Arthritis, RheumatoidPhase 1NCT01751776
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 Phase 1 study testing BI 655064 in people with Arthritis, Rheumatoid and Healthy, run by Boehringer Ingelheim at 25 sites in 6 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Arthritis, Rheumatoid, Healthy
- What is being tested?
- BI 655064
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 107 participants
- Where
- 25 sitesin 6 countries
- Study dates
- 18 Dec 2012to 27 Apr 2015
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Part 1 (phase Ib) (HVs):
- 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
- Age >= 18 and <= 60 years
- Body Mass Index >= 18.5 and <= 29.9 kg/m2
- Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation
- 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:
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- 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):
- Age >= 18 and <= 70 years
- Patients classified as having RA according to the 1987 ACR Classification Criteria
- 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.
- 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)
- Serum CRP level >= 0.8 mg/dL or ESR >= 28 mm/1h at screening
- Anti-CCP2 or Rheumatoid Factor positivity as per the limits of used assay at screening
- 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.
- Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation
Who cannot join
- Part 1 (phase Ib in HVs):
- Any finding in the medical examination (including BP, PR or ECG) deviating from normal and judged clinically relevant by the investigator
- Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
- Any evidence of a concomitant disease judged clinically relevant by the investigator
- Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- Diseases of the central nervous system (such as epilepsy), other neurological disorders or psychiatric disorders
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- History of relevant orthostatic hypotension, fainting spells, or blackouts
- 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:
- 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.
- 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.
- DAS28 < 3.2 in at least 2 occasions during the last 6 months before screening
- 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
- Treatment with any standard DMARD except MTX (including but not limited to sulfasalazine, leflunomide, hydroxychloroquine, D-penicillamine
- Impaired hepatic function, defined as serum AST/ALT, bilirubin or alkaline phosphatase levels > 2 x ULN
- Impaired renal function defined as calculated creatinine clearance < 50ml/min
- Pre-existing blood dyscrasias e.g. bone marrow hypoplasia, significant anaemia, leucopenia or thrombocytopenia
- Hypersensitivity to MTX or any of its excipients
- Previous intolerance to MTX as the main cause for stopping treatment (instead of lack of efficacy)
- 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.
Trial locations and contacts
25 sites in 6 countries.
25 sites in 6 countries
Poland7 sites
1293.2.00039 Boehringer Ingelheim Investigational Site
Bialystok
1293.2.00034 Boehringer Ingelheim Investigational Site
Bydgoszcz
1293.2.00041 Boehringer Ingelheim Investigational Site
Bydgoszcz
1293.2.00025 Boehringer Ingelheim Investigational Site
Lublin
1293.2.00050 Boehringer Ingelheim Investigational Site
Poznan
1293.2.00023 Boehringer Ingelheim Investigational Site
Warsaw
1293.2.00026 Boehringer Ingelheim Investigational Site
Warsaw
Germany5 sites
1293.2.00015 Boehringer Ingelheim Investigational Site
Bad Kreuznach
1293.2.00010 Boehringer Ingelheim Investigational Site
Berlin
1293.2.00013 Boehringer Ingelheim Investigational Site
Berlin
1293.2.00043 Boehringer Ingelheim Investigational Site
München
1293.2.00012 Boehringer Ingelheim Investigational Site
Zerbst
Spain5 sites
1293.2.00021 Boehringer Ingelheim Investigational Site
A Coruña
1293.2.00017 Boehringer Ingelheim Investigational Site
Barcelona
1293.2.00022 Boehringer Ingelheim Investigational Site
Granada
1293.2.00016 Boehringer Ingelheim Investigational Site
La Laguna (Sta Cruz Tenerife)
1293.2.00020 Boehringer Ingelheim Investigational Site
Santiago de Compostela
Netherlands4 sites
1293.2.00031 Boehringer Ingelheim Investigational Site
Amsterdam
1293.2.00032 Boehringer Ingelheim Investigational Site
Leeuwarden
1293.2.00038 Boehringer Ingelheim Investigational Site
Leiden
1293.2.00040 Boehringer Ingelheim Investigational Site
Sneek
Czechia3 sites
1293.2.00049 Boehringer Ingelheim Investigational Site
Olomouc
1293.2.00024 Boehringer Ingelheim Investigational Site
Uherské Hradiště
1293.2.00028 Boehringer Ingelheim Investigational Site
Zlín
New Zealand1 site
1293.2.00001 Boehringer Ingelheim Investigational Site
Grafton Auckland NZ
About this study
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
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
- Conditions
- Arthritis, Rheumatoid, Healthy
- Being tested
- Placebo matching BI 655064, BI 655064
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo matching BI 655064Drug
Placebo matching BI 655064 injected subcutaneous.
