EF-M2 (Immutalon) Multiple Ascending Dose Study in Moderate-to-Severe Rheumatoid Arthritis

NCT07349420 | Completed Phase 1

• 1 other identifier: SW032
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This is a first-in-human, open-label, phase I/IIa, multiple ascending dose study of EF-M2 (Immutalon), a macrophage-modulating investigational product intended to shift macrophages toward an anti-inflammatory (M2-like) phenotype via a CLEC10A-mediated mechanism. The study will enroll adults with moderate-to-severe rheumatoid arthritis. Participants will receive EF-M2 as subcutaneous injections for 4 weeks in sequential dose cohorts (1, 3, 5, or 7 mcg administered twice weekly; optional expanded pharmacodynamic cohorts may receive 3 or 5 mcg three times weekly). The total number of injections will be 8-12 depending on the regimen. Dose escalation is sequential and overseen by an independent data safety monitoring board (DSMB), with sentinel dosing at the start of each new cohort. Participants may be followed off drug for up to 8-12 weeks after treatment, for a total participation time of up to 16 weeks (including screening). The primary objective is to evaluate safety, tolerability, and immunogenicity. Secondary objectives include assessing pharmacodynamic markers of M2 polarization (e.g., changes in ARG1/iNOS and IL-10/TNF-α ratios and M2-associated cell phenotypes) and exploring associations with clinical activity measures.

Conditions

Rheumatoid Arthritis

Keywords

EF-M2; Immutalon; Multiple Ascending Dose; Macrophage Repolarization

Outcome Measures

Primary Outcomes (4)

• Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events

  Number and percentage of participants with any treatment-emergent adverse event and with any serious adverse event during the study. Events will be coded and summarized by severity and relationship to study drug; severity will be graded using the Common Terminology Criteria for Adverse Events. Range and Units: Count: 0 to total number of participants. Percentage: 0% to 100%.

  From first dose (Day 0) through end of follow-up (Day 112)

• Incidence of Dose-Limiting Toxicities

  Number and percentage of participants who experience a dose-limiting toxicity during the dose-limiting toxicity evaluation period (pre-defined clinically significant toxicities, including severe toxicities graded using the Common Terminology Criteria for Adverse Events, immune complications, and severe infections as specified by protocol). Range and Units: Count: 0 to total number of participants in the cohort. Percentage: 0% to 100%.

  From first dose (Day 0) through end of dosing period (Day 28)

• Percentage of Participants With Treatment-Emergent Clinically Significant Laboratory Abnormalitie

  Treatment-emergent clinically significant laboratory abnormality is defined as a post-baseline abnormality meeting Grade 3 or Grade 4 severity criteria (per CTCAE v5.0, or equivalent protocol-defined grading) in any of the assessed laboratory parameters, including hematology (CBC with differential and platelets), serum chemistry (ALT, AST, alkaline phosphatase, bilirubin, creatinine, urea, electrolytes), inflammatory markers (C-reactive protein, fibrinogen), and immune markers (immunoglobulins and complement). A participant will be counted once if they experience ≥1 qualifying abnormality at any post-baseline assessment. Results will be summarized as a percentage of participants.

  Baseline (Day 0) and Days 7, 14, 28, 56, 84, and 112

• Proportion of Participants With Anti-Drug Antibodies and Neutralizing Antibodies to EF-M2

  Number and percentage of participants with a positive anti-drug antibody result to EF-M2 in serum. Neutralizing antibodies will be assessed in participants with positive anti-drug antibodies. Range and Units: Count: 0 to total number of participants tested. Percentage: 0% to 100%.

  Baseline (Day 0) and Days 28, 56, 84, and 112

Secondary Outcomes (5)

• Change From Baseline in Arginase 1 to Inducible Nitric Oxide Synthase Ratio

  Baseline (Day 0) to Day 28, Day 56, and Day 84

• Change From Baseline in Plasma Interleukin 10 to Tumor Necrosis Factor Alpha Ratio

  (Day 0) to Day 28, Day 56, and Day 84

• Change From Baseline in Proportion of Monocytes With M2-Associated Phenotype

  Baseline (Day 0) to Day 28, Day 56, and Day 84

• Pharmacodynamic Differences Between Dose Levels and Dosing Regimens

  Baseline (Day 0) to Day 28, Day 56, and Day 84

• Dose-Pharmacodynamic Relationship for M2 Polarization Markers

  Baseline (Day 0) to Day 28, Day 56, and Day 84

Study Arms (6)

Cohort 1: EF-M2 1 mcg SC Twice Weekly

EXPERIMENTAL

Participants receive EF-M2 (Immutalon) 1 mcg by subcutaneous injection twice weekly for 4 weeks (8 injections total).

Drug: EF-M2

Cohort 2: EF-M2 3 mcg SC Twice Weekly

EXPERIMENTAL

Participants receive EF-M2 (Immutalon) 5 mcg by subcutaneous injection twice weekly for 4 weeks (8 injections total).

