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Safety, Tolerability, Pharmacodynamics and Efficacy Study of TAB08 in Patients With Rheumatoid Arthritis

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ClinicalTrials.gov Identifier: NCT01990157
Recruitment Status : Completed
First Posted : November 21, 2013
Last Update Posted : February 28, 2017
Sponsor:
Information provided by (Responsible Party):
Theramab LLC

Brief Summary:

This study is in two stages:

Stage 1 purpose is to assess safety, tolerability, and efficacy of multiple TAB08 doses in patients with active Rheumatoid Arthritis in which methotrexate (MTX) treatment is not enough effective.

Stage 2 purpose is to assess efficacy parameters (ACR criteria) of at least one selected TAB08 dose in extended patient population with active Rheumatoid Arthritis in which methotrexate (MTX) treatment with at least 10 mg/week is not enough effective.


Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: TAB08 Phase 1 Phase 2

Detailed Description:

Stage 1 is designed as standard phase 1 study with one arm and sequential dose cohorts with ascending doses. Each patient in each dose cohort will be administered TAB08 several times. After last TAB08 administration each patient will undergo investigational-treatment-free follow-up period.

At Stage 2 at least one TAB08 dose, selected during Stage 1 will be studied during longer timeframe in extended patient population.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety, Tolerability, Pharmacodynamics and Efficacy Study of TAB08 in Patients With Rheumatoid Arthritis in Which Methotrexate (MTX) Treatment is Not Effective
Actual Study Start Date : November 2013
Actual Primary Completion Date : December 2015
Actual Study Completion Date : February 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TAB08
Multiple TAB08 administrations as intravenous infusions.
Drug: TAB08
Weekly intravenous administration in escalating doses.
Other Name: Theralizumab




Primary Outcome Measures :
  1. Incidence of dose-limiting toxicity in every dose cohort [ Time Frame: From study drug infusion (Day 1) untill week 2 (Day 15) for each patient ]

Secondary Outcome Measures :
  1. Number of adverse events [ Time Frame: From study drug infusion (Day 1) untill the end of study stage 1 (Day 85) ]

Other Outcome Measures:
  1. Pharmacokinetics parameters of TAB08 after single and multiple i.v. administrations [ Time Frame: From study drug infusion (Day 1) untill Week 4 (Day 29) ]

    Following specific pharmacokinetics parameters will be used:

    C max - maximal concentration, AUC(0-t) - area under the curve concentration-time until the last time point of concentration measurement, AUC(0-∞) - area under the curve concentration-time extrapolated to infinity, T1/2 - final elimination half-life, Lambda z - elimination rate constant, CL - clearance, Vss - volume of distribution in steady state, C trough - trough concentration after multiple administration.


  2. Proportion of patients with American College of Rheumatology (ACR) 20 (50, 70) response criteria after 4 weeks of TAB08 treatment [ Time Frame: From study drug infusion (Day 1) untill the Week 4 (Day 29) ]
  3. Proportion of patients with ACR20 (50, 70) response criteria after 4 weeks of TAB08 treatment at the end of study stage 1 [ Time Frame: From study drug infusion (Day 1) untill tenf of study stage 1 (Day 85) ]


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must sign and date informed consent prior to any study procedures.
  2. Male and female patients aged 18-65 years.
  3. Rheumatoid arthritis (RA) diagnosed from 6 months to 10 years ago in accordance with American College of Rheumatology (ACR) diagnostic criteria of rheumatoid arthritis, 1987, or ACR / European League against Rheumatism (EULAR), 2010.
  4. Patients for whom standard treatment does not result in sufficient control of symptoms of RA, per investigator opinion.
  5. Treatment with Methotrexate for at least 3 months before Screening visit, and a stable dose of ≥ 10 mg weekly for at least 28 days before the first infusion of the study drug. Patients should be also treated with folic acid.
  6. Active disease of RA despite standard treatment:

    1. At least 6 out of 66 joints are swollen and at least 6 out of 68 joints are painful.
    2. Level of C-reactive protein >= 15 mg/L or erythrocyte sedimentation rate >= 28 mm/hour or morning stiffness > 45 minutes.
  7. Rheumatoid factor > 20 IU/mL.
  8. Adequate hematological, renal and hepatic laboratory values.
  9. For men and women of childbearing potential: consent to use double barrier methods of contraception during the entire study period.

Exclusion Criteria:

  1. Use of other disease-modifying antirheumatic drugs (DMARDs) except for Methotrexate within 4 weeks before the treatment initiation. Use of Leflunomide within 8 weeks before the first study drug infusion. Use of biological immunosuppressive drugs (Adalimumab, Etanercept, Infliximab, Anakinra, Abatacept and others) 2 months before the first study drug administration. Use of Rituximab within 12 months before the first study drug administration.
  2. Change of Methotrexate dose within 4 weeks before study treatment initiation.
  3. Any autoimmune disease except for rheumatoid arthritis and dry keratoconjunctivitis.
  4. Functional grade IV based on American College of Rheumatology scale.
  5. Active rheumatoid vasculitis.
  6. Any systemic diseases related to joint inflammation.
  7. Pregnant and breastfeeding women.
  8. Women with childbearing potential refusing to use effective contraceptive methods during the entire study period.
  9. Any active infectious disease or tuberculosis at the moment or within 2 weeks before inclusion into the study.
  10. Syphilis, hepatitis В, С, HIV-infection or tuberculosis based on the results of laboratory tests at Screening visit.
  11. Vaccination with live or attenuated vaccines within 6 weeks before the first study drug administration; planned vaccination during the study period.
  12. Medical history of recurrent clinically significant infections.
  13. Primary or secondary immunodeficiency.
  14. Medical history of malignant oncologic diseases except for excised basal cell skin cancer.
  15. Treatment with glucocorticosteroids (GKS) in a dose corresponding to over 12.5 mg/day of prednisolone equivalent, or change of GKS dose as well as treatment with intraarticular, i/m or i/v injections of GKS within 4 weeks before the first infusion of the study drug except for topical low active GKS, GKS in eardrops or eyedrops/ointment, inhalant GKS in a stable dose for the entire study period.
  16. Dose change of non-steroid anti-inflammatory agents within 4 weeks before first infusion of the study drug.
  17. Any factors that per investigator opinion might prevent patient from adhering to the visit schedule or performing study requirements.
  18. Participation in any other clinical study of an experimental drug within 3 months or within 5 elimination half-lives (depending on whichever is longer) before the first infusion of the study drug.
  19. Medical history of the following diseases: myocardial infarction, angina pectoris, bronchial asthma, chronic obstructive pulmonary disease or other cardiovascular or respiratory pathology which is considered serious by investigator.
  20. Current uncontrolled pathology of renal, endocrine, hematology or central nervous system.
  21. Alcohol and/or drug abuse within 1 year before first study drug administration.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01990157


Locations
Russian Federation
State Scientific and Research Rheumatology Institute
Moscow, Russian Federation, 115522
Clinical Emergency Hospital of Yaroslavl
Yaroslavl, Russian Federation, 150003
Sponsors and Collaborators
Theramab LLC
Investigators
Study Director: Daniil G Nemenov, M.D. Theramab LLC

Responsible Party: Theramab LLC
ClinicalTrials.gov Identifier: NCT01990157     History of Changes
Other Study ID Numbers: TAB08_RA01
First Posted: November 21, 2013    Key Record Dates
Last Update Posted: February 28, 2017
Last Verified: February 2017

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases