A Trial to Evaluate the Safety and Tolerability of MT203 in Patients With Mild to Moderate Rheumatoid Arthritis (PRIORA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01317797
First received: February 18, 2011
Last updated: August 20, 2013
Last verified: August 2013
  Purpose

The purpose of this trial is primarily to investigate the safety and tolerability of repeated subcutaneous injections of MT203 in patients with mild to moderate rheumatoid arthritis. Furthermore, the amount of MT203 in the blood will be measured and it will be investigated how the body responds to MT203 treatment and if MT203 is effective in the treatment of rheumatoid arthritis.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: MT203
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase Ib Double-blind, Placebo-controlled, Randomized, Dose-escalating Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Repeated Subcutaneous Injections of MT203 in Patients With Mild to Moderate Rheumatoid Arthritis on Treatment With Methotrexate

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Safety and tolerability as assessed by clinical laboratory (haematology, chemistry, coagulation, urinalysis) [ Time Frame: Average up to 113 days after first IMP (Investigational Medicinal Product) administration ] [ Designated as safety issue: Yes ]
    To evaluate the safety and tolerability of repeated subcutaneous injections of MT203 in patients with mild to moderate rheumatoid arthritis.

  • Safety and tolerability as assessed by electrocardiogram [ Time Frame: Average up to 113 days after first IMP administration ] [ Designated as safety issue: Yes ]
    To evaluate the safety and tolerability of repeated subcutaneous injections of MT203 in patients with mild to moderate rheumatoid arthritis.

  • Safety and tolerability as assessed by vital signs [ Time Frame: Average up to 113 days after first IMP administration ] [ Designated as safety issue: Yes ]
    To evaluate the safety and tolerability of repeated subcutaneous injections of MT203 in patients with mild to moderate rheumatoid arthritis.

  • Safety and tolerability as assessed by pulmonary function [ Time Frame: Average up to 113 days after first IMP administration ] [ Designated as safety issue: Yes ]
    To evaluate the safety and tolerability of repeated subcutaneous injections of MT203 in patients with mild to moderate rheumatoid arthritis.

  • Safety and tolerability as assessed by physical examination [ Time Frame: Average up to 113 days after first IMP administration ] [ Designated as safety issue: Yes ]
    To evaluate the safety and tolerability of repeated subcutaneous injections of MT203 in patients with mild to moderate rheumatoid arthritis.

  • Safety and tolerability as assessed by adverse events [ Time Frame: Average up to 113 days after first IMP administration ] [ Designated as safety issue: Yes ]
    To evaluate the safety and tolerability of repeated subcutaneous injections of MT203 in patients with mild to moderate rheumatoid arthritis.


Secondary Outcome Measures:
  • MT203 concentration in the blood (pharmacokinetics) [ Time Frame: Average up to 113 days after first IMP administration ] [ Designated as safety issue: No ]
    To evaluate the pharmacokinetics of repeated subcutaneous injections of MT203 in patients with mild to moderate rheumatoid arthritis

  • GM-CSF in plasma, MT203/GM-CSF complexes in plasma, immunogenicity in blood (pharmacodynamics) [ Time Frame: Average up to 113 days after first IMP administration ] [ Designated as safety issue: No ]
    To evaluate the pharmacodynamics of repeated subcutaneous injections of MT203 in patients with mild to moderate rheumatoid arthritis

  • Biomarkers in the blood (cytokines and inflammatory proteins) will be assessed exploratively [ Time Frame: Average up to 113 days after first IMP administration ] [ Designated as safety issue: No ]
    To evaluate the biomarkers of repeated subcutaneous injections of MT203 in patients with mild to moderate rheumatoid arthritis

  • First signal of efficacy of repeated doses assessed by ACR and Disease Activity Score (DAS), pharmacokinetics, pharmacodynamics, and explorative biomarkers [ Time Frame: Average up to 113 days after first IMP administration ] [ Designated as safety issue: No ]
    To evaluate the efficacy of repeated subcutaneous injections of MT203 in patients with mild to moderate rheumatoid arthritis.


Enrollment: 24
Study Start Date: March 2011
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: MT203 Drug: MT203
administered three times, subcutaneous in the abdomen
Placebo Comparator: Placebo Drug: Placebo
administered three times, subcutaneous in the abdomen

Detailed Description:

The trial medication will be administered at 2 dose levels as subcutaneous injections. Each patient will receive three injections in total. The trial duration consists of a screening period (28 - 2 days prior to the first injection) and a treatment and observation period (4 months). The trial requires approximately 20 visits at the study site.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Out-patients with active rheumatoid arthritis (RA), according to the ACR 1987 revised criteria, with low to moderate disease activity (DAS28-ESR ≥ 2.6 and ≤ 5.1)
  2. Patients must be on stable doses of methotrexate (MTX) ≥ 7.5 and ≤ 25 mg/week for at least 12 weeks before the first injection, with appropriate folic acid supplementation
  3. Age ≥ 18 years at Screening
  4. Body weight at least 50 kg at Screening; BMI: ≥ 18.0 and ≤ 30.0 kg/m2 at Screening
  5. Negative tuberculosis test at Screening
  6. Heterosexually active male and female patients of childbearing potential are obliged to follow whatever contraceptive and / or breastfeeding restrictions may be required for their concomitant medication(s), including methotrexate.

In addition, heterosexually active male and female patients of childbearing potential are required to use effective double-method contraception (one hormonal contraceptive or intrauterine device and one other additional contraceptive method) for 1 month before the first administration of the IMP, during the course of the trial, and for 6 month after the last injection of MT203.

No special requirements are made for female patients proven to be post-menopausal (at least 2 years after last menstrual period and FSH ≥ 40IU/L), surgically sterilized or hysterectomized. Likewise no special requirements for heterosexually active male who are surgical sterilized.

Pregnant or lactating female patients have to be excluded.

Exclusion Criteria:

  1. Participation in another clinical trial or previous dosing in this trial
  2. Use of specified medications within certain timeframes or use of certain comedications
  3. History or presence of specified diseases
  4. Drug abuse
  5. Certain laboratory parameters outside a specified range
  6. Donation of blood
  7. Relevant decrease in lung function
  8. Infections, frequent or chronic infections, herpes zoster
  9. Females: positive pregnancy test
  10. Presence of history of tuberculosis
  11. History of malignancy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01317797

Locations
Bulgaria
Nycomed Investigational Site
Sofia, Bulgaria
Netherlands
Nycomed Investigational Site
Leids, Netherlands
Sponsors and Collaborators
Takeda
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01317797     History of Changes
Other Study ID Numbers: M1-1188-002-EM, 2010-018502-36, U1111-1137-3923, NL33507.058.10
Study First Received: February 18, 2011
Last Updated: August 20, 2013
Health Authority: Bulgaria: Bulgarian Drug Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Takeda:
Rheumatoid Arthritis
MT203
Human IgG1 monoclonal antibody
GM-CSF monoclonal antibody

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014