Study Evaluating Multiple Ascending Doses Of ATN-103 In Japanese Subjects With Rheumatoid Arthritis

NCT01007175 | Completed Phase 1

• 2 other identifiers: 3242K1-2001B2271004
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 15

Brief Summary

This primary purpose of this study is to evaluate the safety, tolerability, and pharmacokinetic properties of multiple ascending doses of ATN-103 administered subcutaneously (below the skin) to Japanese subjects with active rheumatoid arthritis and on a stable background of methotrexate. Some subjects will receive ATN-103 while other subjects will receive a placebo.

Conditions

Rheumatoid Arthritis

Keywords

TNF inhibitor; Multiple ascending dose study

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability will be evaluated on the basis of AEs, SAEs,(including injection site reactions and infections), physical examination findings, vital sign, measurements, immunogenicity assessments, early termination, and clinical laboratory test.

  20 weeks

Secondary Outcomes (1)

• Clinical efficacy for Rheumatoid Arthritis (RA) based on ACR responses, ACR-N, DAS 28 and EULAR response.

  16 weeks

Study Arms (5)

Cohort 1

EXPERIMENTAL

Biological: ATN-103 10 mg q4wks

Cohort 2

EXPERIMENTAL

Biological: ATN-103 30 mg q4wks

Cohort 3

EXPERIMENTAL

Biological: ATN-103 80 mg q4wks

Cohort 4

EXPERIMENTAL

Biological: ATN-103 10 mg q8wks

Cohort 5

EXPERIMENTAL

Biological: ATN-103 80 mg q8wks

Interventions

ATN-103 10 mg q4wks BIOLOGICAL

ATN-103 160-mg vials (lyophilized) and placebo vials (lyophilized) Each subject will be given a single SC injection (0.1 mL) of either ATN-103 or placebo at 4-week intervals for a total of 4 SC injections.

Cohort 1

ATN-103 30 mg q4wks BIOLOGICAL

ATN-103 160-mg vials (lyophilized) and placebo vials (lyophilized) Each subject will be given a single SC injection (0.3 mL) of either ATN-103 or placebo at 4-week intervals for a total of 4 SC injections.

Cohort 2

ATN-103 80 mg q4wks BIOLOGICAL

ATN-103 160-mg vials (lyophilized) and placebo vials (lyophilized) Each subject will be given a single SC injection (0.8 mL) of either ATN-103 or placebo at 4-week intervals for a total of 4 SC injections.

Cohort 3

ATN-103 10 mg q8wks BIOLOGICAL

ATN-103 160-mg vials (lyophilized) and placebo vials (lyophilized) Each subject will be given a single SC injection (0.1 mL) of either ATN-103 or placebo at 8-week intervals for a total of 2 SC injections.

Cohort 4

ATN-103 80 mg q8wks BIOLOGICAL

ATN-103 160-mg vials (lyophilized) and placebo vials (lyophilized) Each subject will be given a single SC injection (0.8 mL) of either ATN-103 or placebo at 8-week intervals for a total of 2 SC injections.

Cohort 5

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meets the ACR 1987 revised criteria for classification of Rheumatoid Arthritis (RA).
• ACR functional class I through III.
• Active RA at the time of screening and at baseline consisting of = 6 swollen and = 6 tender joints at least.
• hs-CRP level = 8 mg/L.
• Must be receiving MTX for at least 12 wks, with a stable dose and route of MTX for at least 6 wks prior to the baseline and continuing on that dose for the duration of the study.
• The report of a chest x-ray performed within 12 wks before the screening documenting the absence of any evidence of malignancy, infection, or abnormalities suggestive of TB must be obtained and available in the subject's study file prior to baseline.
• All WOCBP must have a negative pregnancy test result at screening and baseline.
• All WOCBP who have sexual intercourse with a nonsurgically sterilized male partner must agree and commit to the use of the following highly effective forms of contraception for the duration of the study and for 8 wks after the last dose of investigational product.
• All male subjects who are biologically capable of fathering children must agree and commit to the use of a reliable method of birth control for the duration of the study and for 8 wks after the last dose of investigational product.

You may not qualify if:

• Pregnant or breastfeeding women.
• Presence of active infections or open cutaneous ulcers or any underlying disease that could predispose subjects to infections or history of serious infection within 4 wks before the baseline.
• A history or current evidence of latent or active TB, evidence of prior or currently active TB by chest X-ray, recent close contact with an individual with active TB, or a positive Mantoux tuberculin skin test.
• Other significant concurrent medical conditions at the time of the screening or baseline.
• Laboratory abnormalities at screening. Positive for HBsAg, HBcAb, and/or HepCAb. ALTand/or AST= 2 times the ULN or higher. Hemoglobin = 8.5 g/dL or lower. Platelet = 125,000 /mm³ or lower, or = 1,000,000 /mm³ or higher. WBC = 3500 /mm³ or lower. Serum creatinine= 2 mg/dL or higher.
• Any prior use of B cell-depleting therapy.
• Receipt within 24 wks before the baseline visit:
• Any cytotoxic drugs. Leflunomide. Any investigational biological drug(s).
• Etanercept. IA hyaluronic acid injections. Any live (attenuated) vaccine.
• Receipt within 2 wks before the baseline: \> 10 mg/day of oral prednisone or equivalent, or change in the dose of oral prednisone or its equivalent.
• IA, bolus IM, or IV treatment with corticosteroids. \> 1 NSAID, change of dose of the NSAID, or NSAID use greater than the maximum recommended dose.
• Initiation of statins or dosage adjustment to a current statin. Change in the dose of folic acid.
• Known or suspected allergy to ATN-103, any type of TNF inhibitors, human immunoglobulin proteins, or other compounds related to these classes of medication.
• Current or history of psychiatric disease or alcohol or drug abuse that, in the opinion of the investigator, would interfere with the ability to comply with the study protocol or give informed consent.

Sponsors & Collaborators

• Ablynx, a Sanofi company: lead

Study Sites (15)

Investigational Site

Chiba, Japan

Location

Investigational Site

Ehime, Japan

Location

Investigational Site

Fukuoka, Japan

Location

Investigational Site

Gunma, Japan

Location

Investigational Site

Hyōgo, Japan

Location

Investigational Site

Kumamoto, Japan

Location

Investigational Site

Kyoto, Japan

Location

Investigational Site

Miyazaki, Japan

Location

Investigational Site

Nagano, Japan

Location

Investigational Site

Nagasaki, Japan

Location

Investigational Site

Osaka, Japan

Location

Investigational Site

Saga, Japan

Location

Investigational Site

Saitama, Japan

Location

Investigational Site

Tokyo, Japan

Location

Investigational Site

Toyama, Japan

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 Officials

• Josefin-Beate Holz

  Ablynx, a Sanofi company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2009
• First Posted: November 3, 2009
• Study Start: November 1, 2009
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: September 4, 2013

Record last verified: 2013-01

Locations

JP (15)