BI 655064Drug
BI 655064 injected subcutaneous
| Study group | Role | What they receive |
|---|---|---|
| Part 1, Placebo BI 655064 80/120mg (HV) | Placebo comparator | Part 1, Healthy volunteers (HV): Placebo matching BI 655064 80 or 120 milligram (mg) injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. Receives: Drug: Placebo matching BI 655064 |
| Part 1, Placebo BI 655064 180/240mg (HV) | Placebo comparator | Part 1, Healthy volunteers (HV): Placebo matching BI 655064 180 or 240 mg injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks (180mg dosing group) or 8 weeks (240mg dosing group) follow-up period. Receives: Drug: Placebo matching BI 655064 |
| Part 1, BI 655064 80mg (HV) | Experimental | Part 1, Healthy volunteers (HV): 80 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. Receives: Drug: BI 655064 |
| Part 1, BI 655064 120mg (HV) | Experimental | Part 1, Healthy volunteers (HV): 120 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. Receives: Drug: BI 655064 |
| Part 1, BI 655064 180mg (HV) | Experimental | Part 1, Healthy volunteers (HV): 180 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. Receives: Drug: BI 655064 |
| Part 1, BI 655064 240mg (HV) | Experimental | Part 1, Healthy volunteers (HV): 240mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 8 weeks follow-up period. Receives: Drug: BI 655064 |
| Part 2, Placebo BI 655064 120mg (RA) | Placebo comparator | Part 2, patients with Rheumatoid arthritis (RA) who had prior inadequate response to Methotrexat (MTX) therapy: Placebo matching BI 655064 120 milligram (mg) injected subcutaneous on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (once weekly for 12 weeks) followed by 8 weeks follow-up period. Receives: Drug: Placebo matching BI 655064 |
| Part 2, BI 655064 120mg (RA) | Experimental | Part 2, patients with RA who had prior inadequate response to MTX therapy: 120 milligram (mg) of BI 655064 injected subcutaneous on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (once weekly for 12 weeks) followed by 8 weeks follow-up period. Receives: Drug: BI 655064 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Cmax After the First and Last Dose
Part 1: This outcome measure presents the maximum measured concentration of BI 655064 in plasma (Cmax) after the first and last (fourth) dose. More detailed time frame: Pharmacokinetic (PK) sample times: 0:30 hour (h) prior first administration of BI 655064 and 1 h, 8 h, 12 h, 24 h, 48 h, 72 h, 84 h, 96 h, 108 h, 120 h, 144 h, 167:30 h, 335:30 h, 503:30 h, 505 h, 516 h, 528 h, 552 h, 576 h, 600 h, 624 h, 648 h, 672 h, 696 h, 744 h, 816 h, 912 h, 1008 h, 1176 h, 1344 h, 1512 h, 1848 h thereafter; further administration times for BI 655064: 168 h, 336 h, and 504 h after first administration.
Measured: From first day of drug administration till end of trial, up to 77 days. Detailed PK can be found in the endpoint description.
Part 1: AUC 0-infinity After the Last Dose
Part 1: Area under the concentration-time curve of BI 655064 in plasma over the time interval from 0 extrapolated to infinite (AUC 0-infinity).
