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Clinical trial of TK-98 on retinitis pigmentosa: A prospective, randomized, double-blind, placebo-controlled study (Clinical trial of TK-98 on retinitis pigmentosa)

Clinical trial of TK-98 on retinitis pigmentosa: A prospective, randomized, double-blind, placebo-controlled study (Clinical trial of TK-98 on retinitis pigmentosa)

70

Seventy patients with retinitis pigmentosa were included to this study. Forty-five patients (88 eyes) were randomly assigned to TK-98 group and 25 (46 eyes) were assigned to the placebo group. Average age at the time of inclusion was 51.7 and 51.6 y.o, femal ratio was 53.3% and 56.0% and time from onset of first subjective symptoms was 29.3 and 27.0 years, in TK-98 and placebo group respectively. EYS was found as the presumed causasive gene in 17.8% and 36.0% in TK-98 and placebo group respectively.

Seventy patients were included to this study. Forty-five patients were assigned to TK-98 group and 25 patients were assigned to placebo group. Two patients in the TK-98 group discontinued the trial due to personal reasons, and other 68 patients completed the 78 weeks administration. All 70 patients were analyzed in Safety Analysis Set (SAF) and in Full Analysis Set (FAS). One patient who had the administration of the study drug less than 53 weeks was excluded from the analysis in Per Protocol Set (PPS).

Possible side effects related to the investigational drug were observed in three patients (6.7%) in the TK-98 group and two patients (8.0%) in the placebo group, which were abdominal distension in 2 patients (4.4%) and constipation in 1 patient (2.2%) in TK-98 group, and abdominal distension in 1 patient (4.0%) and gastroesophageal reflux disease in 1 patient (4.0%) in placebo group. The severity of the gastroesophageal reflux disease (1 patient, 4.0%) occurred in the placebo group was moderate, and all other possible side effects symptoms were mild. Serious adverse events were observed in 4 patients (8.9%) in TK-98 group and 2 patients (8.0%) in placebo group, which were ruled out to be associated with drug administration. No death of the subject occurred in this study.

There was no significant difference in the rate of change in the total point score(TPS), the primary endpoint, between the TK-98 and placebo groups (p = 0.58). Stratified analysis for the primary endpoint showed that several strata (TPS value of Humphrey visual field test 30-2 at the time of allocation <400 dB, age equal or older than 50 years, time from onset of first subjective symptoms equal or longer than 30 years, male, has a history of smoking, causative gene of EYS) showed tendencies that the TK-98 group had less deterioration, although none of the differences were statistically significant. TK-98 group showed slower decrease of ellipsoid zone length although the difference was not statistically significant.

This double-blind, randomized, placebo-controlled study aimed to investigate the efficaccy and safety of orally administered branched-chain amino acids (TK-98) on disease progression in patients with retinitis pigmentosa (RP). Seventy patients with RP were assigned to the TK-98 (45 patients) or placebo (25 patients) group. There was no significant difference in the rate of change in the total point score, the primary endpoint, between the TK-98 and placebo groups.

Oct. 01, 2024

Aug. 16, 2024

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11343008/pdf/tvst-13-8-29.pdf

No

https://jrct.niph.go.jp/latest-detail/jRCT2051180072

Ikeda Hanako

Kyoto University Hospital

54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto

rpkyoto@kuhp.kyoto-u.ac.jp

Hasegawa Tomoko

Kyoto University Hospital

54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto

+81-75-751-3727

rpkyoto@kuhp.kyoto-u.ac.jp

Complete

Mar. 01, 2019

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

1) patients diagnosed with typical retinitis pigmentosa
2) 20 years of age or older at the time of informed consent
3) written informed consent for inclusion in the clinical trial was obtained from the patient himself/herself

1) Both eyes with any of the following conditions (a-f).
a) A difference of > 5.0 dB in the MD value between consecutive Humphrey 10-2 visual field tests on at least two occasions (the most recent and 4 or more visual field tests performed within the last 3 years [but not less than 1 year] are analyzed)
b) MD value of the Humphrey 10-2 visual field test at screening > -5.0 dB or < -25.0 dB
c) Opacity of the optic media, which makes it difficult to examine the fundus
d) Nuclear cataract (Emery-Little grade 3 or more) or posterior subcapsular cataract that has progressed within a period of one year prior to the date of informed consent
e) Evidence of glaucoma, optic nerve disease, or vitreoretinal disease other than that concomitant to retinitis pigmentosa
f) History of intraocular surgery, other than cataract surgery
2) Best corrected decimal visual acuity < 0.01 or MD value of the Humphrey visual field test (10-2) < -30.0 dB in either eye
3) Systematic administration of immunosuppressive agents, anti-cancer chemotherapy, or steroids
4) Oral administration of calcium channel blockers or sodium valproate
5) Oral administration of dark adaptation-improving drugs, or drugs or supplements including (other than as an additive) vitamin A, vitamin E, DHA, taurine, lutein, or amino acids
6) Use of topical isopropyl unoprostone or brimonidine tartrate
7) Female patient who is pregnant, lactating, has child-bearing potential (pregnancy test is carried out at screening), or has a desire for bearing a child during the period from the date of informed consent to 2 weeks after the last investigational drug administration or 2 weeks after the day of discontinuation, or who has child-bearing potential but refuses to use appropriate contraception (intrauterine contraceptive devices, pessary, or the use of a condom sheath by her partner)
8) Patients under treatment for critical liver, respiratory, hematologic, or neurological disorders
9) Patients with renal failure (serum creatinine of 2.0 mg/dL or more)
10) Congenital dysbolism of branched-chain amino acids
11) History of shock or allergy to branched-chain amino acids
12) Patients who have participated in other interventional clinical trials within 6 months prior to the date of informed consent
13) Patients determined to be inappropriate for inclusion in the clinical trial by the principal investigator or sub-investigators

Both

retinitis pigmentosa

Investigational drug (TK-99 or placebo) administration: one packet after every meal (thrice a day)

retinitis pigmentosa

branched-chain amino acids

Total point score calculated as the sum of visual sensitivities at all locations measured by the Humphrey visual field test (10-2)

1) MD value, average sensitivity of central 4, 12, and 24 points, and foveal threshold on the Humphrey visual field test (10-2)
2) Total point score, average sensitivity of central 4, 12 and 24 points, and foveal threshold on the Humphrey visual field test (30-2)
3) Total retinal thickness, retinal volume, and ellipsoid zone length measured on optical coherence tomography
4) Readable letter numbers on the ETDRS visual acuity test chart
5) logMAR of ETDRS visual acuity
6) logMAR of decimal visual acuity
7) Proportion of eyes with relatively stable visual fields compared to the predicted value during the study period
8) Proportion of eyes with relatively stable visual acuity (visual acuity deterioration of logMAR 0.2 or less) during the study period
9) Macular area with normal retinal appearance
10) Frequency of adverse events and side effect expression

+81-75-751-4389

Jan. 31, 2019

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