A Two-Stage Study of the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics and Immunogenicity of Various Doses of Levilimab When Administered Intravenously and Subcutaneously to Healthy Subjects and Subjects With Active Rheumatoid Arthritis

Phase 3

Active, not recruiting

• Conditions: Rheumatoid Arthritis
• Interventions: Drug: Levilimab

• Registration Number: NCT05800327
• Lead Sponsor: Biocad

Brief Summary

This is a two-stage study of efficacy, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of various doses of levilimab when administered intravenously and subcutaneously to healthy subjects and subjects with active rheumatoid arthritis resistant to methotrexate monotherapy.

Aim of the Stage 1 is to study the tolerability, safety, immunogenicity, and main pharmacokinetic and pharmacodynamic parameters of levilimab after its single subcutaneous or intravenous administration at ascending doses to healthy subjects.

Aim of the Stage 2 is to confirm the efficacy and safety of levilimab 648 mg IV Q4W in combination with methotrexate and levilimab 324 mg SC Q2W in combination with methotrexate in subjects with active rheumatoid arthritis, resistant to methotrexate monotherapy.

Detailed Description

Stage 1: there are 3 dose levels and 5 cohorts. The subjects will be followed up for up to 71 days after the IP administration.

Stage 2: the main period of the study (Weeks 0-24) is blinded; study subjects will receive levilimab with placebo. At Week 24 the study will become open-label and all subjects will continue to receive levilimab. At week 28 patients who achieved the RA remission at week 24 will be switched to maintenance therapy of levilimab and will receive it through Week 52. Subjects who do not achieve remission at Week 24, will continue to receive levilimab from Week 28 to Week 52 inclusive corresponding to their treatment group.

Study Timeline

• Study Start: 2022-12-07
• Study First Submitted: 2023-02-02
• Status Verified: 2023-03
• Study First Submitted QC: 2023-03-23
• Last Update Submitted: 2023-03-23
• Study First Posted: 2023-04-05
• Last Update Posted: 2023-04-05
• Primary Completion: 2024-09
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 261

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LVL648 group	Levilimab	levilimab 648 mg IV Q4W plus placebo starting from Week 0.
LVL162 group	Levilimab	Levilimab 162 mg SC QW plus placebo starting from Week 0.
LVL324 group	Levilimab	Levilimab 324 mg SC Q2W plus placebo starting from Week 0.

Primary Outcome Measures

Name	Time	Method
Safety primary endpoint (Stage 1)	Up to day 71	To determine the safety profile of levilimab following its single subcutaneous or intravenous administration at ascending doses in healthy subjects.
Low disease activity (Stage 2)	Up to Week 24	Proportion of subjects with low activity of rheumatoid arthritis (DAS28-ESR \<3.2) at Week 24 of the study in each treatment group.

Secondary Outcome Measures

Name	Time	Method
PK endpoints (Stage 1)	Up to Week 52	CL
ACR response (Stage 2, main period)	Week 24, 52	Proportion of subjects who achieved ACR20, ACR50 and ACR70
RA remission (Stage 2, main period)	Up to Week 52	Proportion of subjects who achieved RA remission according to DAS28-CRP (\<2.6), DAS28-ESR (\<2.6), CDAI (≤2.8), SDAI (≤3.3), and ACR/EULAR 2011
Changes in RA indexes (Stage 2, main period)	Week 24, 52	Change in DAS28-CRP, DAS28-ESR, CDAI and SDAI from baseline
Low disease activity (Stage 2, main period)	Week 24, 52	Proportion of subjects with low rheumatoid arthritis activity according to DAS28-CRP (\<3.2), DAS28-ESR (\<3.2), CDAI (≤10), SDAI (≤11)
Moderate/good response according to the EULAR criteria (Stage 2)	Week 24, 52	Proportion of subjects with moderate and good response according to the EULAR criteria at Week 24 and 52 compared with baseline values.
Change in the serum C-reactive protein concentration (Stage 2)	Week 24, 52	Change in the serum C-reactive protein concentration from baseline
Change in ESR (Stage 2)	Week 24, 52	Change in ESR from baseline
Change in the quality of life measured with SF-36 (Stage 2)	Week 24, 52	Change in the quality of life according to the SF-36 questionnaire from baseline
Change in the quality of life measured with the EQ-5D-3L (Stage 2)	Week 24, 52	Change in the quality of life according to the EQ-5D-3L questionnaire from baseline
Change in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) score (Stage 2)	Week 24, 52	Change in the fatigue assessments according to the FACIT-F questionnaire from baseline
Change in functional activity (Stage 2)	Week 24, 52	Change in the functional activity according to the HAQ-DI questionnaire from baseline
X-Ray assessment (Stage 2)	Week 24, 52	Radiographic characterization of the affected joints at Week 24: change in mean modified total Sharp/van der Heijde score (mTSS).
Key Secondary PK endpoint (Stage 2)	Week 24	Ctrough geometric mean in each treatment group

Trial Locations

Locations (1)

X7 Clinical Research; 🇷🇺 Saint Petersburg, Russian Federation