A Phase III Study of the Efficacy and Safety of Olokizumab in Patients With Polymyalgia Rheumatica

An International, Multicenter, Randomized, Double-blind, Placebo-controlled Phase 3 Study of the Efficacy and Safety of Olokizumab in Patients With Polymyalgia Rheumatica

The primary objective of the study is to evaluate the efficacy of olokizumab (OKZ) 64 mg administered subcutaneously every 2 weeks compared with placebo in participants with polymyalgia rheumatica (PMR). The secondary objectives are to evaluate the steroid-sparing effect, inflammatory markers, safety, tolerability, immunogenicity, and pharmacokinetics of OKZ in participants with PMR compared with placebo. The exploratory objectives are to evaluate OKZ efficacy in selected participant subgroups, biomarkers of bone metabolism, pharmacodynamic parameters, glucocorticoid-related effects, and quality of life in participants with PMR compared with placebo

Study Overview

• Status: Active, not recruiting
• Conditions: Polymyalgia Rheumatica
• Intervention / Treatment: Drug: Placebo; Biological: Olokizumab

Detailed Description

This is a Phase 3, double-blind, placebo-controlled, parallel-group study. A total of 120 participants with active polymyalgia rheumatica are planned to be randomized in a 1:1 ratio to one of the following treatment arms:

• OKZ arm: subcutaneous injections of OKZ 64 mg every 2 weeks
• Placebo arm: subcutaneous placebo injections every 2 weeks

Participants may continue stable methotrexate or leflunomide therapy during the screening and treatment periods

The treatment period lasts 16 weeks, during which participants visit the study center every 2 weeks for safety assessments and evaluation of treatment response. Starting from Week 6 (Visit 4), in participants with PMR-AS <10, a gradual weekly glucocorticoid taper is initiated, decreasing by 2.5 mg/week until a dose of 5 mg/day is reached, followed by reductions of 1.25 mg/week until complete discontinuation of glucocorticoids. If complete discontinuation is not feasible at a dose of 5 mg/day or lower, tapering may be paused based on the investigator's clinical judgment

Participants who do not enter an open-label extension study after completion of the 16-week double-blind treatment period enter a 22-week safety follow-up (SFU) period. During follow-up, participants attend clinic visits at 2, 10, and 22 weeks after the end-of-treatment (EOT) visit for SFU assessments. The total duration of the study for participants is approximately 42 weeks

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russia
  • Izhevsk, Russia, 426009
    • Udmurt Republic Clinical and Diagnostic Center, Ministry of Health of the Udmurt Republic
  • Korolyov, Russia, 141060
    • Family Polyclinic No. 4 LLC
  • Moscow, Russia, 111123
    • A.S. Loginov Moscow Clinical Scientific Center
  • Moscow, Russia, 115522
    • V.A. Nasonova Research Institute of Rheumatology
  • Moscow, Russia, 119435
    • I.M. Sechenov First Moscow State Medical University, Center for Clinical Studies of Medicinal Products
  • Moscow, Russia, 129110
    • M.F. Vladimirsky Moscow Regional Research and Clinical Institute (MONIKI)
  • Moscow, Russia, 129226
    • Russian Gerontology Research and Clinical Center, Pirogov Russian National Research Medical University
  • Nizhny Novgorod, Russia, 603126
    • N.A. Semashko Nizhny Novgorod Regional Clinical Hospital
  • Novosibirsk, Russia, 630099
    • Healthy Family Medical Center LLC
  • Novosibirsk, Russia, 630117
    • Research Institute of Clinical and Experimental Lymphology - Branch of the Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
  • Omsk, Russia, 644012
    • Omsk Regional Clinical Hospital
  • Ryazan, Russia, 390026
    • Academician I.P. Pavlov Ryazan State Medical University
  • Saint Petersburg, Russia, 194214
    • Interleukin LLC
  • Saint Petersburg, Russia, 196066
    • Medical and Sanitary Unit No. 157 LLC
  • Smolensk, Russia, 214025
    • Smolensk Regional Rheumatology Center at the Clinical Hospital "RZD-Medicine" of the City of Smolensk (Private Healthcare Institution)
  • Tomsk, Russia, 634050
    • Siberian State Medical University, Ministry of Health of the Russian Federation
  • Ufa, Russia, 450005
    • State Budgetary Healthcare Institution Republican Clinical Hospital named after G.G. Kuvatov
  • Vladimir, Russia, 600005
    • Biomed LLC
  • Yaroslavl, Russia, 150047
    • Yaroslavl Central City Hospital
  • Yaroslavl, Russia, 150054
    • Center for Medical Consultations and Research - PRAKTIKA LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Presence of written informed consent (IC) signed by the participant
• Confirmed diagnosis of polymyalgia rheumatica (PMR) according to the 2012 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria

• At the time of randomization, participants must meet one of the following conditions:

  1. stable glucocorticoid (GC) therapy at a dose of ≤20 mg/day prednisone equivalent for at least 2 weeks; or
  2. no glucocorticoid (GC) therapy for at least 2 weeks

• PMR flare within 3 days prior to randomization meeting the following criteria:

  1. Polymyalgia Rheumatica Activity Score (PMR-AS) ≥10;
  2. C-reactive protein (CRP) level ≥5 mg/L in the absence of alternative causes of elevation

Exclusion Criteria:

• Presence of cranial symptoms of giant cell arteritis (GCA) within 12 weeks prior to screening
• Presence of concomitant fibromyalgia or neuropathic pain syndrome
• Presence of other systemic rheumatic diseases, including rheumatoid arthritis, Sjögren's syndrome, vasculitis (except GCA), dermatomyositis/polymyositis, and others
• Presence of concomitant conditions associated with chronic pain syndrome that could potentially interfere with efficacy assessments in the study
• Bilateral limitation of upper limb elevation above 90° (elevation of upper limbs [EUL] score 1) not related to active polymyalgia rheumatica (PMR)
• Requirement for systemic glucocorticoid (GC) therapy for conditions other than PMR
• Prior treatment with interleukin-6 (IL-6) inhibitors (including OKZ) or IL-6 receptor inhibitors, except when used for treatment of coronavirus disease 2019 (COVID-19). For participants treated with these agents for COVID-19, the last administration must have occurred at least 6 months prior to screening
• Intravenous, intra-articular, periarticular, or intramuscular glucocorticoid administration within 4 weeks prior to screening

• Use of the following medications prior to screening:

  1. Janus kinase (JAK) inhibitors (including tofacitinib, baricitinib, or upadacitinib) within 4 weeks;
  2. Tumor necrosis factor-alpha (TNF-α) inhibitors: etanercept within 2 weeks; adalimumab, golimumab, certolizumab, or infliximab within 8 weeks;
  3. Rituximab within 12 months prior to screening;
  4. Abatacept within 8 weeks prior to screening;
  5. Interleukin-1 (IL-1) inhibitors: canakinumab within 12 weeks; anakinra within 72 hours; goflikicept within 8 weeks;
  6. Interleukin-17 (IL-17), interleukin-23 (IL-23), or interleukin-12/23 (IL-12/23) inhibitors: secukinumab, bimekizumab, ustekinumab, tildrakizumab, risankizumab, mirikizumab, or netakimab within 16 weeks; ixekizumab, brodalumab, or guselkumab within 12 weeks;
  7. Other genetically engineered biologic therapies within at least 5 half-lives prior to screening;
  8. Alkylating agents, including cyclophosphamide, within 24 weeks;
  9. Cyclosporine, azathioprine, or mycophenolate mofetil within 4 weeks
• Initiation, discontinuation, or dose modification of methotrexate or leflunomide within 12 weeks prior to screening
• Modification of other PMR therapy within 4 weeks or 5 half-lives prior to screening, whichever is longer
• Administration of a live vaccine within 6 weeks prior to baseline assessment or planned live vaccination during the study
• Participation in another clinical study within 30 days prior to baseline assessment or within 5 half-lives of the investigational product used in that study, whichever is longer
• Previous participation in this study (participant randomized and received at least one dose of investigational product)
• Hematologic disorders, including platelet, leukocyte, or erythrocyte disorders (e.g., sickle cell anemia, myelodysplastic syndrome, hematologic malignancies, multiple myeloma, hemolytic anemia, or thalassemia) or coagulopathies
• Current malignancy or history of malignancy within the past 5 years, except adequately treated cervical carcinoma in situ, basal cell carcinoma, or squamous cell skin carcinoma treated at least 1 year prior to screening (with no more than 3 excised skin cancers within 5 years prior to screening)

• Screening laboratory abnormalities including:

  1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥1.5 × upper limit of normal (ULN);
  2. Platelet count <100 × 10^9/L (<100,000/mm^3);
  3. White blood cell count <3.5 × 10^9/L;
  4. Absolute neutrophil count <2,000 × 10^6/L (<2,000/mm^3)
• Positive human immunodeficiency virus (HIV) test at screening or history of HIV infection

• Screening evidence of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection:

