Assessment of real-life patient handling experience of AVT02 administered subcutaneously via autoinjector in patients with moderate to severe active rheumatoid arthritis: an open-label, single-arm clinical trial, then an extension phase of AVT02 administered with a prefilled syringe

Figures & data

Figure 1. Patient disposition. *One patient was initially enrolled and received a dose of AVT02, and subsequently withdrew due to a positive Hepatitis B surface antigen at screening.

Table 1. Baseline characteristics (Safety population).

Characteristic	AVT02-AI N = 107
Age; mean ± SD, years	54.4 ± 11.1
Male/Female; %	10.3/89.7
Weight; mean ± SD, kg	72.9 ± 16.0
Height; mean ± SD, cm	165.9 ± 6.6
BMI; mean ± SD, kg/m^2	26.5 ± 5.6
Race; n (%)
White	107 (100.0)
Ethnicity; n (%)
Hispanic/Latino	2 (1.9)
Not Hispanic/Latino	105 (98.1)
Time from RA diagnosis; mean ± SD, months	125.2 ± 89.7
Tender Joint Count; mean ± SD	19.7 ± 5.6
Swollen Joint Count; mean ± SD, months	16.8 ± 5.3
Disease Activity Score-28; mean ± SD	6.7 ± 0.8
Methotrexate dose; mean ± SD, mg/week	14.1 ± 1.7
Rheumatoid Factor; mean ± SD	182.4 ± 186.9
Prior medications (≥1%); n (%)	5 (4.7)
Immunosuppressants	3 (2.8)
Anti-inflammatory and anti-rheumatic products	2 (1.9)
Blood substitutes and perfusion solutions	2 (1.9)
Corticosteroids for systemic use	2 (1.9)
Concomitant medications (≥10%); n (%)	107 (100.0)
Immunosuppressants	107 (100.0)
Anti-anemic preparations	106 (99.1)
Corticosteroids for systemic use	91 (85.0)
Anti-inflammatory and anti-rheumatic products	60 (56.1)
Drugs for acid-related disorders	28 (26.2)
Diuretics	26 (24.3)
Agents acting on the renin-angiotensin system	14 (13.1)
Vitamins	14 (13.1)

BMI: body mass index; RA: rheumatoid arthritis; SD: standard deviation.

Table 2. AI performance (Full analysis population).

AVT02-AI N = 107
Visit	n	Injection success, % (95% Wilson score CI)
OAT
Week 4*	105	100.0 (96.5, 100.0)
Week 6	106	100.0 (96.5, 100.0)
Week 8	106	100.0 (96.5, 100.0)
Overall*	317	100.0 (98.8, 100.0)
PAT
Week 4*	105	100.0 (96.5, 100.0)
Week 6	106	100.0 (96.5, 100.0)
Week 8	106	100.0 (96.5, 100.0)
Overall*	317	100.0 (98.8, 100.0)

*One patient missed one dose at Week 4; AI: autoinjector; CI: confidence interval; OAT: observer assessment tool; PAT: participant assessment tool.

Table 3. Ease of use of the AI (Full analysis population).

AVT02-AI N = 107
	Week 2, n (%)	Week 4, n (%)	Week 6, n (%)	Week 8, n (%)
Overall, do you feel that the instructions provided for this injector were useful?
Very useful	97 (91.5)	97 (92.4)	97 (91.5)	97 (91.5)
Somewhat useful	9 (8.5)	8 (7.6)	9 (8.5)	9 (8.5)
Not very useful	0	0	0	0
Not useful at all	0	0	0	0
Overall, do you feel that the instructions were generally clear, or not?
Very clear	94 (88.7)	95 (90.5)	91 (85.8)	95 (89.6)
Somewhat clear	12 (11.3)	10 (9.5)	15 (14.2)	11 (10.4)
Not very clear	0	0	0	0
Not clear at all	0	0	0	0
Do you feel that any particular step (or more than 1 step) was really difficult?
No steps were really difficult	86 (81.1)	89 (84.8)	92 (86.8)	91 (85.8)
Getting ready	11 (10.4)	7 (6.7)	5 (4.7)	7 (6.6)
Selecting an injection area	6 (5.7)	4 (3.8)	4 (3.8)	7 (6.6)
Preparing the injector	3 (2.8)	0	1 (0.9)	2 (1.9)
Activating the injector	7 (6.6)	5 (4.8)	4 (3.8)	3 (2.8)
Injecting the dose	1 (0.9)	1 (1.0)	0	0
Other	0	0	0	0
Apart from the instructions, and thinking about the design of the injector itself, do you think the injector is generally easy to use, or generally difficult to use?
Very easy	85 (80.2)	82 (78.1)	88 (83.0)	90 (84.9)
Somewhat easy	20 (18.9)	21 (20.0)	17 (16.0)	15 (14.2)
Somewhat difficult	1 (0.9)	2 (1.9)	1 (0.9)	1 (0.9)
Very difficult	0	0	0	0

AI: autoinjector.

