parallel randomized trial

NCT05680155

A Phase 3, Multi-center, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety of XW003 in Patients With T2DM Inadequately Controlled by Diet and Exercise Alone

Type 2 diabetes (adults)NCT05680155S001967

Design

Randomized: 211
Start year: 2022
Treatment: 24 weeks, follow-up 24 weeks
Countries: China (32 sites)
Sponsor: Hangzhou Sciwind Biosciences Co., Ltd. (industry)
Eligibility: age 18 to 75; BMI 20.0 to 35.0; HbA1c 7.5 to 11.0 at screening and 7.0 to 10.5 at randomization; diet and exercise or one OHA stopped before screening

Conduct and analysis

Blinding: double blind
Sequence generation: other adequate
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: treatment policy
Analysis population: full analysis
Missing data: MMRM with retrieved dropout multiple imputation

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	ecnoglutide Ecnoglutide 1.2 mg	none; diet and exercise, prior single oral agent stopped before screening; lifestyle: standard	71	71	67
A2	ecnoglutide Ecnoglutide 0.6 mg	none; diet and exercise, prior single oral agent stopped before screening; lifestyle: standard	69	69	66
A3	Placebo Placebo (pooled volume matched)	none; diet and exercise, prior single oral agent stopped before screening; lifestyle: standard	71	71

Baseline characteristics

As printed in the trial reports or registry, per arm or for the whole trial.

Characteristic	Statistic	Ecnoglutide 1.2 mg A1	Ecnoglutide 0.6 mg A2	Placebo A3	Whole trial ALL
age	mean (years)	52.5	52.1	51.4
age	sd (years)	11.5	10.8	10.4
bmi	mean (kg/m2)	26.35	27.23	27.23
bmi	sd (kg/m2)	3.31	3.65	3.20
diabetes duration	mean (years)	3.66	4.10	3.00
diabetes duration	sd (years)	3.99	4.20	3.02
egfr	mean (mL/min/1.73 m2)	124.7	121.9	113.5
egfr	sd (mL/min/1.73 m2)	35.1	29.9	25.9
female	n	28	30	26
female	percent	39	43	37
hba1c: 8.5 or less	n	38	36	37
hba1c: 8.5 or less	percent	54	52	52
hba1c: more than 8.5	n	33	33	34
hba1c: more than 8.5	percent	46	48	48
hba1c	mean (percent)	8.51	8.54	8.51
hba1c	sd (percent)	0.83	0.80	0.81
other ethnicity han	percent				99.1
sbp	mean (mmHg)	124.1	124.0	122.0
sbp	sd (mmHg)	12.81	12.95	13.30
waist	mean (cm)	93.26	94.02	94.60
waist	sd (cm)	8.94	10.55	8.36
weight	mean (kg)	71.53	74.25	73.69
weight	sd (kg)	12.05	15.20	11.31

Results

102 adjudicated result lines, grouped by outcome. Open an outcome to see its values.

