A 12-week, randomized, double-blind, placebo-controlled study assessing the efficacy of EGHB010, a standardized extract of Paeoniae radix and Glycyrrhizae radix, in patients with early age-related macular degeneration
KCT0005342 | Not reported | Kim JY et al. (2021)
Kim, J. Y., Kim, M., Kim, R. Y., Park, W. K., Park, Y. H. A 12-week, randomized, double-blind, placebo-controlled study assessing the efficacy of EGHB010, a standardized extract of Paeoniae radix and Glycyrrhizae radix, in patients with early age-related macular degeneration. Ann Transl Med, 2021; 9(7):541.
Locations
Single center in South Korea
Study Period
October 13, 2017 – June 28, 2019
Study Design
Randomized, double-blind, placebo-controlled, single-center trial
Study Population
Experimental Group
Control Group
Follow-up Time: 12 Weeks
Outcomes
Durability
Not reported
Vision
Amplitude and Latency of Electroretinography (ERG)
The mean ERG a-wave amplitude change at 12 weeks from baseline:
• Treatment = +1.66±47.08 µV (p=0.9594)
• Control = +11.59 ± 23.98 µV (p=0.6238)
• Wilcoxon’s rank-sum test for the difference between groups (p = 0.9638)
The mean ERG b-wave amplitude change at 12 weeks from baseline:
• Treatment = –0.44±74.68 µV (p=0.6420)
• Control = –7.86±60.89 µV (p=0.1046)
• Wilcoxon’s rank-sum test for the difference between groups (p = 0.3716)
The mean ERG implicit time change at 12 weeks from baseline:
• Treatment = 0.78±9.56 ms (p=0.6391)
• Control = 0.78±8.00 ms (p=0.6094)
• Wilcoxon’s rank-sum test for the difference between groups (p = 0.8052)
Other
N/A
Immunognicity
Not reported
Pharmokinetics
Not reported
Anatomic
Macular Pigment Optical Density (1°) (MPOD)
The mean MPOD change at 12 weeks from baseline (Primary Outcome):
• Treatment = +0.04 ± 0.27 (p = 0.2730)
• Control = -0.03 ± 0.21 (p = 0.7240)
• Independent t-test for the difference between groups (p = 0.1234).
Subgroup (MPOD <0.75 at baseline):
• Treatment = +0.09 ± 0.25 (p = 0.0218)
• Control = +0.02 ± 0.16 (p = 0.5605)
• Wilcoxon’s rank-sum test for the difference between groups (p = 0.0248)
Central Macular Thickness (CMT)
Mean CMT change at 12 weeks from baseline:
• Treatment = +15.08 ± 19.26 µm (p<0.0001)
• Control = +11.59 ± 23.98 µm (p=0.0033)
• Wilcoxon’s rank-sum test for the difference between groups (p = 0.6718)
Subgroup (MPOD <0.75 at baseline):
• Treatment = +16.23±18.28 µm (p<0.0001)
• Control = +10.94±25.37 µm (p=0.0167)
• Wilcoxon’s rank-sum test for the difference between groups (p = 0.1061)
Central Choroidal Thickness (CCT) Mean CCT change at 12 weeks from baseline:
• Treatment = +19.50 ± 46.54 µm (p= 0.0056)
• Control = +10.20 ± 39.02 µm (p= 0.0831)
• Independent t-test for the difference between groups (p = 0.6608)
Subgroup (MPOD <0.75 at baseline):
• Treatment = +20.13±48.17 µm (p= 0.0129)
• Control = +10.83±40.00 µm (p= 0.1131)
• Independent t-test for the difference between groups (p = 0.3685)
Safety
AEs
Patients with mild adverse reactions:
• Treatment: 23/48 (47.9%)
• Control: 18/46 (39.1%)
• Difference in the incidence of adverse events: p = 0.3905
Serious AEs (SAEs)
No serious drug-related adverse reactions were noted.
Ocular-related AEs (Study Eye)
Not reported
Non-ocular AEs
Cough:
• Treatment: 8/48 (16.67%)
• Control: 4/46 (8.70%)
Nasopharyngitis:
• Treatment: 5/48 (10.42%)
• Control: 3/46 (6.52%)
Back pain:
• Treatment: 3/48 (6.25%)
• Control: 0
Gastritis:
• Treatment: 2/48 (4.17%)
• Control: 2/46 (4.35%)
Headache:
• Treatment: 2/48 (4.17%)
• Control: 2/46 (4.35%)
Musculoskeletal pain:
• Treatment: 2/48 (4.17%)
• Control: 0
Rash (2.08%, 1 case)
• Treatment: 1/48 (2.08%)
• Control: 3/46 (6.52%)
Oropharyngeal pain (2.08%, 1 case)
• Treatment: 1/48 (2.08%)
• Control: 0
Nausea:
• Treatment: 1/48 (2.08%)
• Control: 1/46 (2.17%)
Cystitis:
• Treatment: 1/48 (2.08%)
• Control: 1/46 (2.17%)
Hematuria:
• Treatment: 1/48 (2.08%)
• Control: 1/46 (2.17%)
Dental caries:
• Treatment: 1/48 (2.08%)
• Control: 1/46 (2.17%)
Hemorrhoid:
• Treatment: 1/48 (2.08%)
• Control: 0
General weakness:
• Treatment: 1/48 (2.08%)
• Control: 0
Hiatal hernia:
• Treatment: 1/48 (2.08%)
• Control: 0
Colitis:
• Treatment: 1/48 (2.08%)
• Control: 0
Rotator cuff syndrome:
• Treatment: 1/48 (2.08%)
• Control: 0
Depression:
• Treatment: 1/48 (2.08%)
• Control: 0
Dyspepsia:
• Treatment: 0
• Control: 3/46 (6.52%)
Glare and halo (4.35%, 2 cases)
• Treatment: 0
• Control: 2/46 (4.35%)
Influenza:
• Treatment: 0
• Control: 1/46 (2.17%)
Dysuria:
• Treatment: 0
• Control: 1/46 (2.17%)
Gout:
• Treatment: 0
• Control: 1/46 (2.17%)
Sleep disorder:
• Treatment: 0
• Control: 1/46 (2.17%)
Conclusion
EGHB010 may increase MPOD in subjects with lower baseline MPOD (<0.75), with no serious adverse events reported. Further research is needed to confirm long-term effects.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Low risk
Note: “For randomization, a statistical expert independent of this study generated a randomization number using SAS ver..9.4 (SAS Institute Inc., NC, Cary, USA)”
There is no statistical difference in baseline characteristics for the treatment group and control group (Table 2).
Missing Outcome Data
Some concerns
Note: The total missingness was (11/94%=11.7%). There is no evidence that the result was not biased by missing outcome data.
However, it is unlikely that missingness in the outcome depended on its true value.
Selection of the Reported Results
Low risk Registration with the protocol.
Deviations from Intended Observations
Low risk Note: this is a double-blind study. According to Table 3, the ITT principle was applied for the primary outcome analysis.
Measurement of the Outcome
Low risk This is a double-blind study on a single site.
Overall
Some concerns
Categories: Dry AMD