  1. Participants previously treated for HCV infection with undetectable viral load for at least 6 months may be eligible with specialist approval;
  2. Participants positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (anti-HBc) are excluded;
  3. Participants with isolated positive hepatitis B surface antibody (anti-HBs) and prior vaccination history may be eligible
• History of active tuberculosis (TB); suspected or confirmed active TB; radiographic evidence of active pulmonary TB at screening; or TB risk factors including recent incarceration, homelessness, occupational exposure, or close contact with individuals with active TB within 1 year prior to randomization
• History of latent tuberculosis infection (LTBI) without adequate treatment regardless of QuantiFERON-TB/T-SPOT.TB results, or positive QuantiFERON-TB/T-SPOT.TB test at screening. Participants may be re-screened if active TB is excluded by a qualified specialist, at least 30 days of prophylactic therapy for LTBI have been completed, and the participant agrees to complete the recommended course of therapy

• Participants with the following cardiovascular diseases:

  1. Decompensated congestive heart failure or New York Heart Association (NYHA) Class III or IV heart failure;
  2. Resistant or uncontrolled hypertension requiring adjustment of antihypertensive therapy;
  3. Severe or uncontrolled cardiovascular disease, including acute coronary syndrome, stroke, or transient ischemic attack within 3 months prior to screening
• Any severe and/or uncontrolled concomitant disease (including uncontrolled severe hyperlipidemia, uncontrolled diabetes mellitus, respiratory, hepatic, renal, gastrointestinal, endocrine, dermatologic, neurologic, psychiatric, hematologic, immunologic, or immunodeficiency disorders) that, in the investigator's opinion, may interfere with study participation or interpretation of study results
• Acute infection at screening, exacerbation of chronic infection, infection requiring oral antimicrobial therapy within 4 weeks prior to screening, injectable antimicrobial therapy within 6 weeks prior to randomization, or severe/recurrent infections requiring hospitalization within 6 months prior to randomization
• History within 6 months prior to screening of disseminated herpes zoster infection, herpes zoster-associated encephalitis or meningitis, or other severe herpes zoster infections not resolving without treatment
• Any other clinically significant chronic infection (including invasive fungal infections or osteomyelitis) that, in the investigator's opinion, may increase the risk of infectious complications during the study
• Planned surgical intervention during the study, surgery within 4 weeks prior to screening (except minimally invasive diagnostic procedures), or incomplete recovery from surgery in the investigator's opinion
• History or presence of diverticulitis, ulcerative colitis, Crohn's disease, gastrointestinal perforation, or other gastrointestinal conditions associated with increased risk of perforation
• Alcohol or substance abuse in the investigator's opinion
• Pregnancy, breastfeeding, or planned pregnancy during the study or within 6 months after the last dose of investigational treatment
• Women of childbearing potential unwilling to use highly effective contraception during the study and for 6 months after the last dose of investigational product, or men with partners of childbearing potential unwilling to use highly effective contraception during the study and for at least 3 months after the last dose of investigational product
• Known hypersensitivity to OKZ, any component of the investigational product, or placebo
• History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
• Unwillingness or inability to comply with study procedures required by the protocol
• Any medical, psychiatric, or laboratory abnormality that, in the investigator's opinion, may increase the risk associated with study participation or interfere with interpretation of study results, making the participant unsuitable for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Olokizumab; Olokizumab 64 mg every 2 weeks, administered as a single 0.4 mL subcutaneous injection	Biological: Olokizumab; Solution for subcutaneous injection in a prefilled syringe (1 mL) with a concentration of 160 mg/mL, administered as a 64 mg/0.4 mL dose; Other Names: Artlegia
Placebo Comparator: Placebo; Placebo every 2 weeks, administered as a single 0.4 mL subcutaneous injection	Drug: Placebo; 0.9% Sodium Chloride solution for Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of treatment response	Treatment response is defined as Polymyalgia Rheumatica Activity Score (PMR-AS) <10 and glucocorticoid (GC) dose ≤5 mg/day, or a reduction of ≥10 mg/day, or no new initiation of GC therapy (in participants not receiving GC at baseline), up to Week 16	Up to Week 16 (visit 9)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with Polymyalgia Rheumatica Activity Score (PMR-AS) <7 at each visit	PMR-AS index is calculated (to two decimal places) as the sum of five variables: duration of morning stiffness in minutes (MST, morning stiffness), multiplied by 0.1; elevation of the upper limbs (EUL, scored from 0 to 3); physician global assessment of disease activity using a 10-point visual analogue scale (VASphys); patient-reported pain intensity using a 10-point visual analogue scale (VASpain); and C-reactive protein (CRP) level (mg/dL)	Up to Week 16 (visit 9)
