A Phase 1b Study of Imvotamab in Moderate to Severe Rheumatoid Arthritis

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and tolerability of imvotamab in patients with moderate to severe rheumatoid arthritis who have failed prior therapies. Participants will be given imvotamab or placebo through a vein (i.e., intravenously). A placebo is a look-alike substance that contains no active drug

Detailed Description
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This is a Phase 1b, randomized, placebo-controlled, multicenter study to determine the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of imvotamab in adult participants with active RA who are refractory or intolerant to 2 previous biologic disease-modifying anti-rheumatic drugs (bDMARD) or targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARD) therapies. Approximately 24 participants will be sequentially assigned to different dose escalation cohorts.

Official Title
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A Phase 1b, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Imvotamab in Participants With Moderate to Severe Rheumatoid Arthritis Who Have Failed Prior Therapies

Conditions
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Rheumatoid Arthritis, Arthritis, Rheumatoid, Arthritis

Intervention / Treatment
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* Drug: Imvotamab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Age ≥ 18 years at the time of signing ICF Documented diagnosis of RA and meeting the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA at least 1 year prior to screening Have had treatment with bDMARDs and/or tsDMARD and were refractory by 1 of 2 reasons: Lack of benefit to at least 2 bDMARDs in different mechanism classes or 1 bDMARD and 1 tsDMARD, after at least 12 weeks of treatment, in the opinion of the investigator. Lack of benefit may include inadequate improvement in joint counts, physical function, or disease activity. Intolerance to at least 2 bDMARDs in different mechanism classes or 1 bDMARD and 1 tsDMARD. Minimum of 6 swollen (SJC) and 6 tender joints (TJC) on a 66/68 joint count at the screening and baseline visit (SJC/TJC) Central lab results for hsCRP ≥ 0.8 mg/dL Anti-citrullinated protein antibodies (ACPA) positive and/or rheumatoid factor (RF) positive If using oral corticosteroids (OCS), must be on a stable dose equivalent to ≤ 10 mg/day of prednisone for at least 2 weeks prior to first study treatment Key Exclusion Criteria: History of a rheumatologic autoimmune disease other than RA (except secondary Sjögren's syndrome), or with significant systemic involvement secondary to RA (vasculitis, pulmonary fibrosis, or Felty's syndrome); Juvenile idiopathic arthritis (JIA) or idiopathic arthritis diagnosed before the age of 16 years; Psoriatic Arthritis; Axial spondylarthritis or any other disease associated with inflammatory arthritis; Active fibromyalgia with pain symptoms or signs that would interfere with clinical assessments for RA Receipt of an investigational therapy less than 3 months or 5 drug-elimination half-lives (whichever is longer) prior to first administration of study treatment and during the study Receipt of any of the following excluded RA therapies: Any cell depleting therapy, anti-CD4, anti-CD5, anti-CD3, rituximab, ocrelizumab, or ofatumumab, less than 6 months prior to first administration of study treatment. Have received prior tsDMARds including but not limited to inhibitors of Janus kinase (JAK), Bruton tyrosine kinase, or tyrosine kinase 2, including baricitinib, tofacitinib, upadacitinib, filgotinib, ibrutinib, or fenebrutinib, or any investigational agent less than 3 months or 5 half-lives, whichever is longer, prior to first administration of study treatment Have received prior immunomodulatory bDMARDs for RA including, but not limited to adalimumab, golimumab, ustekinumab, secukinumab, tocilizumab, abatacept, or other inhibitors of TNF, IL-6, IL-23, or IL-17 less than 3 months or 5 half-lives, whichever is longer, prior to first administration of the study treatment Requiring therapy with prednisone > 10 mg/day (or equivalent dose) within 2 weeks prior to first study treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imvotamab (Dose Escalation)<br>Imvotatmab administered intravenously | Drug: Imvotamab<br>* Administered intravenously<br>|
| Placebo Comparator: PBO IV QW x 4 doses<br>Placebo administered intravenously | Drug: Placebo<br>* 0.9% sodium chloride administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of imvotamab | Incidence of adverse events (AEs), serious adverse events (SAEs), including serious infectious events (SIEs) and opportunistic infections (OIs) | Up to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bDMARD, Arthritis, Moderate to severe arthritis, active rheumatoid arthritis, tsDMARD, refractory