Trial Outcomes & Findings for Treatment of Adenoviral Conjunctivitis With SHP640 Compared to Placebo (NCT NCT02998554)
NCT ID: NCT02998554
Last Updated: 2021-06-09
Results Overview
Clinical resolution of adenoviral conjunctivitis was defined as the absence (score = 0) of bulbar conjunctival injection and watery conjunctival discharge in the study eye. Bulbar conjunctival injection was assessed based on a 0 (Normal conjunctival vascular pattern)-4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from the validated bulbar redness (VBR) scale. Watery conjunctival discharge was assessed based on a 0-3 scale (0 - None and 3 - Severe: Abundant quantity of watery discharge observed in the lower conjunctival fornix and in the lower lid margin). The study eye was defined based on participants bulbar conjunctival redness and watery conjunctival discharge scores, as well as his/her cell culture-immunofluorescence assay (CC-IFA) results at baseline. Higher scores represented worse symptoms for both scales. Percentage of participants with clinical resolution on Day 6 was reported.
TERMINATED
PHASE3
156 participants
Day 6
2021-06-09
Participant Flow
The study was conducted at 30 centers in the United States and Puerto Rico between 28 March 2017 (first participant first visit) and 16 May 2019 (last participant last visit).
A total of 156 participants were randomized and received the treatment. Out of them, 134 participants completed the study.
Participant milestones
| Measure |
SHP640
Participants administered one drop of SHP640 (Povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times daily (QID) for 7 days.
|
Placebo
Participants administered one drop of placebo ophthalmic solution in each eye QID for 7 days.
|
|---|---|---|
|
Overall Study
STARTED
|
79
|
77
|
|
Overall Study
COMPLETED
|
68
|
66
|
|
Overall Study
NOT COMPLETED
|
11
|
11
|
Reasons for withdrawal
| Measure |
SHP640
Participants administered one drop of SHP640 (Povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times daily (QID) for 7 days.
|
Placebo
Participants administered one drop of placebo ophthalmic solution in each eye QID for 7 days.
|
|---|---|---|
|
Overall Study
Adverse Event
|
8
|
3
|
|
Overall Study
Protocol deviation
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
2
|
6
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Lack of Efficacy
|
0
|
1
|
Baseline Characteristics
Treatment of Adenoviral Conjunctivitis With SHP640 Compared to Placebo
Baseline characteristics by cohort
| Measure |
SHP640
n=79 Participants
Participants administered one drop of SHP640 (Povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times daily (QID) for 7 days.
|
Placebo
n=77 Participants
Participants administered one drop of placebo ophthalmic solution in each eye QID for 7 days.
|
Total
n=156 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
42.4 Years
STANDARD_DEVIATION 21.57 • n=5 Participants
|
41.3 Years
STANDARD_DEVIATION 21.21 • n=7 Participants
|
41.9 Years
STANDARD_DEVIATION 21.33 • n=5 Participants
|
|
Sex: Female, Male
Female
|
47 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
100 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
32 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
10 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
68 Participants
n=5 Participants
|
58 Participants
n=7 Participants
|
126 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
10 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
64 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
132 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 6Population: Modified Intent to Treat (mITT) population consisted of a subset of the ITT Population who received at least one dose of investigational product and has a positive CC-IFA adenovirus test at baseline in the study eye. Here, the number of participants analyzed refer to the participants evaluable for this outcome.
Clinical resolution of adenoviral conjunctivitis was defined as the absence (score = 0) of bulbar conjunctival injection and watery conjunctival discharge in the study eye. Bulbar conjunctival injection was assessed based on a 0 (Normal conjunctival vascular pattern)-4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from the validated bulbar redness (VBR) scale. Watery conjunctival discharge was assessed based on a 0-3 scale (0 - None and 3 - Severe: Abundant quantity of watery discharge observed in the lower conjunctival fornix and in the lower lid margin). The study eye was defined based on participants bulbar conjunctival redness and watery conjunctival discharge scores, as well as his/her cell culture-immunofluorescence assay (CC-IFA) results at baseline. Higher scores represented worse symptoms for both scales. Percentage of participants with clinical resolution on Day 6 was reported.
Outcome measures
| Measure |
SHP640
n=9 Participants
Participants administered one drop of SHP640 (Povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times daily (QID) for 7 days.
|
Placebo
n=10 Participants
Participants administered one drop of placebo ophthalmic solution in each eye QID for 7 days.
|
|---|---|---|
|
Percentage of Participants With Clinical Resolution on Day 6
|
11.1 Percentage of participants
|
20.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Day 6Population: mITT population consisted of a subset of the ITT Population who received at least one dose of investigational product and has a positive CC-IFA adenovirus test at baseline in the study eye. Here, the number of participants analyzed refer to the participants evaluable for this outcome.
Adenoviral eradication for the study eye was defined as negative CC-IFA in that eye. The CC-IFA for each eye was conducted using conjunctival swab samples collected at each visit to determine the presence of adenovirus. The study eye was defined based on participant's bulbar conjunctival redness and watery conjunctival discharge scores, as well as his/her CC-IFA results at baseline. Percentage of participants with adenoviral eradication on Day 6 was reported.
Outcome measures
| Measure |
SHP640
n=9 Participants
Participants administered one drop of SHP640 (Povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times daily (QID) for 7 days.
|
Placebo
n=10 Participants
Participants administered one drop of placebo ophthalmic solution in each eye QID for 7 days.
|
|---|---|---|
|
Percentage of Participants With Adenoviral Eradication on Day 6
|
33.3 Percentage of participants
|
70.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Day 6 and 8Population: The study was terminated as the sponsor discontinued the SHP640 clinical development with reason unrelated to safety. Hence, for this outcome measure, the planned data collection and analysis was not performed.
Adenovirus viral titer was assessed by quantitative polymerase chain reaction (qPCR) in the study eye. The study eye was defined based on participant's bulbar conjunctival redness and watery conjunctival discharge scores, as well as his/her CC-IFA results at baseline.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 3, 8 and 12/ETPopulation: mITT population consisted of a subset of the ITT Population who received at least one dose of investigational product and has a positive CC-IFA adenovirus test at baseline in the study eye. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specific time point.
Adenoviral eradication for the study eye was defined as negative CC-IFA in that eye. CC-IFA for each eye was conducted using conjunctival swab samples collected at each visit to determine the presence of adenovirus. The study eye was defined based on participant's bulbar conjunctival redness and watery conjunctival discharge scores, as well as his/her CC-IFA results at baseline. Percentage of participants with adenoviral eradication on Day 3, 8 and 12/ET was reported.
Outcome measures
| Measure |
SHP640
n=9 Participants
Participants administered one drop of SHP640 (Povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times daily (QID) for 7 days.
|
Placebo
n=12 Participants
Participants administered one drop of placebo ophthalmic solution in each eye QID for 7 days.
|
|---|---|---|
|
Percentage of Participants With Adenoviral Eradication on Day 3, 8 and 12/Early Termination (ET)
Day 3
|
11.1 Percentage of participants
|
16.7 Percentage of participants
|
|
Percentage of Participants With Adenoviral Eradication on Day 3, 8 and 12/Early Termination (ET)
Day 8
|
71.4 Percentage of participants
|
66.7 Percentage of participants
|
|
Percentage of Participants With Adenoviral Eradication on Day 3, 8 and 12/Early Termination (ET)
Day 12/ET
|
77.8 Percentage of participants
|
100 Percentage of participants
|
SECONDARY outcome
Timeframe: Day 3, 8 and 12/ETPopulation: mITT population consisted of a subset of the ITT Population who received at least one dose of investigational product and has a positive CC-IFA adenovirus test at baseline in the study eye. Here, the number of participants analyzed refer to the participants evaluable for this outcome at specific time point.
