TLC599 in Patients With Osteoarthritis of the Knee

Table 1. Baseline demographic and clinical characteristics (safety population)
Characteristic	Statistics	Placebo (n = 25)	TLC599 12 mg (n = 26)	TLC599 18 mg (n = 24)
Age (years)	Mean (SD)	64.8 (8.45)	63.9 (9.07)	62.9 (8.80)
Gender
Male	n (%)	7 (28.0)	11 (42.3)	7 (29.2)
Female	n (%)	18 (72.0)	15 (57.7)	17 (70.8)
Race
Asian	n (%)	12 (48.0)	13 (50.0)	12 (50.0)
Australian aboriginal	n (%)	0	0	1 (4.2)
Caucasian	n (%)	13 (52.0)	13 (50.0)	11 (45.8)
Country
AU	n (%)	13 (52.0)	13 (50.0)	12 (50.0)
TW	n (%)	12 (48.0)	13 (50.0)	12 (50.0)
BMI (kg/m²)	Mean (SD)	27.93 (4.655)	27.65 (4.286)	27.96 (5.114)
Baseline VAS score (study knee)	Mean (SD)	6.56 (1.049)	6.45 (1.113)	6.87 (1.215)
Baseline WOMAC-Pain subscale score (0–4)	Mean (SD)	1.62 (0.609)	1.49 (0.558)	1.74 (0.631)
Baseline WOMAC-Function subscale score (0–4)	Mean (SD)	1.48 (0.652)	1.53 (0.531)	1.82 (0.742)
Knee pain
Bilateral	n (%)	15 (60.0)	16 (61.5)	15 (62.5)
Unilateral	n (%)	10 (40.0)	10 (38.5)	9 (37.5)
KL grade
2	n (%)	9 (36.0)	13 (50.0)	9 (37.5)
3	n (%)	16 (64.0)	13 (50.0)	15 (62.5)

AU Australia, BMI body mass index, n number of participants, SD standard deviation, TW Taiwan

Table 2. Statistical analysis on the mean change from baseline in WOMAC-Pain scores through scheduled visits
Interval	Treatment	Number	LS mean (SE)	90% CI	Difference vs placebo
Interval	Treatment	Number	LS mean (SE)	90% CI	LS mean (SE)	90% CI	p-value
D3 - W12	Placebo (N = 25)	25	− 0.47 (0.092)	(− 0.619, − 0.313)
	TLC599 12 mg (N = 26)	26	− 0.83 (0.090)	(− 0.984, − 0.685)	− 0.37 (0.129)	(− 0.583, − 0.154)	0.0027
	TLC599 18 mg (N = 24)	24	− 0.64 (0.094)	(− 0.794, − 0.481)	− 0.17 (0.131)	(− 0.390, 0.047)	0.0971
D3 - W16	Placebo (N =2 5)	25	− 0.48 (0.091)	(− 0.633, − 0.332)
	TLC599 12 mg (N = 26)	26	− 0.85 (0.088)	(− 0.999, − 0.705)	− 0.37 (0.127)	(− 0.580, − 0.158)	0.0024
	TLC599 18 mg (N = 24)	24	− 0.62 (0.093)	(− 0.772, − 0.463)	− 0.13 (0.129)	(− 0.350, 0.080)	0.1498
D3 - W20	Placebo (N = 25)	25	− 0.49 (0.091)	(− 0.647, − 0.343)
	TLC599 12 mg (N = 26)	26	− 0.85 (0.089)	(− 1.000, − 0.704)	− 0.36 (0.127)	(− 0.570, − 0.145)	0.0033
	TLC599 18 mg (N = 24)	24	− 0.63 (0.093)	(− 0.782, − 0.472)	− 0.13 (0.130)	(− 0.349, 0.084)	0.1558
D3 - W24	Placebo (N = 25)	25	− 0.51 (0.092)	(− 0.666, − 0.361)
	TLC599 12 mg (N = 26)	26	− 0.87 (0.089)	(− 1.014, − 0.718)	− 0.35 (0.128)	(− 0.565, − 0.139)	0.0037
	TLC599 18 mg (N = 24)	24	− 0.62 (0.093)	(− 0.780, − 0.469)	− 0.11 (0.130)	(− 0.328, 0.106)	0.1985

LS means, CIs, and p-values were obtained from an MMRM model including factors of treatment, visit, and baseline value as fixed factors, center as a random factor, and treatment by visit as interaction terms. CI confidence interval, D day, LS least squares, mITT modified intent to treat, MMRM mixed effect model repeat measurement, SE standard error, W week

Table 3. Frequent (> 5%) treatment-emergent adverse events (safety population)
AE category	Placebo (N = 25)	TLC599 12 mg (N = 26)	TLC599 18 mg (N = 24)
Any adverse event	17 (68%)	18 (69%)	20 (83%)
Headache	4 (16%)	3 (12%)	6 (25%)
Nasopharyngitis	3 (12%)	4 (15%)	1 (4%)
Cortisol decreased	0	2 (8%)	6 (25%)
Upper respiratory tract infection	2 (8%)	1 (4%)	4 (17%)
Arthralgia	3 (12%)	1 (4%)	2 (8%)
Glucocorticoid deficiency	0	3 (12%)	1 (4%)
Bronchitis	3 (12%)	0	0
Cough	0	0	2 (8%)
Diarrhea	0	3 (12%)	0
Dyspepsia	0	2 (8%)	0
Lipase increased	2 (8%)	0	1 (4%)
Toothache	1 (4%)	0	2 (8%)
Urinary tract infection	1 (4%)	2 (8%)	0
Chronic kidney disease	2 (8%)	0	0
Injury	2 (8%)	0	0

Authors and Disclosures

David J. Hunter^1,2, Chi-Ching Chang^3,4, James Cheng-Chung Wei^5–7, Hsiao-Yi Lin^8,9, Carl Brown¹⁰, Tien-Tzu Tai¹⁰, Chih-Feng Wu¹⁰, Wing Chia-Ming Chuang¹⁰ and Sheue-Fang Shih¹⁰*

¹Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, Australia. ²Rheumatology Department, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. ³Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan. ⁴Division of Rheumatology, Immunology and Allergy, Department of Internal Medicine, Taipei Medical University Hospital, Taipei City, Taiwan. ⁵Institute of Medicine, Chung Shan Medical University, Taichung City, Taiwan. ⁶Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung City, Taiwan. ⁷Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan. ⁸Department of Medicine, Cheng Hsin General Hospital, Taipei City, Taiwan. ⁹School of Medicine, National Yang-Ming University, Taipei City, Taiwan. ¹⁰Taiwan Liposome Company, Ltd., 2F, No. 3 Yuanqu St., Nangang Dist., Taipei City 115, Taiwan.

*Correspondence
yvonne@tlcbio.com

Authors' contributions
All authors participated in the interpretation of the study results and in the critical revision and approval of the final version of the manuscript. DH, CW, TT, and SS contributed to the study conception and design. CC, JW, and HL contributed to the acquisition of the study results. CB, CW, WC, and SS conducted the data analysis and manuscript drafting.

Competing interests
David J Hunter provides consulting advice to Merck Serono, Pfizer, Lilly, and TLCBio. James Cheng-Chung Wei received research grant, speaker fee, or advisor board from Pfizer, Abbott, Abbvie, Bristol-Myers Squibb, Eli Lilly, JNJ, UCB, MSD, GSK, Chugai, Roche, Celgene, Sanofi-Aventis, and Novartis. Sheue-Fang Shih, Carl Brown, Tien-Tzu Tai, and Wing Chia-Ming Chuang are employees and shareholders of the Taiwan Liposome Company. Chih-Feng Wu was an employee of Taiwan Liposome Company during the trial conduct but was no longer in the company at the time of this manuscript submission. The rest of the authors declare that they have no competing interests.