HbA1c change (43 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
24	A1	change	-2.43 percent		-2.65 to -2.20	71	treatment policy; full analysis; R0007432:Table 2
24	A1	change	-2.43 percent		-2.65 to -2.20		hypothetical; full analysis; R0007432:Results
24	A1	change	-2.40 percent	1.109			not stated; other; R0007432:Peer review file Table R1
24	A1 vs A3	md	-1.564 percent		-1.863 to -1.265		not stated; full analysis; R0007432:Supplementary Fig 3
24	A1 vs A3	md	-1.460 percent		-1.777 to -1.142		not stated; full analysis; R0007432:Supplementary Fig 3
24	A1 vs A3	md	-1.58 percent		-1.90 to -1.26		hypothetical; full analysis; R0007432:Results
24	A1 vs A3	md	-1.56 percent		-1.87 to -1.24		treatment policy; full analysis; R0007432:Table 2
24	A1 vs A3	md	-1.102 percent		-2.045 to -0.160		treatment policy; full analysis; age:65_or_older; R0007432:Supplementary Fig 4
24	A1 vs A3	md	-1.644 percent		-1.981 to -1.308		treatment policy; full analysis; age:less_than_65; R0007432:Supplementary Fig 4
24	A1 vs A3	md	-1.374 percent		-1.785 to -0.963		treatment policy; full analysis; background:no_prior_oha; R0007432:Supplementary Fig 4
24	A1 vs A3	md	-1.760 percent		-2.338 to -1.181		treatment policy; full analysis; background:prior_oha_more_than_12_weeks; R0007432:Supplementary Fig 4
24	A1 vs A3	md	-1.922 percent		-2.793 to -1.051		treatment policy; full analysis; background:prior_oha_within_12_weeks; R0007432:Supplementary Fig 4
24	A1 vs A3	md	-1.759 percent		-2.265 to -1.253		treatment policy; full analysis; bmi:24_to_28; R0007432:Supplementary Fig 4
24	A1 vs A3	md	-1.315 percent		-1.836 to -0.794		treatment policy; full analysis; bmi:28_or_more; R0007432:Supplementary Fig 4
24	A1 vs A3	md	-1.661 percent		-2.358 to -0.965		treatment policy; full analysis; bmi:less_than_24; R0007432:Supplementary Fig 4
24	A1 vs A3	md	-1.560 percent		-1.875 to -1.245		treatment policy; full analysis; egfr:60_or_more; R0007432:Supplementary Fig 4
24	A1 vs A3	md	-1.380 percent		-1.715 to -1.046		treatment policy; full analysis; hba1c:8.5_or_less; R0007432:Supplementary Fig 4
24	A1 vs A3	md	-1.771 percent		-2.282 to -1.260		treatment policy; full analysis; hba1c:more_than_8.5; R0007432:Supplementary Fig 4
24	A1 vs A3	md	-1.632 percent		-2.119 to -1.145		treatment policy; full analysis; sex:female; R0007432:Supplementary Fig 4
24	A1 vs A3	md	-1.471 percent		-1.881 to -1.061		treatment policy; full analysis; sex:male; R0007432:Supplementary Fig 4
24	A2 vs A3	md	-1.434 percent		-1.946 to -0.921		treatment policy; full analysis; hba1c:more_than_8.5; R0007432:Supplementary Fig 4
24	A2 vs A3	md	-1.473 percent		-2.244 to -0.702		treatment policy; full analysis; bmi:less_than_24; R0007432:Supplementary Fig 4
24	A2 vs A3	md	-1.075 percent		-1.393 to -0.758		treatment policy; full analysis; egfr:60_or_more; R0007432:Supplementary Fig 4
24	A2	change	-1.91 percent	1.060			not stated; other; R0007432:Peer review file Table R1
24	A2 vs A3	md	-1.088 percent		-1.388 to -0.787		not stated; full analysis; R0007432:Supplementary Fig 3
24	A2 vs A3	md	-1.040 percent		-1.359 to -0.721		not stated; full analysis; R0007432:Supplementary Fig 3
24	A2 vs A3	md	-0.788 percent		-1.125 to -0.451		treatment policy; full analysis; hba1c:8.5_or_less; R0007432:Supplementary Fig 4
24	A2	change	-1.96 percent		-2.18 to -1.73	69	treatment policy; full analysis; R0007432:Table 2
24	A2 vs A3	md	-1.09 percent		-1.40 to -0.77		treatment policy; full analysis; R0007432:Table 2
24	A2 vs A3	md	-0.655 percent		-1.875 to 0.566		treatment policy; full analysis; age:65_or_older; R0007432:Supplementary Fig 4
24	A2 vs A3	md	-1.124 percent		-1.449 to -0.799		treatment policy; full analysis; age:less_than_65; R0007432:Supplementary Fig 4
24	A2 vs A3	md	-1.061 percent		-1.508 to -0.614		treatment policy; full analysis; background:no_prior_oha; R0007432:Supplementary Fig 4
24	A2 vs A3	md	-1.315 percent		-1.794 to -0.835		treatment policy; full analysis; sex:female; R0007432:Supplementary Fig 4
24	A2 vs A3	md	-1.089 percent		-1.634 to -0.545		treatment policy; full analysis; background:prior_oha_more_than_12_weeks; R0007432:Supplementary Fig 4
24	A2 vs A3	md	-1.473 percent		-2.361 to -0.585		treatment policy; full analysis; background:prior_oha_within_12_weeks; R0007432:Supplementary Fig 4
24	A2 vs A3	md	-0.931 percent		-1.349 to -0.513		treatment policy; full analysis; sex:male; R0007432:Supplementary Fig 4
24	A2 vs A3	md	-1.205 percent		-1.688 to -0.723		treatment policy; full analysis; bmi:24_to_28; R0007432:Supplementary Fig 4
24	A2 vs A3	md	-0.804 percent		-1.315 to -0.293		treatment policy; full analysis; bmi:28_or_more; R0007432:Supplementary Fig 4
24	A2	change	-1.96 percent		-2.18 to -1.73		hypothetical; full analysis; R0007432:Results
24	A2 vs A3	md	-1.11 percent		-1.43 to -0.79		hypothetical; full analysis; R0007432:Results
24	A3	change	-0.88 percent	0.794			not stated; other; R0007432:Peer review file Table R1
24	A3	change	-0.85 percent		-1.07 to -0.62		hypothetical; full analysis; R0007432:Results
24	A3	change	-0.87 percent		-1.09 to -0.65	71	treatment policy; full analysis; R0007432:Table 2

Body weight change in kilograms (diabetes) (5 lines; O02)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
24	A1 vs A3	md	-1.76 kg	-2.65 to -0.87		treatment policy; full analysis; R0007432:Table 2
24	A1	change	-3.21 kg	-3.84 to -2.58	71	treatment policy; full analysis; R0007432:Table 2
24	A2 vs A3	md	-1.59 kg	-2.48 to -0.69		treatment policy; full analysis; R0007432:Table 2
24	A2	change	-3.04 kg	-3.68 to -2.40	69	treatment policy; full analysis; R0007432:Table 2
24	A3	change	-1.45 kg	-2.08 to -0.82	71	treatment policy; full analysis; R0007432:Table 2

