Safety, Tolerability and Efficacy of GcMAF in Patients With Chronic Inflammatory Diseases

This trial is designed to evaluate GcMAF, an immunomodulatory protein generated from vitamin D-binding protein (DBP) via specific enzymatic deglycosylation, in adults (≥18 years) with a confirmed chronic inflammatory disease (e.g., moderate rheumatoid arthritis, chronic cystitis) who have experienced inadequate response or intolerance to standard anti-inflammatory treatments (NSAIDs, corticosteroids, etc.). GcMAF's primary mechanism of action involves activating macrophages and dendritic cells, regulating cytokine production, and potentially offering anti-inflammatory as well as antitumor benefits, as indicated in preclinical studies on animal models with conditions such as adjuvant arthritis and hemorrhagic cystitis.

The study will be conducted in two phases. Phase I is an open-label, dose-escalation investigation comprising 3-4 cohorts receiving increasing doses of GcMAF (administered subcutaneously or intramuscularly). The primary objectives for Phase I are to determine the safety profile, tolerability, and maximum tolerated dose (MTD) or Recommended Dose (RD). This will involve continuous safety monitoring, assessment of adverse events (AEs) using CTCAE criteria, and evaluation of lab parameters (hematology, biochemistry, inflammatory markers). Secondary endpoints in Phase I include preliminary efficacy measures (changes in CRP, ESR, cytokines, and disease-activity scores) and (Cmax, Tmax, AUC, T½), along with possible measurement of antibodies to GcMAF.

Upon establishing the RD in Phase I, Phase II will be a randomized, double-blind, placebo-controlled trial enrolling approximately 60-120 patients. They will be allocated (1:1 or 1:1:1 if multiple GcMAF doses are tested) to receive either GcMAF (RD) or placebo for 12-16 weeks, followed by a 4-8-week observation period. The key inclusion criteria stipulate adult patients with documented chronic inflammatory disease and the ability to adhere to the protocol. Exclusion criteria include pregnancy or lactation, severe systemic illnesses (e.g., liver/kidney failure), active serious infections (HIV, TB, or active hepatitis B/C), recent participation in other experimental studies (<3 months), and hypersensitivity to protein products.

Phase II primary endpoints focus on clinical efficacy, measured by validated scores (e.g., DAS28 for rheumatoid arthritis, symptom indices for cystitis) and the proportion of patients achieving clinically significant improvement (e.g., DAS28 improvement ≥1.2 points). Secondary endpoints include ongoing safety assessments, laboratory markers of inflammation (CRP, ESR, cytokine profile), pharmacodynamic data (such as M1/M2 macrophage ratio), and patient-reported outcomes (e.g., SF-36, HAQ-DI). Statistical analyses will include descriptive methods in Phase I for safety and tolerability, and for Phase II comparative tests (t-test, ANOVA, or nonparametric equivalents) for continuous data and chi-square or Fisher's exact test for categorical response rates. Ultimately this trial seeks to confirm whether GcMAF offers a clinically meaningful reduction of inflammatory disease activity while maintaining an acceptable safety profile.

Inclusion criteria

• Inclusion criteria
• Age ≥ 18 years, informed consent.
• Confirmed diagnosis of a chronic inflammatory disease (e.g., moderate rheumatoid arthritis or chronic cystitis, or another validated nosology) according to recognized criteria.
• Insufficient effect or intolerance of standard anti-inflammatory therapy (NSAIDs, GCS, etc.).
• Ability to comply with the study protocol.

Exclusion criteria

• Pregnancy, lactation (lack of safety data in this group).
• Severe systemic diseases (liver/renal failure, severe cardiovascular diseases, uncontrolled arterial hypertension).
• Active serious infections (HIV, tuberculosis, hepatitis B/C in the active phase).
• Previous participation in other experimental studies < 3 months ago.
• Severe allergy to protein components of the drug.