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. (see Contacts and Locations)
Verified August 2014 by Boehringer Ingelheim
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01751776
First received: December 14, 2012
Last updated: August 20, 2014
Last verified: August 2014
  Purpose

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


Condition Intervention Phase
Arthritis, Rheumatoid
Healthy
Drug: BI 655064 medium dose
Drug: BI 655064 high dose
Drug: Placebo
Drug: BI 655064 low dose
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 (DAS28 4v-CRP and DAS 28 4v-ESR) 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 ]
  • Change in DAS28-4v at week 12 (day 85) compared to baseline (Part 2) [ Time Frame: baseline and week 12 ] [ Designated as safety issue: No ]

Estimated Enrollment: 106
Study Start Date: December 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BI 655064 Part 1
3 different doses plus placebo in healthy volunteers
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 2
2 different doses plus placebo in rheumatoid arthritis patients
Drug: BI 655064 high dose
High dose
Drug: Placebo
Placebo
Drug: BI 655064 medium dose
Medium dose

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

Part 1 (phase Ib) (HVs):

  1. Healthy males and females according to the investigator's assessment, as based on the following criteria: a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests
  2. Age >= 18 and <= 60 years
  3. Body Mass Index >= 18.5 and <= 29.9 kg/m2
  4. Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation
  5. Female subjects who meet any of the following criteria from at least 30 days before the first study drug administration and until 30 days after trial completion:

    • using adequate contraception, e.g. any of the following methods plus condom: implants, injectables, combined oral contraceptives, intrauterine device (IUD)
    • sexually abstinent
    • have a vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)
    • surgically sterilised (including hysterectomy)
    • postmenopausal defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of follicle stimulating hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory)

Part 2 (phase IIa) (RA Patients):

  1. Age >= 18 and <= 70 years
  2. Patients classified as having RA according to the 1987 ACR Classification Criteria
  3. Inadequate clinical response to methotrexate monotherapy defined as moderate/high active disease after oral or 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. For patients who do not tolerate the minimum weekly dose of at least 15 mg due to side effects, a stable weekly dose as low as 7.5 mg is also permitted.
  4. DAS28 4v-CRP >= 3.5 with >= 6 tender and >= 6 swollen joints out of 68/66 joint count at screening and confirmed by >= 6 tender and >= 6 swollen joints out of 68/66 joint count only at randomisation visit (Visit 2)
  5. Serum CRP level >= 0.8 mg/dL or ESR ¿ 28 mm/1h at screening
  6. Anti-CCP2 or Rheumatoid Factor positivity as per the limits of used assay at screening
  7. Female patients who meet any of the following criteria from at least 30 days before the first study drug administration and until at least 6 months after last dose of MTX taken in the current trial:

    using adequate contraception, e.g. any of the following methods plus condom: implants, injectables, combined oral contraceptives, intrauterine device (IUD)

    • sexually abstinent
    • have a vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)
    • surgically sterilised (including hysterectomy)
    • postmenopausal defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of follicle stimulating hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory)

    OR

    Male patients who:

    • are documented to be sterile or consistently and correctly use a condom while their female partners (if of childbearing potential) agree to use any of the following adequate contraception methods: implants, injectables, combined oral contraceptives, intrauterine device (IUD) from the date of screening until at least 6 months after the last dose of MTX taken in the current trial
    • don't donate any sperm sample for procreation purposes, from the date of screening until at least 6 months after last dose of MTX taken in the current trial.
  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

Rheumatoid 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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01751776

Contacts
Contact: Boehringer Ingelheim Call Center 1-800-243-0127 clintriage.rdg@boehringer-ingelheim.com