Clinical resolution of adenoviral conjunctivitis was defined as the absence (score = 0) of bulbar conjunctival injection and watery conjunctival discharge in the study eye. Bulbar conjunctival injection was assessed based on a 0 (Normal conjunctival vascular pattern)-4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from the validated bulbar redness (VBR) scale. Watery conjunctival discharge was assessed based on a 0-3 scale (0 - None and 3 - Severe: Abundant quantity of watery discharge observed in the lower conjunctival fornix and in the lower lid margin). The study eye was defined based on participant's bulbar conjunctival redness and watery conjunctival discharge scores, as well as his/her cell culture-immunofluorescence assay (CC-IFA) results at baseline. Higher scores represented worse symptoms for both scales. Percentage of participants with clinical resolution on Day 3, 8 and 12/ET was reported.
Outcome measures
| Measure |
SHP640
n=9 Participants
Participants administered one drop of SHP640 (Povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times daily (QID) for 7 days.
|
Placebo
n=12 Participants
Participants administered one drop of placebo ophthalmic solution in each eye QID for 7 days.
|
|---|---|---|
|
Percentage of Participants With Clinical Resolution on Day 3, 8 and 12/Early Termination (ET)
Day 3
|
11.1 Percentage of participants
|
0 Percentage of participants
|
|
Percentage of Participants With Clinical Resolution on Day 3, 8 and 12/Early Termination (ET)
Day 8
|
14.3 Percentage of participants
|
44.4 Percentage of participants
|
|
Percentage of Participants With Clinical Resolution on Day 3, 8 and 12/Early Termination (ET)
Day 12/ET
|
33.3 Percentage of participants
|
50.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Day 3, 6, 8 and 12/ETPopulation: The study was terminated as the sponsor discontinued the SHP640 clinical development with reason unrelated to safety. Hence, for this outcome measure, the planned data collection and analysis was not performed.
Individual clinical signs scores for bulbar conjunctival injection and watery conjunctival discharge in the study eye were reported. Bulbar conjunctival injection was assessed based on a 0 (Normal conjunctival vascular pattern)-4 (Markedly prominent, intense diffuse hyperemia) scale which used pictures from the validated bulbar redness (VBR) scale. Watery conjunctival discharge was assessed based on a 0-3 scale (0 - None and 3 - Severe: Abundant quantity of watery discharge observed in the lower conjunctival fornix and in the lower lid margin). Higher score represented worse symptoms for both scores. The study eye was defined based on participant's bulbar conjunctival redness and watery conjunctival discharge scores, as well as his/her CC-IFA results at baseline.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 3, 6, 8 and 12/ETPopulation: The study was terminated as the sponsor discontinued the SHP640 clinical development with reason unrelated to safety. Hence, for this outcome measure, the planned data collection and analysis was not performed.
Global clinical score was the sum of bulbar conjunctival injection and watery conjunctival discharge in the study eye. Score range from 0 to 7 and higher scores represented worse symptoms. The study eye was defined based on participant's bulbar conjunctival redness and watery conjunctival discharge scores, as well as his/her CC-IFA results at baseline.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 3, 6, 8 and 12/ETPopulation: The study was terminated as the sponsor discontinued the SHP640 clinical development with reason unrelated to safety. Hence, for this outcome measure, the planned data collection and analysis was not performed.
Modified clinical resolution was defined as a global clinical score of 0 or 1 in the study eye. Global clinical score was the sum of bulbar conjunctival injection and watery conjunctival discharge. Score range from 0 to 7 and higher scores represent worse symptoms.The study eye was defined based on participant's bulbar conjunctival redness and watery conjunctival discharge scores, as well as his/her CC-IFA results at baseline.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 3, 6, 8 and 12/ETPopulation: The study was terminated as the sponsor discontinued the SHP640 clinical development with reason unrelated to safety. Hence, for this outcome measure, the planned data collection and analysis was not performed.