Measured: PK sample times: 1 h, 12 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 192 h, 240 h, 312 h, 408 h, 504 h, 672 h, 840 h, 1008 h, 1344 h after the last administration of BI 655064 on day 22
Part 1: AUCtau After the Last Dose
Area under the concentration-time curve of BI 655064 in plasma after the 4th dose over a uniform dosing interval t (AUC t,4) after the first and 4th dose. AUCtau is synonymous with AUC0-168.
Measured: PK sample times: 1 h, 12 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 192 h, 240 h, 312 h, 408 h, 504 h, 672 h, 840 h, 1008 h, 1344 h after the last administration of trial drug on day 22
Part 1: Percentage of Subjects With Drug Related Adverse Events
In Part 1 (Phase Ib): The primary safety endpoint was the percentage of subjects with AEs related to treatment with trial medication.
Measured: from first administration of study medication (day 1) up to day 64 (dosing groups 80, 120, 180mg) or up to day 78 post-treatment (dosing group 240mg)
Part 2: American College of Rheumatology (ACR)20 Response Rate at Week 12
ACR 20 criteria at week 12 relative to the patient's status at baseline: that is, at least 20 percent (%) improvement in swollen joint count, at least 20% improvement in tender joint count, and at least 20% improvement in ≥3 of the following 5 variables: 1) patient's assessment of pain on the visual analogue scale (VAS), rated on a scale of 1 to 10; 2) patient's global assessment of disease on the VAS, rated on a scale of 1 to 10; 3) investigator's global assessment of disease on the VAS; 4) patient's assessment of disability on the health assessment questionnaire (HAQ), rated on a scale of 1 to 3; and 5) concentrations of acute phase reactants. For all scales (1-4): smaller values better. The ACR20 were evaluated descriptively. The data were analysed with a Bayesian approach using an informative prior for the placebo treatment group; predictive probability that the treatment difference was larger than 0%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40% or 45% was to be evaluated.
Measured: at week 12 (day 85) from the initiation of study treatment
Secondary outcomes (6)
Part 2: ACR50 Response Rates at Week 12
ACR 50 criteria at week 12 relative to the patient's status at baseline: that is, at least 50 % improvement in swollen joint count, at least 50% improvement in tender joint count, and at least 50% improvement in ≥3 of the following 5 variables: 1) patient's assessment of pain on the visual analogue scale (VAS), rated on a scale of 1 to 10; 2) patient's global assessment of disease on the VAS, rated on a scale of 1 to 10; 3) investigator's global assessment of disease on the VAS; 4) patient's assessment of disability on the health assessment questionnaire (HAQ), rated on a scale of 1 to 3; and 5) concentrations of acute phase reactants. For all scales (1-4): smaller values better. The percentage of subjects with ACR50 response is presented.
Measured: at week 12 (day 85)
Part 2: ACR70 Response Rates at Week 12
ACR70 criteria at week 12 relative to the patient's status at baseline: that is, at least 70 % improvement in swollen joint count, at least 70% improvement in tender joint count, and at least 70% improvement in ≥3 of the following 5 variables: 1) patient's assessment of pain on the visual analogue scale (VAS), rated on a scale of 1 to 10; 2) patient's global assessment of disease on the VAS, rated on a scale of 1 to 10; 3) investigator's global assessment of disease on the VAS; 4) patient's assessment of disability on the health assessment questionnaire (HAQ), rated on a scale of 1 to 3; and 5) concentrations of acute phase reactants. For all scales (1-4): smaller values better). The percentage of subjects with ACR50 response is presented.
Measured: at week 12 (day 85)
Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12
Assessed by European League Against Rheumatism (EULAR) categorization as good, moderate, or nonresponders based on improvement from baseline using the DAS28-CRP at week 12. In this outcome measure the frequency of EULAR response rates (change from the day of first dose to the day of visit 14 in week 12) are presented. DAS28-CRP is calculated as 0.56*√(TJC) + 0.28*√(SJC) + 0.36*Ln(CRP+1) + 0.014*VAS + 0.96. The total score ranges from 1.0 to 9.4, where a higher score indicates a better outcome.
