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

NCT01990157 | Completed Phase 1

• 1 other identifier: TAB08_RA01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Incidence of dose-limiting toxicity in every dose cohort

  From study drug infusion (Day 1) untill week 2 (Day 15) for each patient

Secondary Outcomes (1)

• Number of adverse events

  From study drug infusion (Day 1) untill the end of study stage 1 (Day 85)

Other Outcomes (3)

• Pharmacokinetics parameters of TAB08 after single and multiple i.v. administrations

  From study drug infusion (Day 1) untill Week 4 (Day 29)

• Proportion of patients with American College of Rheumatology (ACR) 20 (50, 70) response criteria after 4 weeks of TAB08 treatment

  From study drug infusion (Day 1) untill the Week 4 (Day 29)

• Proportion of patients with ACR20 (50, 70) response criteria after 4 weeks of TAB08 treatment at the end of study stage 1

  From study drug infusion (Day 1) untill tenf of study stage 1 (Day 85)

Study Arms (1)

TAB08

EXPERIMENTAL

Multiple TAB08 administrations as intravenous infusions.

Drug: TAB08

Interventions

TAB08 DRUG

Weekly intravenous administration in escalating doses.

Also known as: Theralizumab

TAB08

Eligibility Criteria

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

You may qualify if:

• Patients must sign and date informed consent prior to any study procedures.
• Male and female patients aged 18-65 years.
• 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.
• Patients for whom standard treatment does not result in sufficient control of symptoms of RA, per investigator opinion.
• 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.
• Active disease of RA despite standard treatment:
• At least 6 out of 66 joints are swollen and at least 6 out of 68 joints are painful.
• Level of C-reactive protein \>= 15 mg/L or erythrocyte sedimentation rate \>= 28 mm/hour or morning stiffness \> 45 minutes.
• Rheumatoid factor \> 20 IU/mL.
• Adequate hematological, renal and hepatic laboratory values.
• For men and women of childbearing potential: consent to use double barrier methods of contraception during the entire study period.

You may not qualify if:

• 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.
• Change of Methotrexate dose within 4 weeks before study treatment initiation.
• Any autoimmune disease except for rheumatoid arthritis and dry keratoconjunctivitis.
• Functional grade IV based on American College of Rheumatology scale.
• Active rheumatoid vasculitis.
• Any systemic diseases related to joint inflammation.
• Pregnant and breastfeeding women.
• Women with childbearing potential refusing to use effective contraceptive methods during the entire study period.
• Syphilis, hepatitis В, С, HIV-infection or tuberculosis based on the results of laboratory tests at Screening visit.
• Vaccination with live or attenuated vaccines within 6 weeks before the first study drug administration; planned vaccination during the study period.
• Medical history of recurrent clinically significant infections.
• Primary or secondary immunodeficiency.
• Medical history of malignant oncologic diseases except for excised basal cell skin cancer.
• 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.
• Dose change of non-steroid anti-inflammatory agents within 4 weeks before first infusion of the study drug.

Sponsors & Collaborators

• Theramab LLC: lead

Study Sites (2)

State Scientific and Research Rheumatology Institute

Moscow, 115522, Russia

Location

Clinical Emergency Hospital of Yaroslavl

Yaroslavl, 150003, Russia

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

TGN-1412

Condition Hierarchy (Ancestors)

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

Study Officials

• Daniil G Nemenov, M.D.

  Theramab LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2013
• First Posted: November 21, 2013
• Study Start: November 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: February 1, 2017
• Last Updated: February 28, 2017

Record last verified: 2017-02

Locations

RU (2)