Proportion of participants with Polymyalgia Rheumatica Activity Score (PMR-AS) <10 at each visit	PMR-AS index is calculated (to two decimal places) as the sum of five variables: duration of morning stiffness in minutes (MST, morning stiffness), multiplied by 0.1; elevation of the upper limbs (EUL, scored from 0 to 3); physician global assessment of disease activity using a 10-point visual analogue scale (VASphys); patient-reported pain intensity using a 10-point visual analogue scale (VASpain); and C-reactive protein (CRP) level (mg/dL)	Up to Week 16 (visit 9)
Change in Polymyalgia Rheumatica Activity Score (PMR-AS) over the treatment period compared with baseline	PMR-AS index is calculated (to two decimal places) as the sum of five variables: duration of morning stiffness in minutes (MST, morning stiffness), multiplied by 0.1; elevation of the upper limbs (EUL, scored from 0 to 3); physician global assessment of disease activity using a 10-point visual analogue scale (VASphys); patient-reported pain intensity using a 10-point visual analogue scale (VASpain); and C-reactive protein (CRP) level (mg/dL)	Baseline and Week 16 (visit 9)
Change from baseline in pain assessed using a visual analogue scale (VASpain)	Change from baseline in pain assessed by the patient using a visual analogue scale (VASpain). VASpain range: 0 to 10; where 0= no activity and 10= maximum activity	Baseline and Week 16 (visit 9)
Change from baseline in duration of morning stiffness	Change from baseline in duration of morning stiffness measured in minutes	Baseline and Week 16 (visit 9)
Change from baseline in upper limb elevation score	Change from baseline in upper limb elevation assessed on a 0-3 scale. Higher scores indicate worse outcome	Baseline and Week 16 (visit 9)
Change from baseline in investigator-assessed disease activity	Change from baseline in disease activity assessed by the investigator using a visual analogue scale (VASphys). VASphys range: 0 to 10; where 0= no activity and 10= maximum activity	Baseline and Week 16 (visit 9)
Proportion of participants with new initiation or dose increase of glucocorticoids	Proportion of participants with new initiation of glucocorticoid (GC) therapy or an increase in GC dose compared with baseline	Baseline and Week 16 (visit 9)
Change in proportion of participants receiving glucocorticoids over time	Change from baseline in the proportion of participants receiving glucocorticoids (GC), overall and in subgroups of participants receiving or not receiving GC at baseline	Baseline and Week 16 (visit 9)
Change from baseline in mean glucocorticoid dose	Change from baseline in mean daily glucocorticoid dose in each treatment arm	Baseline and Week 16 (visit 9)
Cumulative glucocorticoid dose	Total cumulative glucocorticoid dose during the treatment period	Baseline and Week 16 (visit 9)
Change from baseline in C-reactive protein (CRP) levels	Change from baseline in serum C-reactive protein (CRP) levels during the treatment period	Baseline and Week 16 (visit 9)
Change from baseline in erythrocyte sedimentation rate (ESR)	Change from baseline in erythrocyte sedimentation rate (ESR) during the treatment period	Baseline and Week 16 (visit 9)
Change from baseline in patient global assessment of disease activity	Physician global assessment of disease activity (VAS range: 0 to 10; where 0= no activity and 10= maximum activity). Higher scores indicate better outcome	Baseline and Week 16 (visit 9)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Polymyalgia Rheumatica Activity Score (PMR-AS) in subgroups of participants receiving or not receiving glucocorticoids at baseline	Change from baseline in Polymyalgia Rheumatica Activity Score (PMR-AS) in subgroups of participants receiving or not receiving glucocorticoids at baseline	Baseline and Week 16 (visit 9)
Change from baseline in interleukin-6 (IL-6) levels	Change from baseline in serum interleukin-6 (IL-6) levels during the treatment period	Baseline and Week 16 (visit 9)
Change from baseline in soluble interleukin-6 (IL-6) receptor levels	Change from baseline in soluble interleukin-6 receptor levels during the treatment period	Baseline and Week 16 (visit 9)
Change from baseline in matrix metalloproteinase-3 (MMP-3) levels	Change from baseline in serum matrix metalloproteinase-3 (MMP-3) levels during the treatment period	Baseline and Week 16 (visit 9)
Change from baseline in serum ferritin levels	Change from baseline in serum ferritin levels during the treatment period	Baseline and Week 16 (visit 9)