Locations
Czech Republic
1293.2.00030 Boehringer Ingelheim Investigational Site Recruiting
Hostivice, Czech Republic
1293.2.00049 Boehringer Ingelheim Investigational Site Not yet recruiting
Olomouc, Czech Republic
1293.2.00029 Boehringer Ingelheim Investigational Site Recruiting
Prague, Czech Republic
1293.2.00024 Boehringer Ingelheim Investigational Site Recruiting
Uherske Hradiste, Czech Republic
1293.2.00028 Boehringer Ingelheim Investigational Site Recruiting
Zlin, Czech Republic
Germany
1293.2.00015 Boehringer Ingelheim Investigational Site Recruiting
Bad Kreuznach, Germany
1293.2.00014 Boehringer Ingelheim Investigational Site Recruiting
Bad Nauheim, Germany
1293.2.00010 Boehringer Ingelheim Investigational Site Recruiting
Berlin, Germany
1293.2.00013 Boehringer Ingelheim Investigational Site Recruiting
Berlin, Germany
1293.2.00011 Boehringer Ingelheim Investigational Site Recruiting
Erlangen, Germany
1293.2.00037 Boehringer Ingelheim Investigational Site Recruiting
Hamburg, Germany
1293.2.00035 Boehringer Ingelheim Investigational Site Recruiting
Köln, Germany
1293.2.00043 Boehringer Ingelheim Investigational Site Recruiting
München, Germany
1293.2.00012 Boehringer Ingelheim Investigational Site Recruiting
Zerbst, Germany
Netherlands
1293.2.00031 Boehringer Ingelheim Investigational Site Recruiting
Amsterdam, Netherlands
1293.2.00032 Boehringer Ingelheim Investigational Site Recruiting
Leeuwarden, Netherlands
1293.2.00038 Boehringer Ingelheim Investigational Site Recruiting
Leiden, Netherlands
1293.2.00040 Boehringer Ingelheim Investigational Site Recruiting
Sneek, Netherlands
New Zealand
1293.2.00002 Boehringer Ingelheim Investigational Site Recruiting
Christchurch, New Zealand
1293.2.00001 Boehringer Ingelheim Investigational Site Recruiting
Grafton Auckland NZ, New Zealand
Poland
1293.2.00039 Boehringer Ingelheim Investigational Site Recruiting
Bialystok, Poland
1293.2.00034 Boehringer Ingelheim Investigational Site Recruiting
Bydgoszcz, Poland
1293.2.00041 Boehringer Ingelheim Investigational Site Recruiting
Bydgoszcz, Poland
1293.2.00025 Boehringer Ingelheim Investigational Site Recruiting
Lublin, Poland
1293.2.00023 Boehringer Ingelheim Investigational Site Recruiting
Warsaw, Poland
1293.2.00026 Boehringer Ingelheim Investigational Site Recruiting
Warszawa, Poland
Spain
1293.2.00021 Boehringer Ingelheim Investigational Site Recruiting
A Coruña, Spain
1293.2.00017 Boehringer Ingelheim Investigational Site Recruiting
Barcelona, Spain
1293.2.00018 Boehringer Ingelheim Investigational Site Recruiting
Córdoba, Spain
1293.2.00019 Boehringer Ingelheim Investigational Site Recruiting
El Palmar - Murcia, Spain
1293.2.00022 Boehringer Ingelheim Investigational Site Recruiting
Granada, Spain
1293.2.00016 Boehringer Ingelheim Investigational Site Recruiting
La Laguna (Sta Cruz Tenerife), Spain
1293.2.00042 Boehringer Ingelheim Investigational Site Recruiting
Sabadell, Spain
1293.2.00020 Boehringer Ingelheim Investigational Site Recruiting
Santiago de Compostela, Spain
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01751776     History of Changes
Other Study ID Numbers: 1293.2, 2012-004090-16
Study First Received: December 14, 2012
Last Updated: August 20, 2014
Health Authority: Australia: Human Research Ethics Committee
Czech Republic: State Institute for Drug Control
Germany: Paul-Ehrlich-Institut
Netherlands: Central Committee Research Involving Human Subjects
New Zealand: Medsafe
Poland: Registration Medicinal Product Medical Device Biocidal Product
Romania: National Medicines Agency
Spain: Spanish Agency of Medicines

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 27, 2014