EULAR response states were classified as follows:
good responders were patients with an improvement of >1.2 and a present score of ⩽3.2;
moderate responders were patients with an improvement of >0.6 to ⩽1.2 and a present score of ⩽5.1, or an improvement of >1.2 and a present score of >3.2;
non-responders were any patients with an improvement of ⩽0.6, or patients with an improvement of >0.6 to ⩽1.2 and a present score of >5.1.
Improvement (impr.) is abbreviated in the category names.
Measured: baseline (day 1) and week 12 (day 85)
Part 2: EULAR DAS28-ESR at Week 12
Response as assessed by European League Against Rheumatism (EULAR) using Disease activity score in 28 joints and the erythrocyte sedimentation rate (DAS28-ESR) at week 12. In this outcome measure the frequency of EULAR response rates (change from the day of first dose to the day of visit 14 in week 12) are presented. DAS28-ESR is calculated as 0.56*√(TJC) + 0.28*√(SJC) + 0.70 *Ln(ESR) + 0.014*VAS. The total score ranges from 0 to 9.4, where a higher score indicates a better outcome.
EULAR response states were classified as follows:
good responders were patients with an improvement of >1.2 and a present score of ⩽3.2;
moderate responders were patients with an improvement of >0.6 to ⩽1.2 and a present score of ⩽5.1, or an improvement of >1.2 and a present score of >3.2;
non-responders were any patients with an improvement of ⩽0.6, or patients with an improvement of >0.6 to ⩽1.2 and a present score of >5.1.
Improvement (impr.) is abbreviated in the category names.
Measured: baseline (day 1) and week 12 (day 85)
Part 2: Percentage of Patients With a Decrease in DAS28-CRP of >1.2 at Week 12
Percentage of patients who had a decrease of >1.2 on the Disease activity score in 28 joints and C-reactive protein (DAS28-CRP) at week 12 (day 85) compared to baseline. The adjusted absolute risk difference was adjusted for treatment, region and anti-TNF history. DAS28-CRP is calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst), where the total score is calculated as follows: 0.56*√(TJC) + 0.28*√(SJC) + 0.36*Ln(CRP+1) + 0.014*VAS + 0.96. The total score ranges from 1.0 to 9.4, where a higher score indicates a better outcome.
Measured: baseline (day 1) and week 12 (day 85)
Part 2: Change in DAS28-CRP Score at Week 12
Change at week 12 in the Disease activity score in 28 joints and C-reactive protein (DAS28-CRP) compared with the score at baseline. The mean was adjusted for region, anti-TNF history and baseline DAS28-CRP. DAS28-CRP is calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst), where the total score is calculated as follows: 0.56*√(TJC) + 0.28*√(SJC) + 0.36*Ln(CRP+1) + 0.014*VAS + 0.96. The total score ranges from 1.0 to 9.4, where a higher score indicates a better outcome.
Measured: baseline (day 1) and week 12 (day 85)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2012 (estimated)
- Study start18 Dec 2012
- Primary completion2 Mar 2015
- Study completion27 Apr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Arthritis, RheumatoidStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01751776
- Sponsor's protocol ID
- 1293.2
- Other IDs
- 2012-004090-16
- Status last verified
- Sep 2023
- First submitted
- 14 Dec 2012
- Last updated
- 21 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Visvanathan S, Daniluk S, Ptaszynski R, Muller-Ladner U, Ramanujam M, Rosenstock B, Eleftheraki AG, Vinisko R, Petrikova A, Kellner H, Dokoupilova E, Kwiatkowska B, Alten R, Schwabe C, Baum P, Joseph D, Fine JS, Padula SJ, Steffgen J. Effects of BI 655064, an antagonistic anti-CD40 antibody, on clinical and biomarker variables in patients with active rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase IIa study. Ann Rheum Dis. 2019 Jun;78(6):754-760. doi: 10.1136/annrheumdis-2018-214729. Epub 2019 Mar 22.
