Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Effects of Multiple Rising Subcutaneous Doses of BI 655064 in Healthy Volunteers and in Rheumatoid Arthritis Patients With Prior Inadequate Response to Methotrexate Therapy

This study is currently recruiting participants.
Verified April 2014 by Boehringer Ingelheim
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01751776
First received: December 14, 2012
Last updated: April 2, 2014
Last verified: April 2014

December 14, 2012
April 2, 2014
December 2012
October 2014   (final data collection date for primary outcome measure)
  • Primary PK endpoint (Part 1): Cmax (after first and 4th dose) [ Time Frame: up to Day 64 post-treatment ] [ Designated as safety issue: No ]
  • Primary PK endpoint (Part 1): AUC 0-infinity (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinite) [ Time Frame: Up to Day 64 post-treatment ] [ Designated as safety issue: No ]
  • Primary PK endpoint (Part 1): AUC t,4 (Area under the concentration-time curve of the analyte in plasma after the 4th dose over a uniform dosing interval t) after the first and 4th dose) [ Time Frame: Up to Day 64 post-treatment ] [ Designated as safety issue: No ]
  • Number of subjects with drug related Adverse Events (Part 1). [ Time Frame: Up to Day 64 post-treatment ] [ Designated as safety issue: No ]
  • ACR20 (American College of Rheumatology) response rate at week 12 (day 85) from the initiation of study treatment (Part 2) [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • Percentage of patients with a decrease in DAS28 4v-CRP of >1.2 at week 12 (day 85) compared to baseline [ Time Frame: baseline and week 12 ] [ Designated as safety issue: No ]
  • ACR50 and 70 response rates at week 12 (day 85) [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • ACR20 (American College of Rheumatology) response rate at week 12 (day 85) from the initiation of study treatment [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • EULAR (European League Against Rheumatism) response criteria measured as the disease activity score with four variables including c-reactive protein (DAS28 4v-CRP) at week 12 (day 85) [ Time Frame: week 12 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01751776 on ClinicalTrials.gov Archive Site
  • ACR50 and 70 response rates at week 12 (day 85) (Part 2) [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • EULAR (European League Against Rheumatism) response criteria measured as the disease activity score with four variables including c-reactive protein (DAS28 4v-CRP) at week 12 (day 85) (Part 2) [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  • Percentage of patients with a decrease in DAS28 4v-CRP of >1.2 at week 12 (day 85) compared to baseline (Part 2) [ Time Frame: baseline and week 12 ] [ Designated as safety issue: No ]
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Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Effects of Multiple Rising Subcutaneous Doses of BI 655064 in Healthy Volunteers and in Rheumatoid Arthritis Patients With Prior Inadequate Response to Methotrexate Therapy
A Randomised, Double-blind, Placebo-controlled Trial for Establishing Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Efficacy of Multiple Subcutaneous Doses of BI 655064 in Healthy Volunteers and in Rheumatoid Arthritis Patients With Prior Inadequate Response to Methotrexate Therapy

To evaluate the safety and tolerability of multiple doses of BI 655064 administered subcutaneously in healthy volunteers (HVs) and in rheumatoid arthritis (RA) patients. To explore the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of multiple doses of BI 655604 in healthy volunteers (HVs) and rheumatoid arthritis (RA) patients. To assess clinical effect of BI 655604 in RA patients with prior inadequate response to methotrexate (MTX) after 12 weeks of treatment

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
  • Arthritis, Rheumatoid
  • Healthy
  • Drug: BI 655064 medium dose
    Medium dose
  • Drug: BI 655064 high dose
    High dose
  • Drug: Placebo
    Placebo
  • Drug: BI 655064 low dose
    Low dose
  • Experimental: BI 655064 Part 1
    3 different doses plus placebo in healthy volunteers
    Interventions:
    • Drug: BI 655064 medium dose
    • Drug: BI 655064 high dose
    • Drug: Placebo
    • Drug: BI 655064 low dose
  • Experimental: BI 655064 Part 2
    2 different doses plus placebo in rheumatoid arthritis patients
    Interventions:
    • Drug: BI 655064 high dose
    • Drug: Placebo
    • Drug: BI 655064 medium dose
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
106
December 2014
October 2014   (final data collection date for primary outcome measure)

Inclusion criteria:

Healthy Volunteers (HVs) in Part 1:

  1. Healthy males and females according to the investigator¿s assessment (females of child-bearing potential must be using effective contraception)
  2. Age 18 - 60 years
  3. Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation

Rheumatoid Arthritis (RA) patients in Part 2:

  1. Age 18 - 70 years
  2. Classified as having RA according to the 1987 American College of Rheumatology (ACR) Classification Criteria
  3. <5 years from RA diagnosis to screening
  4. Inadequate clinical response to methotrexate (MTX) monotherapy defined as moderate/high active disease after oral or subcutaneous (s.c.) MTX treatment given continuously for at least 3 months and for the last 6 weeks before screening at a stable weekly dose >15mg.
  5. DAS28 4v-CRP >3.5 with >6 tender and >6 swollen joints at screening and confirmed by >6 tender and >6 swollen joints at randomisation visit (Visit 2)
  6. Serum CRP level =1.0 mg/dL at screening
  7. Anti-CCP2 positivity according to the limits of the assay used
  8. Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation

Exclusion criteria:

Healthy Volunteers (HVs) in Part 1:

1. Any finding on clinical examination/history or laboratory value which deviates from normality and has clinical significance

Rheumatiod Arthritis (RA) pts in Part 2:

1. Current or previous use of an approved biologic agent 2. Current or previous participation in a clinical trial testing an investigational drug for RA 3. Disease activity score (DAS)28 < 3.2 in at least 2 occasions during the last 6 months before screening 4. Treatment with any standard disease modifying anti-rheumatic drug (DMARD) except methotrexate (MTX) continuing after randomisation 5. RA patients with severe disability (functional class IV) or with confirmed severe systemic manifestations 6. Impaired hepatic or renal function 8. Pre-existing blood dyscrasias 9. Hypersensitivity to MTX or any of its excipients 10. Previous intolerance to MTX as the main cause for stopping treatment (instead of lack of efficacy) 11. Any active or suspected malignancy or history of documented malignancy, except appropriately 12. Chronic or relevant acute infections, including but not limited to HIV, Hepatitis B and C and tuberculosis (including a history of clinical TB and/or a positive QuantiFERON TB-Gold test) treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix.

13. Subject is assessed by the investigator as unsuitable for inclusion e.g. considered not able to understand and comply with study requirements or has a condition that would not allow safe participation in the study

Both
18 Years to 70 Years
Yes
Contact: Boehringer Ingelheim Call Center 1-800-243-0127 clintriage.rdg@boehringer-ingelheim.com
Czech Republic,   Germany,   Netherlands,   New Zealand,   Poland,   Spain
 
NCT01751776
1293.2, 2012-004090-16
Not Provided
Boehringer Ingelheim
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Boehringer Ingelheim
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP