Rheumatoid ArthritisPhase 1NCT02675803
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of VAY736 in Rheumatoid Arthritis Patients
A Phase 1 study testing VAY736 in people with Rheumatoid Arthritis, run by Novartis Pharmaceuticals at 1 site in Germany.
Trial summary
This study investigated the safety and tolerability of VAY736 administered as single ascending doses of intravenous infusion, subcutaneous injection and repeated subcutaneous injections in rheumatoid arthritis patients. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- VAY736
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 1 siteGermany
- Study dates
- 20 Dec 2010to 22 Jan 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Active disease despite methotrexate treatment 5 to 20 mg/week for Parts 1 and 2; methotrexate treatment 5 to 20 mg/week for Part 3
- Fulfilled 2010 American College of Rheumatolody (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis for Part 1 and Part 2. For Part 3, fulfilled 2010 American College of Rheumatolody (ACR)/)/European League Against Rheumatism (EULAR) classification criteria or/and 1987 American College of Rheumatolody (ACR) classification criteria for rheumatoid arthritis;
- Methotrexate ≥ 16 weeks, stable dose ≥ 8 weeks
Who cannot join
- Previous treatment with a B cell-depleting biologic agent.
- Autoimmune disease other than RA except concurrent Sjogren's syndrome
- Adult juvenile rheumatoid arthritis
- ARA functional class IV disease of ACR Revised Steinbrocker Classification
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of VAY736 in Rheumatoid Arthritis Patients
This study investigated the safety and tolerability of VAY736 administered as single ascending doses of intravenous infusion, subcutaneous injection and repeated subcutaneous injections in rheumatoid arthritis patients.
Read the detailed description
This study had three sequential parts which investigated the safety and tolerability of VAY736 administered as single ascending doses of intravenous infusion (Part 1), single ascending doses of subcutaneous injection (Part 2), and repeated subcutaneous injections of fixed doses (Part 3), respectively, in rheumatoid arthritis patients. Part 1 was double blind, placebo controlled, with 11 cohorts. Part 2 was open-label study with 2 dosing cohorts. Part 3 was open-label study with 1 fixed-dose cohort.
- Conditions
- Rheumatoid Arthritis
- Being tested
- VAY736, VAY736 placebo
- Keywords
- Rheumatoid arthritis
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VAY736Biological
VAY736 treatment
VAY736 placeboBiological
VAY736 placebo
| Study group | Role | What they receive |
|---|---|---|
| VAY736 | Experimental | VAY736 active Receives: Biological: VAY736 |
| Placebo | Placebo comparator | VAY736 placebo Receives: Biological: VAY736 placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability as measured by the number of patients wth adverse events
Part 1 The number of patients with adverse events after single intravenous (i.v.) dose of VAY736. Patients are assessed weekly up to 34 weeks post dose or until B cells reach the recovery criteria
Part 2 The number of patients with adverse events after single subcutaneous (s.c.) dose of VAY736. Patients are assessed weekly, bi-weekly, then every 4, 8 and 12 weeks up to 188 weeks post dose or until B cells reach the recovery criteria.
Part 3 The number of patients with adverse events after repeated subcutaneous (s.c) injections of a fixed dose of VAY736. Patients are assessed bi-weekly, then every 4 weeks and 8 weeks up to 27 weeks from the first dose.
Measured: 27-188 weeks
Absolute bioavailability of VAY736: The ratio of area under curve (AUC) for s.c dose and for intravenous dose
Part 2 The ratio of area under curve (AUC) for single s.c dose and intravenous dose is determined
Measured: 188 weeks
Plasma pharmacokinetics of VAY736: The area under the plasma concentration-time curve from time zero to the end of the dosing interval (AUCtau)
In Part 3:
After the first and last s.c. doses, the area under the plasma concentration-time curve from time zero to the end of the dosing interval (AUCtau) will be determined
Measured: 27 weeks
Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)
In Part 3:
After the first and last s.c. doses, the Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) will be determined.