HbA1c below 7 percent (5 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
24	A1	responders	80.3		57 / 71	not stated; full analysis; R0007432:Results
24	A1 vs A3	or	17.96	7.582 to 42.523		not stated; full analysis; R0007432:Supplementary Table 1
24	A2 vs A3	or	9.22	4.128 to 20.574		not stated; full analysis; R0007432:Supplementary Table 1
24	A2	responders	68.1		47 / 69	not stated; full analysis; R0007432:Results
24	A3	responders	21.1		15 / 71	not stated; full analysis; R0007432:Results

Level 2 or 3 hypoglycemia (participants) (9 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	0 / 71	not stated; safety; R0004215:Table 3 p14
A1	events	4 / 71	not stated; safety; R0007432:Table 3
A1	events	0 / 71	not stated; safety; R0004215:Table 3 p14
A2	events	2 / 69	not stated; safety; R0007432:Table 3
A2	events	0 / 69	not stated; safety; R0004215:Table 3 p14
A2	events	0 / 69	not stated; safety; R0004215:Table 3 p14
A3	events	0 / 71	not stated; safety; R0004215:Table 3 p14
A3	events	0 / 71	not stated; safety; R0004215:Table 3 p14
A3	events	1 / 71	not stated; safety; R0007432:Table 3

Systolic blood pressure change (3 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	Detail
24	A1	change	-5.2 mmHg	12.00	not stated; other; R0007432:Supplement Table 3
24	A2	change	-4.4 mmHg	13.37	not stated; other; R0007432:Supplement Table 3
24	A3	change	-2.1 mmHg	13.40	not stated; other; R0007432:Supplement Table 3

Percent body weight change (5 lines; O10)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
24	A1	percent change	-4.74 percent	-5.65 to -3.82	71	treatment policy; full analysis; R0007432:Table 2
24	A1 vs A3	md	-2.72 percent	-4.01 to -1.43		treatment policy; full analysis; R0007432:Table 2
24	A2	percent change	-4.51 percent	-5.43 to -3.58	69	treatment policy; full analysis; R0007432:Table 2
24	A2 vs A3	md	-2.49 percent	-3.79 to -1.20		treatment policy; full analysis; R0007432:Table 2
24	A3	percent change	-2.02 percent	-2.92 to -1.11	71	treatment policy; full analysis; R0007432:Table 2

Weight loss of 5 percent or more (5 lines; O11A)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
24	A1	responders	43.7		31 / 71	not stated; full analysis; R0007432:Results
24	A1 vs A3	or	6.20	2.498 to 15.401		not stated; full analysis; R0007432:Supplementary Table 1
24	A2	responders	39.1		27 / 69	not stated; full analysis; R0007432:Results
24	A2 vs A3	or	5.73	2.267 to 14.503		not stated; full analysis; R0007432:Supplementary Table 1
24	A3	responders	11.3		8 / 71	not stated; full analysis; R0007432:Results

Weight loss of 10 percent or more (5 lines; O11B)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
24	A1	responders	9.9		7 / 71	not stated; full analysis; R0007432:Supplement Table 1
24	A1 vs A3	or	6.93	0.821 to 58.441		not stated; full analysis; R0007432:Supplementary Table 1
24	A2	responders	10.1		7 / 69	not stated; full analysis; R0007432:Supplement Table 1
24	A2 vs A3	or	7.64	0.904 to 64.557		not stated; full analysis; R0007432:Supplementary Table 1
24	A3	responders	1.4		1 / 71	not stated; full analysis; R0007432:Supplement Table 1

All cause mortality (3 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 71	not stated; safety; R0007432:Table 3
A2	events	0 / 69	not stated; safety; R0007432:Table 3
A3	events	0 / 71	not stated; safety; R0007432:Table 3

Serious adverse events (3 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	3 / 71	not stated; safety; R0007432:Table 3
A2	events	2 / 69	not stated; safety; R0007432:Table 3
A3	events	4 / 71	not stated; safety; R0007432:Table 3

Discontinuation due to adverse events (3 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	1 / 71	not stated; safety; R0007432:Table 3
A2	events	1 / 69	not stated; safety; R0007432:Table 3
A3	events	1 / 71	not stated; safety; R0007432:Table 3

Nausea (3 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	9 / 71	not stated; safety; R0007432:Table 3
A2	events	5 / 69	not stated; safety; R0007432:Table 3
A3	events	7 / 71	not stated; safety; R0007432:Table 3

Diarrhea (3 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	8 / 71	not stated; safety; R0007432:Table 3
A2	events	17 / 69	not stated; safety; R0007432:Table 3
A3	events	4 / 71	not stated; safety; R0007432:Table 3

Gallbladder and biliary disease (2 lines; O28)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 71	not stated; safety; R0007432:Results
	A2	events				0 / 69	not stated; safety; R0007432:Results

Acute pancreatitis (2 lines; O29)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 71	not stated; safety; R0007432:Results
	A2	events				0 / 69	not stated; safety; R0007432:Results

Death by suicide (3 lines; O35B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 71	not stated; safety; R0007432:Table 3
A2	events	0 / 69	not stated; safety; R0007432:Table 3
A3	events	0 / 71	not stated; safety; R0007432:Table 3