Drug: EF-M2

Cohort 4: EF-M2 7 mcg SC Twice Weekly

EXPERIMENTAL

Participants receive EF-M2 (Immutalon) 7 mcg by subcutaneous injection twice weekly for 4 weeks (8 injections total).

Drug: EF-M2

Cohort 5: EF-M2 3 mcg SC Three Times Weekly

EXPERIMENTAL

Participants receive EF-M2 (Immutalon) 3 mcg by subcutaneous injection three times weekly for 4 weeks (12 injections total). Optional expanded pharmacodynamic cohort.

Drug: EF-M2

Cohort 6: EF-M2 5 mcg SC Three Times Weekly

EXPERIMENTAL

Participants receive EF-M2 (Immutalon) 5 mcg by subcutaneous injection three times weekly for 4 weeks (12 injections total). Optional expanded pharmacodynamic cohort.

Drug: EF-M2

Cohort 3: EF-M2 5 mcg SC Twice Weekly

EXPERIMENTAL

Participants receive EF-M2 (Immutalon) 5 mcg by subcutaneous injection twice weekly for 4 weeks (8 injections total).

Drug: EF-M2

Interventions

EF-M2 DRUG

EF-M2 (Immutalon) is an investigational product administered as a subcutaneous injection. In this study, participants receive EF-M2 for 4 weeks in sequential multiple ascending dose cohorts: 1, 3, 5, or 7 mcg twice weekly (8 injections total). Optional expanded pharmacodynamic cohorts may receive 3 or 5 mcg three times weekly (12 injections total).

Cohort 1: EF-M2 1 mcg SC Twice Weekly; Cohort 2: EF-M2 3 mcg SC Twice Weekly; Cohort 3: EF-M2 5 mcg SC Twice Weekly; Cohort 4: EF-M2 7 mcg SC Twice Weekly; Cohort 5: EF-M2 3 mcg SC Three Times Weekly; Cohort 6: EF-M2 5 mcg SC Three Times Weekly

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 70 years.
• Diagnosis of rheumatoid arthritis according to the 2010 American College of - Rheumatology and European Alliance of Associations for Rheumatology classification criteria for at least 6 months.
• Moderate-to-severe active disease, defined as:
• Disease Activity Score in 28 joints using C-reactive protein at least 3.2 and not more than 6.0; and
• At least 6 tender joints and at least 6 swollen joints based on the 28-joint count.
• Inadequate response to at least one conventional synthetic disease-modifying antirheumatic drug (for example, methotrexate or leflunomide); and either:
• No prior biologic or targeted synthetic disease-modifying antirheumatic drug therapy; or
• No more than one prior line of biologic or targeted synthetic disease-modifying antirheumatic drug therapy, discontinued at least 12 weeks before screening.
• Stable background therapy:
• Conventional synthetic disease-modifying antirheumatic drug at a stable dose for at least 8 weeks; and
• Glucocorticoids at a dose not exceeding 10 milligrams per day of prednisone (or equivalent) at a stable dose for at least 4 weeks; and
• Nonsteroidal anti-inflammatory drugs and/or analgesics on a stable regimen for at least 2 weeks.
• Willingness and ability to comply with study visits, biospecimen collection, and contraception requirements (for women and men).

You may not qualify if:

• Current severe infection; active or latent tuberculosis without completed preventive therapy.
• Chronic hepatitis B, chronic hepatitis C, or human immunodeficiency virus infection with high viral load.
• Active malignancy or history of malignancy within 5 years, except adequately treated carcinoma in situ of the cervix or skin.
• History of severe opportunistic infections.
• Uncontrolled cardiovascular disease (including New York Heart Association class III or IV heart failure, acute coronary syndrome within the past 6 months, or uncontrolled arterial hypertension), decompensated diabetes mellitus, or severe liver or kidney disease.
• Pregnancy, breastfeeding, or planning pregnancy within 6 months.
• Prior treatment with cellular therapies, chimeric antigen receptor T-cell therapy, or profound immunosuppressive therapies with incomplete immune reconstitution.
• Any condition that, in the investigator's opinion, increases the risk of study participation.

Sponsors & Collaborators

• S.LAB (SOLOWAYS): lead
• Activator MAF, LLC: collaborator
• Center for New Medical Technologies, Novosibirsk, Russia: collaborator

Study Sites (1)

Center for New Medical Technologies

Novosibirsk, Novosibirsk Oblast, 630090, Russia

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label, multiple ascending dose study with sequential cohort dose escalation. Participants receive EF-M2 (Immutalon) by subcutaneous injection for 4 weeks (twice weekly in Cohorts 1-4). Optional expanded pharmacodynamic cohorts may evaluate increased dosing frequency (three times weekly). Sentinel dosing is used at the start of each new cohort, and dose escalation proceeds after DSMB review of safety and pharmacodynamic data.

Study Record Dates

• First Submitted: December 22, 2025
• First Posted: January 16, 2026
• Study Start: June 3, 2025
• Primary Completion: October 5, 2025
• Study Completion: December 6, 2025
• Last Updated: January 16, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)