Measured: 27 weeks
Plasma pharmacokinetics of VAY736: Observed maximum plasma concentration following drug administration (Cmax)
In Part 3:
After the first and last s.c. doses, the Observed maximum plasma concentration following drug administration (Cmax) will be determined
Measured: 27 weeks
Plasma pharmacokinetics of VAY736: Time to reach the maximum concentration after drug administration (Tmax)
In Part 3:
After the first and last s.c. doses, the time to reach the maximum concentration after drug administration (Tmax) will be determined
Measured: 27 weeks
Plasma pharmacokinetics of VAY736: The terminal elimination half-life (T1/2)
In Part 3:
After the first and last s.c. doses, the terminal elimination half-life (T1/2) will be determined
Measured: 27 weeks
Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to infinity (AUCinf)
In Part 3:
After the first and last s.c. doses, Area under the plasma concentration-time curve from time zero to infinity (AUCinf) will be determined.
Measured: 27 weeks
Plasma pharmacokinetics of VAY736: concentration of VAY736 during the treatment period, before each dose (Ctrough)
In Part 3:
After the first and last s.c. doses, the concentration of VAY736 during the treatment period, before each dose (Ctrough) will be determined
Measured: 27 weeks
Safety and tolerability as measured by the percentage of patients wth adverse events
Part 1 The percentage of patients with adverse events after single intravenous (i.v.) dose of VAY736. Patients are assessed weekly up to 34 weeks post dose or until B cells reach recovery criteria.
Part 2 The percentage of patients with adverse events after single subcutaneous (s.c.) dose of VAY736. Patients are assessed weekly, bi-weekly, then every 4, 8 and 12 weeks up to 68 weeks post dose or until B cells reach recovery criteria..
Part 3 The percentage of patients with adverse events after repeated subcutaneous (s.c) injections of a fixed dose of VAY736. Patients are assessed bi-weekly, then every 4 weeks and 8 weeks up to 27 weeks from the first dose.
Measured: 27-188 weeks
Secondary outcomes (7)
pharmacodynamics of VAY736
B cell depletion/recovery after single i.v. dose of VAY736, single s.c. dose of VAY736 and multiple fixed s.c. doses of VAY736 administration in the 3 parts of the study
Measured: 27-188 weeks
Immunogenicity of VAY736
Immunogenicity after administration of single i.v. dose of VAY736, single s.c. dose of VAY736 and multiple fixed s.c. doses of VAY736 in 3 parts of the study.
Measured: 27-188 weeks
Plasma bioavailability of VAY736: The ratio of area under curve (AUC) for repeated s.c doses and for intravenous dose
Part 3 The ratio of area under curve (AUC) for repeated s.c doses and for intravenous dose is determined
Measured: 27 weeks
Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)
The area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) will be determined after single i.v. dose and s.c. dose of VAY736 in Part 1 and Part 2 respectively
Measured: 34-188 weeks
Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to infinity (AUCinf)
The area under the plasma concentration-time curve from time zero to infinity (AUCinf) will be determined after single i.v. dose and s.c. dose of VAY736 in Part 1 and Part 2 respectively.
