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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01751776




Registration number
NCT01751776
Ethics application status
Date submitted
14/12/2012
Date registered
18/12/2012
Date last updated
12/05/2015

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2012-004090-16
Secondary ID [2] 0 0
1293.2
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Arthritis, Rheumatoid 0 0
Healthy 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BI 655064 medium dose
Treatment: Drugs - BI 655064 high dose
Treatment: Drugs - BI 655064 high dose
Treatment: Drugs - Placebo
Treatment: Drugs - BI 655064 low dose
Treatment: Drugs - Placebo
Treatment: Drugs - BI 655064 medium dose

Experimental: BI 655064 Part 1 - 3 different doses plus placebo in healthy volunteers

Experimental: BI 655064 Part 2 - 2 different doses plus placebo in rheumatoid arthritis patients


Treatment: Drugs: BI 655064 medium dose
Medium dose

Treatment: Drugs: BI 655064 high dose
High dose

Treatment: Drugs: BI 655064 high dose
High dose

Treatment: Drugs: Placebo
Placebo

Treatment: Drugs: BI 655064 low dose
Low dose

Treatment: Drugs: Placebo
Placebo

Treatment: Drugs: BI 655064 medium dose
Medium dose

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Primary PK endpoint (Part 1): Cmax (after first and 4th dose)
Timepoint [1] 0 0
up to Day 64 post-treatment
Primary outcome [2] 0 0
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)
Timepoint [2] 0 0
Up to Day 64 post-treatment
Primary outcome [3] 0 0
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)
Timepoint [3] 0 0
Up to Day 64 post-treatment
Primary outcome [4] 0 0
Number of subjects with drug related Adverse Events (Part 1).
Timepoint [4] 0 0
Up to Day 64 post-treatment
Primary outcome [5] 0 0
ACR20 (American College of Rheumatology) response rate at week 12 (day 85) from the initiation of study treatment (Part 2)
Timepoint [5] 0 0
week 12
Secondary outcome [1] 0 0
ACR50 and 70 response rates at week 12 (day 85) (Part 2)
Timepoint [1] 0 0
week 12
Secondary outcome [2] 0 0
EULAR (European League Against Rheumatism) response criteria (DAS28 4v-CRP and DAS 28 4v-ESR) at week 12 (day 85) (Part 2)
Timepoint [2] 0 0
week 12
Secondary outcome [3] 0 0
Percentage of patients with a decrease in DAS28 4v-CRP of >1.2 at week 12 (day 85) compared to baseline (Part 2)
Timepoint [3] 0 0
baseline and week 12
Secondary outcome [4] 0 0
Change in DAS28-4v at week 12 (day 85) compared to baseline (Part 2)
Timepoint [4] 0 0
baseline and week 12

Eligibility
Key inclusion criteria
Inclusion criteria:

Part 1 (phase Ib) (HVs):

1. Healthy males and females according to the investigators 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
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria:

Part 1 (phase Ib in HVs):

1. Any finding in the medical examination (including BP, PR or ECG) deviating from normal
and judged clinically relevant by the investigator

2. Any laboratory value outside the reference range that the investigator considers to be
of clinical relevance

3. Any evidence of a concomitant disease judged clinically relevant by the investigator

4. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,
immunological or hormonal disorders

5. Diseases of the central nervous system (such as epilepsy), other neurological
disorders or psychiatric disorders

6. History of relevant orthostatic hypotension, fainting spells, or blackouts

7. History of relevant allergy/hypersensitivity (including allergy to the trial
medication or its excipients)

9. Within 10 days prior to administration of trial medication, use of drugs that might
reasonably influence the results of the trial 12. Alcohol abuse (consumption of more than
140 g/week in females and 210 g/week in males) 13. Drug abuse or positive drug screen 17.
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) 18. 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 19. Positive pregnancy test, pregnancy
or plans to become pregnant within 30 days after study completion 20. Lactation

Further exclusion criteria applicable for part 1 only are given in the CTP.