PubMed 30902820
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01751776
- Acronym / sponsor ID
- 1293.2
- Conditions
- Arthritis, Rheumatoid, Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 107 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 18 Dec 2012 (actual)
- Primary completion
- 2 Mar 2015 (actual)
- Study completion
- 27 Apr 2015 (actual)
- First posted
- 18 Dec 2012 (estimated)
- Results
- Posted 21 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Part 1, Placebo BI 655064 80/120mg (HV) | Placebo comparator | Drug: Placebo matching BI 655064Part 1, Healthy volunteers (HV): Placebo matching BI 655064 80 or 120 milligram (mg) injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. |
| Part 1, Placebo BI 655064 180/240mg (HV) | Placebo comparator | Drug: Placebo matching BI 655064Part 1, Healthy volunteers (HV): Placebo matching BI 655064 180 or 240 mg injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks (180mg dosing group) or 8 weeks (240mg dosing group) follow-up period. |
| Part 1, BI 655064 80mg (HV) | Experimental | Drug: BI 655064Part 1, Healthy volunteers (HV): 80 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. |
| Part 1, BI 655064 120mg (HV) | Experimental | Drug: BI 655064Part 1, Healthy volunteers (HV): 120 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. |
| Part 1, BI 655064 180mg (HV) | Experimental | Drug: BI 655064Part 1, Healthy volunteers (HV): 180 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. |
| Part 1, BI 655064 240mg (HV) | Experimental | Drug: BI 655064Part 1, Healthy volunteers (HV): 240mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 8 weeks follow-up period. |
| Part 2, Placebo BI 655064 120mg (RA) | Placebo comparator | Drug: Placebo matching BI 655064Part 2, patients with Rheumatoid arthritis (RA) who had prior inadequate response to Methotrexat (MTX) therapy: Placebo matching BI 655064 120 milligram (mg) injected subcutaneous on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (once weekly for 12 weeks) followed by 8 weeks follow-up period. |
| Part 2, BI 655064 120mg (RA) | Experimental | Drug: BI 655064Part 2, patients with RA who had prior inadequate response to MTX therapy: 120 milligram (mg) of BI 655064 injected subcutaneous on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (once weekly for 12 weeks) followed by 8 weeks follow-up period. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- 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
- Age >= 18 and <= 60 years
- Body Mass Index >= 18.5 and <= 29.9 kg/m2
- Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation
- 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:
Key exclusion criteria (23 listed)
- Any finding in the medical examination (including BP, PR or ECG) deviating from normal and judged clinically relevant by the investigator
- Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
- Any evidence of a concomitant disease judged clinically relevant by the investigator
- Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- Diseases of the central nervous system (such as epilepsy), other neurological disorders or psychiatric disorders
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo matching BI 655064Placebo matching BI 655064 injected subcutaneous. | Drug | Part 1, Placebo BI 655064 180/240mg (HV), Part 1, Placebo BI 655064 80/120mg (HV), Part 2, Placebo BI 655064 120mg (RA) |
| BI 655064BI 655064 injected subcutaneous | Drug | Part 1, BI 655064 120mg (HV), Part 1, BI 655064 180mg (HV), Part 1, BI 655064 240mg (HV), Part 1, BI 655064 80mg (HV), Part 2, BI 655064 120mg (RA) |
Primary outcome
Part 1: Cmax After the First and Last Dose
Time frame: From first day of drug administration till end of trial, up to 77 days. Detailed PK can be found in the endpoint description.
Part 1: This outcome measure presents the maximum measured concentration of BI 655064 in plasma (Cmax) after the first and last (fourth) dose. More detailed time frame: Pharmacokinetic (PK) sample times: 0:30 hour (h) prior first administration of BI 655064 and 1 h, 8 h, 12 h, 24 h, 48 h, 72 h, 84 h, 96 h, 108 h, 120 h, 144 h, 167:30 h, 335:30 h, 503:30 h, 505 h, 516 h, 528 h, 552 h, 576 h, 600 h, 624 h, 648 h, 672 h, 696 h, 744 h, 816 h, 912 h, 1008 h, 1176 h, 1344 h, 1512 h, 1848 h thereafter; further administration times for BI 655064: 168 h, 336 h, and 504 h after first administration.
Part 1: AUC 0-infinity After the Last Dose
Time frame: PK sample times: 1 h, 12 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 192 h, 240 h, 312 h, 408 h, 504 h, 672 h, 840 h, 1008 h, 1344 h after the last administration of BI 655064 on day 22
Part 1: Area under the concentration-time curve of BI 655064 in plasma over the time interval from 0 extrapolated to infinite (AUC 0-infinity).
Part 1: AUCtau After the Last Dose
Time frame: PK sample times: 1 h, 12 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 192 h, 240 h, 312 h, 408 h, 504 h, 672 h, 840 h, 1008 h, 1344 h after the last administration of trial drug on day 22
Area under the concentration-time curve of BI 655064 in plasma after the 4th dose over a uniform dosing interval t (AUC t,4) after the first and 4th dose. AUCtau is synonymous with AUC0-168.
Part 1: Percentage of Subjects With Drug Related Adverse Events
Time frame: from first administration of study medication (day 1) up to day 64 (dosing groups 80, 120, 180mg) or up to day 78 post-treatment (dosing group 240mg)
In Part 1 (Phase Ib): The primary safety endpoint was the percentage of subjects with AEs related to treatment with trial medication.
Part 2: American College of Rheumatology (ACR)20 Response Rate at Week 12
Time frame: at week 12 (day 85) from the initiation of study treatment
ACR 20 criteria at week 12 relative to the patient's status at baseline: that is, at least 20 percent (%) improvement in swollen joint count, at least 20% improvement in tender joint count, and at least 20% improvement in ≥3 of the following 5 variables: 1) patient's assessment of pain on the visual analogue scale (VAS), rated on a scale of 1 to 10; 2) patient's global assessment of disease on the VAS, rated on a scale of 1 to 10; 3) investigator's global assessment of disease on the VAS; 4) patient's assessment of disability on the health assessment questionnaire (HAQ), rated on a scale of 1 to 3; and 5) concentrations of acute phase reactants. For all scales (1-4): smaller values better. The ACR20 were evaluated descriptively. The data were analysed with a Bayesian approach using an informative prior for the placebo treatment group; predictive probability that the treatment difference was larger than 0%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40% or 45% was to be evaluated.
6 secondary outcomes
Part 2: ACR50 Response Rates at Week 12
Time frame: at week 12 (day 85)
Part 2: ACR70 Response Rates at Week 12
Time frame: at week 12 (day 85)
Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12
Time frame: baseline (day 1) and week 12 (day 85)
Part 2: EULAR DAS28-ESR at Week 12
Time frame: baseline (day 1) and week 12 (day 85)
Part 2: Percentage of Patients With a Decrease in DAS28-CRP of >1.2 at Week 12
Time frame: baseline (day 1) and week 12 (day 85)
Part 2: Change in DAS28-CRP Score at Week 12
Time frame: baseline (day 1) and week 12 (day 85)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30902820Visvanathan S, Daniluk S, Ptaszynski R, Muller-Ladner U, Ramanujam M, Rosenstock B, Eleftheraki AG, Vinisko R, Petrikova A, Kellner H, Dokoupilova E, Kwiatkowska B, Alten R, Schwabe C, Baum P, Joseph D, Fine JS, Padula SJ, Steffgen J. Effects of BI 655064, an antagonistic anti-CD40 antibody, on clinical and biomarker variables in patients with active rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase IIa study. Ann Rheum Dis. 2019 Jun;78(6):754-760. doi: 10.1136/annrheumdis-2018-214729. Epub 2019 Mar 22.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
25 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BI 655064 in people with Arthritis, Rheumatoid and Healthy, run by Boehringer Ingelheim at 25 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in Poland, Germany, Spain, Netherlands, Czechia and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Cmax After the First and Last Dose (time frame: From first day of drug administration till end of trial, up to 77 days. Detailed PK can be found in the endpoint description.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01751776, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2024; AzTrials last refreshed its copy on 7 Nov 2026.