Expanded clinical resolution was defined as a global clinical score of 0, 1, or 2 with neither injection nor discharge having a score of 2 in the study eye. Global clinical score was the sum of bulbar conjunctival injection and watery conjunctival discharge. Score range from 0 to 7 and higher scores represent worse symptoms. The study eye was defined based on participant's bulbar conjunctival redness and watery conjunctival discharge scores, as well as his/her CC-IFA results at baseline.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 3, 6, 8 and 12/ETPopulation: The study was terminated as the sponsor discontinued the SHP640 clinical development with reason unrelated to safety. Hence, for this outcome measure, the planned data collection and analysis was not performed.
Cross-over infection to a participant's fellow eye for participants with only 1 infected eye at baseline was reported. The CC-IFA for each eye was conducted using conjunctival swab samples collected at each visit to determine the presence of adenovirus.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 3, 6, 8 and 12/ETPopulation: The study was terminated as the sponsor discontinued the SHP640 clinical development with reason unrelated to safety. Hence, for this outcome measure, the planned data collection and analysis was not performed.
Time to clinical resolution was reported based on the assessments in the study eye.The study eye was defined based on participant's bulbar conjunctival redness and watery conjunctival discharge scores, as well as his/her CC-IFA results at baseline.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From start of study drug administration up to Day 13Population: Safety Population consisted of all screened participants who received at least one dose of investigational product.
An adverse event (AE) was any unfavorable and unintended sign, symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE is considered related to the investigational drug product. Treatment-Emergent Adverse Events (TEAEs) were defined as those adverse events that occurred after the first dose of investigational product.
Outcome measures
| Measure |
SHP640
n=79 Participants
Participants administered one drop of SHP640 (Povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times daily (QID) for 7 days.
|
Placebo
n=77 Participants
Participants administered one drop of placebo ophthalmic solution in each eye QID for 7 days.
|
|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
|
28 Participants
|
17 Participants
|
Adverse Events
SHP640
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
SHP640
n=79 participants at risk
Participants administered one drop of SHP640 (Povidone-iodine \[PVP-I\] 0.6 percent \[%\] and Dexamethasone 0.1%) ophthalmic suspension in each eye 4 times daily (QID) for 7 days.
|
Placebo
n=77 participants at risk
Participants administered one drop of placebo ophthalmic solution in each eye QID for 7 days.
|
|---|---|---|
|
Eye disorders
Conjunctivitis allergic
|
2.5%
2/79 • Number of events 2 • From start of study drug administration up to Day 13
|
0.00%
0/77 • From start of study drug administration up to Day 13
|
|
Eye disorders
Corneal infiltrates
|
2.5%
2/79 • Number of events 2 • From start of study drug administration up to Day 13
|
2.6%
2/77 • Number of events 2 • From start of study drug administration up to Day 13
|
|
Eye disorders
Dry eye
|
7.6%
6/79 • Number of events 6 • From start of study drug administration up to Day 13
|
2.6%
2/77 • Number of events 2 • From start of study drug administration up to Day 13
|
|
Eye disorders
Erythema of eyelid
|
0.00%
0/79 • From start of study drug administration up to Day 13
|
2.6%
2/77 • Number of events 2 • From start of study drug administration up to Day 13
|
|
General disorders
Instillation site pain
|
7.6%
6/79 • Number of events 6 • From start of study drug administration up to Day 13
|
3.9%
3/77 • Number of events 3 • From start of study drug administration up to Day 13
|
|
Infections and infestations
Conjunctivitis
|
6.3%
5/79 • Number of events 6 • From start of study drug administration up to Day 13
|
1.3%
1/77 • Number of events 1 • From start of study drug administration up to Day 13
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
- Publication restrictions are in place
Restriction type: OTHER