Figure 2. Mean (± SE) of SDAI Score from baseline by visit (Full analysis set).

Baseline: N = 107. Week 4–56: N = 106. SDAI: Simple Disease Activity Index; SE: standard error.

Figure 3. Mean (± SE) of DAS28 CRP from baseline by visit (Full analysis set).

Baseline: N = 107. Week 4–56: N = 106. DAS28 CRP: Disease Activity Score 28 C-reactive protein; SE: standard error.

Table 4. ACR-20/-50/-70 response (Full analysis population).

AVT02 N = 107*
Visit	Achieved response, % (95% CI)
	ACR20 response	ACR50 response	ACR70 response
Week 4	24.5 (17.3, 33.5)	2.8 (1.0, 8.0)	0.9 (0.2, 5.2)
Week 8	49.1 (39.7, 58.4)	5.7 (2.6, 11.8)	0.9 (0.2, 5.2)
Week 14	72.6 (63.5, 80.2)	32.1 (24.0, 41.5)	1.9 (0.5, 6.6)
Week 24	62.3 (52.8, 70.9)	36.8 (28.2, 46.3)	5.7 (2.6, 11.8)
Week 36	66.0 (56.6, 74.4)	39.6 (30.8, 49.1)	13.2 (8.0, 21.0)
Week 56	70.8 (61.5, 78.6)	47.2 (37.9, 56.6)	13.2 (8.0, 21.0)

*N = 107 for Weeks 4 and 8; N = 106 for Weeks 14, 24, 36 and 56. ACR: American College of Rheumatology; AI: autoinjector; CI: confidence interval.

Figure 4. Mean (± SD) AVT02 serum concentration from baseline by visit (Safety set).

”LLOQ” values are replaced for the calculations with 0.5*LLOQ. LLOQ = 150 ng/mL. BL to Week 2; N = 107. Week 8–36; N = 106. BL: baseline; SD: standard deviation.

Table 5. Safety (Safety population).

Parameter	Active Phase AVT02-AI (N = 107)		Extension Phase AVT02-PFS (N = 106)
	Patients, n (%)	Events, n	Patients, n (%)	Events, n
Patients with 1≥ TEAE	20 (18.7)	24	32 (30.2)	43
Patients with 1≥ treatment-related TEAE	3 (2.8)	3	2 (1.9)	2
Maximum severity of TEAEs
Mild	12 (11.2)	N/A	20 (18.9)	N/A
Moderate	7 (6.5)	N/A	11 (10.4)	N/A
Severe	1 (0.9)	N/A	1 (0.9)	N/A
Patients with 1≥ serious TEAE	0	0	2 (1.9)	3
Patients with 1≥ treatment-related serious TEAE	0	0	1 (0.9)	1
Patients with 1≥ TEAESI*	1 (0.9)	1	4 (3.8)	4
TEAE by system organ class, preferred term^†
Blood and lymphatic system disorders	0	0	5 (4.7)	5
Anemia	0	0	5 (4.7)	5
Injection-site reaction	0	0	0	0
Infections and infestations	9 (8.4)	9	5 (4.7)	5
COVID-19	0	0	3 (2.8)	3
Influenza	5 (4.7)	5	0	0
Investigations	0	0	6 (5.7)	6
Musculoskeletal and connective tissue disorders	0	0	6 (5.7)	6
Nervous system disorders	3 (2.8)	3	4 (3.8)	5
Headache	3 (2.8)	3	3 (2.8)	3

*TEAESI included leukopenia, liver enzyme abnormalities, and mycobacterium tuberculosis complex test positive. ^†TEAE frequency ≥2%. Patients are counted once within a system organ class and once for each unique preferred term. AI: autoinjector; COVID-19: coronavirus disease; N/A: not applicable; PFS: pre-filled syringe; TEAE; treatment-emergent adverse event; TEAESI: treatment-emergent adverse event of special interest.

Data availability statement

The datasets generated and/or analyzed during the current study are available from the sponsor on reasonable request.