Part 2 (phase IIa in RA patients):

Part 1 (phase Ib) exclusion criteria 7, 9, 12, 13 and 17-20 plus:

1. Current or previous use of more than two anti-TNF biologic drugs or use of other
biologic agent targeting any other approved mechanism (any biologic drug with
mechanism of action other than direct anti-TNF blockade, (e.g. CTLA4, anti-IL6, or
anti CD-20) or new oral compounds targeting any other approved mechanism (e.g. JAK
inhibitors) for treating RA.

2. Current or previous participation in a clinical trial testing an investigational drug
for RA within 3 months prior to screening or within 5 half-lives of the
investigational drug, whichever is longer , except of previous participation in trials
testing NSAIDs, corticosteroids, analgesics or patients documented as receiving
placebo in previous RA trials.

3. DAS28 < 3.2 in at least 2 occasions during the last 6 months before screening

4. RA patients with severe disability (functional class IV) or with confirmed severe
systemic manifestations e.g. known amyloidosis, Felty´s syndrome, lymphoproliferative
disorders, rheumatoid vasculitis

5. Treatment with any standard DMARD except MTX (including but not limited to
sulfasalazine, leflunomide, hydroxychloroquine, D-penicillamine

6. Impaired hepatic function, defined as serum AST/ALT, bilirubin or alkaline phosphatase
levels > 2 x ULN

7. Impaired renal function defined as calculated creatinine clearance < 50ml/min

8. Pre-existing blood dyscrasias e.g. bone marrow hypoplasia, significant anaemia,
leucopenia or thrombocytopenia

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 within the last
5 years before screening, except appropriately treated basal cell carcinoma of the
skin or in situ carcinoma of uterine cervix.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Czech Republic
State/province [1] 0 0
Olomouc
Country [2] 0 0
Czech Republic
State/province [2] 0 0
Uherske Hradiste
Country [3] 0 0
Czech Republic
State/province [3] 0 0
Zlin
Country [4] 0 0
Germany
State/province [4] 0 0
Bad Kreuznach
Country [5] 0 0
Germany
State/province [5] 0 0
Berlin
Country [6] 0 0
Germany
State/province [6] 0 0
München
Country [7] 0 0
Germany
State/province [7] 0 0
Zerbst
Country [8] 0 0
Netherlands
State/province [8] 0 0
Amsterdam
Country [9] 0 0
Netherlands
State/province [9] 0 0
Leeuwarden
Country [10] 0 0
Netherlands
State/province [10] 0 0
Leiden
Country [11] 0 0
Netherlands
State/province [11] 0 0
Sneek
Country [12] 0 0
New Zealand
State/province [12] 0 0
Grafton Auckland NZ
Country [13] 0 0
Poland
State/province [13] 0 0
Bialystok
Country [14] 0 0
Poland
State/province [14] 0 0
Bydgoszcz
Country [15] 0 0
Poland
State/province [15] 0 0
Lublin
Country [16] 0 0
Poland
State/province [16] 0 0
Poznan
Country [17] 0 0
Poland
State/province [17] 0 0
Warsaw
Country [18] 0 0
Poland
State/province [18] 0 0
Warszawa
Country [19] 0 0
Spain
State/province [19] 0 0
A Coruña
Country [20] 0 0
Spain
State/province [20] 0 0
Barcelona
Country [21] 0 0
Spain
State/province [21] 0 0
Granada
Country [22] 0 0
Spain
State/province [22] 0 0
La Laguna (Sta Cruz Tenerife)
Country [23] 0 0
Spain
State/province [23] 0 0
Santiago de Compostela

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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
655064 in healthy volunteers (HVs) and rheumatoid arthritis (RA) patients. To assess clinical
effect of BI 655064 in RA patients with prior inadequate response to methotrexate (MTX) after
12 weeks of treatment
Trial website
https://clinicaltrials.gov/show/NCT01751776
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Boehringer Ingelheim
Address 0 0
Boehringer Ingelheim
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications