 standard deep nose swab (one nostril). The swab was placed back into the sterile container and stored frozen (-80°C) until shipment. Analysis was performed by Viroclinics, Rotterdam, the Netherlands by a standardised RT-qPCR method on the sample material after virus cultivation. Details on the nasal swab sampling procedure, sample shipment and analyses were specified in separate manuals.
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End point type |
Secondary
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End point timeframe |
Nasal swab sampling was performed Pre-dose (baseline) and 2 hours post-dose.
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Frequency, intensity and seriousness of AEs (Safety analysis set) | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
Symptoms of COVID-19 not recorded at baseline, or worsening after IMP administration, were recorded as AEs. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 [12]. AEs were assessed as unlikely, possibly or probably related to the IMP.
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End point type |
Secondary
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End point timeframe |
AEs (including serious AEs [SAEs]) were collected from the start of IMP administration until the end-of-study visit of each part.
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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 |
AEs (including serious AEs [SAEs]) were collected from the start of IMP administration until the end-of-study visit of each part.
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Adverse event reporting additional description |
Symptoms of COVID-19 not recorded at baseline, or worsening after IMP administration, were recorded as AEs. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly or probably related to the IMP.
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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 |
23.1
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Reporting groups
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Reporting group title |
LTX-109 3% w/w Gel
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Reporting group description |
Subjects were randomised in a 1:1 ratio to receive 1 single dose of either active treatment (LTX-109 3% hydrogel; planned number: 30) or matching placebo (planned number: 30). This arm represents the active treatment group receiving LTX-109. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
LTX-109 Placebo Gel
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Reporting group description |
Subjects were randomised in a 1:1 ratio to receive 1 single dose of either active treatment (LTX-109 3% hydrogel; planned number: 30) or matching placebo (planned number: 30). This arm represents the group receiving placebo. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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07 May 2021 |
Revision of exclusion criteria No’s 2 and 5 to facilitate recruitment. |
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07 Jul 2021 |
Temporary halt in Sweden due stability issues with batch 7579/001. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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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. | |||||||
| Inter-individual variation was too large and sample size was too small to conclude if single dose of LTX-109 3% nasal gel administered to subjects with COVID-19 infection reduces the viral load in the deep nasal cavity and/or the anterior nose. | |||||||