Change from baseline in bone metabolism biomarkers	Bone metabolism biomarkers include bone-specific alkaline phosphatase, osteocalcin, procollagen type I N-terminal propeptide (P1NP), and C-terminal telopeptide of type I collagen (β-CrossLaps) during the treatment period	Baseline and Week 16 (visit 9)
Change from baseline in SF-36v1 score	Change from baseline in SF-36 version 1 health survey scores during the treatment period	Baseline and Week 16 (visit 9)
Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT) score	Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT) score during the treatment period	Baseline and Week 16 (visit 9)
Change in glucocorticoid-related toxicity parameters	Change in parameters characterizing glucocorticoid-related toxicity during the treatment period	Baseline and Week 16 (visit 9)
Proportion of participants with cranial symptoms of giant cell arteritis	Proportion of participants with cranial symptoms of giant cell arteritis during the treatment period	Baseline and Week 16 (visit 9)
Mean plasma trough concentrations (Ctrough) of olokizumab (OKZ)	Mean plasma trough concentrations (Ctrough) of olokizumab (OKZ) in participants with Polymyalgia Rheumatica (PMR) prior to dosing during the treatment period	Pre-dose at each visit up to Week 16 (visit 9) and at Week 26
Time to steady-state concentration of olokizumab (OKZ)	Time to steady-state concentration of olokizumab (OKZ)	Pre-dose at each visit up to Week 16 (visit 9) and at Week 26
Proportion of participants with laboratory abnormalities	Laboratory assessments include: Blood test for inflammatory markers (C-reactive protein, Erythrocyte Sedimentation Rate, ferritin); Blood test for bone metabolism markers (bone-specific alkaline phosphatase (bone ALP), osteocalcin, procollagen type I N-terminal propeptide (P1NP), C-terminal telopeptide of type I collagen (β-CrossLaps), matrix metalloproteinase-3 (MMP-3)); Blood test for cytokine levels (IL-6, IL-6R)	Baseline and Week 38
Proportion of participants with vital sign abnormalities	Vital signs include systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, body temperature	Baseline and Week 38
Proportion of participants with physical examination abnormalities	Physical examination includes skin, heart, lungs, abdomen, liver, spleen, ENT organs, lymph nodes	Baseline and Week 38
Incidence of anti-drug antibodies (ADA) to olokizumab (OKZ)	Incidence of anti-drug antibodies (ADA) to olokizumab (OKZ)	Up to Week 26
Incidence of neutralizing antibodies (nAb) to olokizumab (OKZ)	Incidence of neutralizing antibodies (nAb) to olokizumab (OKZ)	Up to Week 26
Titers of anti-drug antibodies (ADA) to olokizumab (OKZ)	Titers of anti-drug antibodies (ADA) to olokizumab (OKZ)	Up to Week 26
Duration of neutralizing antibody (nAb) persistence	Duration of neutralizing antibody (nAb) persistence	Up to Week 26
Proportion of participants discontinuing treatment due to adverse events	Safety assessments are conducted from first dose through safety follow-up 3 (SFU3). The end-of-study follow-up includes three SFU visits (SFU1-SFU3). Timing of SFU1 varies depending on treatment completion status: SFU1 occurs at the end-of-treatment (EOT) visit for participants completing the protocol treatment period, or approximately 14 days after early treatment discontinuation. SFU2 and SFU3 occur at approximately 70 and 154 days after EOT visit, respectively	Up to Week 38
Character, frequency, severity and outcome of adverse events (AEs), including serious adverse events (SAEs)	Safety assessments are conducted from first dose through safety follow-up 3 (SFU3). The end-of-study follow-up includes three SFU visits (SFU1-SFU3). Timing of SFU1 varies depending on treatment completion status: SFU1 occurs at the end-of-treatment (EOT) visit for participants completing the protocol treatment period, or approximately 14 days after early treatment discontinuation. SFU2 and SFU3 occur at approximately 70 and 154 days after EOT visit, respectively Adverse event severity is graded 1-5 (mild, moderate, severe, life-threatening, death) per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0	Up to Week 38

Collaborators and Investigators

• Sponsor: R-Pharm International, LLC
• Investigators: Study Director: Mikhail Samsonov, R-Pharm

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2025
• Primary Completion (Actual): April 10, 2026
• Study Completion (Estimated): July 9, 2026

Study Registration Dates

• First Submitted: June 19, 2026
• First Submitted That Met QC Criteria: June 19, 2026
• First Posted (Actual): June 26, 2026

Study Record Updates

• Last Update Posted (Actual): June 26, 2026
• Last Update Submitted That Met QC Criteria: June 19, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Polymyalgia Rheumatica; Olokizumab; Artlegia
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Muscular Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Polymyalgia Rheumatica; olokizumab
• Other Study ID Numbers: CL04041376

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No