Measured: 34-188 weeks
Plasma pharmacokinetics of VAY736: Observed maximum plasma concentration following drug Administration (Cmax)
The Observed maximum plasma concentration following drug administration (Cmax) will be determined after single i.v. dose and s.c. dose of VAY736 in Part 1 and Part 2 respectively
Measured: 34-188 weeks
Plasma pharmacokinetics of VAY736: Time to reach the maximum concentration after drug administration (Tmax)
The time to reach the maximum concentration after drug administration (Tmax) will be determined after single i.v. dose and s.c. dose of VAY736 in Part 1 and Part 2 respectively
Measured: 34-188 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2016 (estimated)
- Study start20 Dec 2010
- Primary completion22 Jan 2018
- Study completion22 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02675803
- Sponsor's protocol ID
- CVAY736X2101
- Other IDs
- 2010-020156-65
- Status last verified
- Jan 2019
- First submitted
- 9 Jul 2015
- Last updated
- 11 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of VAY736 in Rheumatoid Arthritis Patients
- ClinicalTrials.gov ID
- NCT02675803
- Acronym / sponsor ID
- CVAY736X2101
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid arthritis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 20 Dec 2010 (actual)
- Primary completion
- 22 Jan 2018 (actual)
- Study completion
- 22 Jan 2018 (actual)
- First posted
- 5 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study investigated the safety and tolerability of VAY736 administered as single ascending doses of intravenous infusion, subcutaneous injection and repeated subcutaneous injections in rheumatoid arthritis patients.
Detailed description
This study had three sequential parts which investigated the safety and tolerability of VAY736 administered as single ascending doses of intravenous infusion (Part 1), single ascending doses of subcutaneous injection (Part 2), and repeated subcutaneous injections of fixed doses (Part 3), respectively, in rheumatoid arthritis patients. Part 1 was double blind, placebo controlled, with 11 cohorts. Part 2 was open-label study with 2 dosing cohorts. Part 3 was open-label study with 1 fixed-dose cohort.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| VAY736 | Experimental | Biological: VAY736VAY736 active |
| Placebo | Placebo comparator | Biological: VAY736 placeboVAY736 placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Active disease despite methotrexate treatment 5 to 20 mg/week for Parts 1 and 2; methotrexate treatment 5 to 20 mg/week for Part 3
- Fulfilled 2010 American College of Rheumatolody (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis for Part 1 and Part 2. For Part 3, fulfilled 2010 American College of Rheumatolody (ACR)/)/European League Against Rheumatism (EULAR) classification criteria or/and 1987 American College of Rheumatolody (ACR) classification criteria for rheumatoid arthritis;
- Methotrexate ≥ 16 weeks, stable dose ≥ 8 weeks
Key exclusion criteria (4 listed)
- Previous treatment with a B cell-depleting biologic agent.
- Autoimmune disease other than RA except concurrent Sjogren's syndrome
- Adult juvenile rheumatoid arthritis
- ARA functional class IV disease of ACR Revised Steinbrocker Classification
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 |
|---|---|---|
| VAY736VAY736 treatment | Biological | VAY736 |
| VAY736 placeboVAY736 placebo | Biological | Placebo |
Primary outcome
Safety and tolerability as measured by the number of patients wth adverse events
Time frame: 27-188 weeks
Part 1 The number of patients with adverse events after single intravenous (i.v.) dose of VAY736. Patients are assessed weekly up to 34 weeks post dose or until B cells reach the recovery criteria Part 2 The number of patients with adverse events after single subcutaneous (s.c.) dose of VAY736. Patients are assessed weekly, bi-weekly, then every 4, 8 and 12 weeks up to 188 weeks post dose or until B cells reach the recovery criteria. Part 3 The number of patients with adverse events after repeated subcutaneous (s.c) injections of a fixed dose of VAY736. Patients are assessed bi-weekly, then every 4 weeks and 8 weeks up to 27 weeks from the first dose.
Absolute bioavailability of VAY736: The ratio of area under curve (AUC) for s.c dose and for intravenous dose
Time frame: 188 weeks
Part 2 The ratio of area under curve (AUC) for single s.c dose and intravenous dose is determined
Plasma pharmacokinetics of VAY736: The area under the plasma concentration-time curve from time zero to the end of the dosing interval (AUCtau)
Time frame: 27 weeks
In Part 3: After the first and last s.c. doses, the area under the plasma concentration-time curve from time zero to the end of the dosing interval (AUCtau) will be determined
Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)
Time frame: 27 weeks
In Part 3: After the first and last s.c. doses, the Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) will be determined.
Plasma pharmacokinetics of VAY736: Observed maximum plasma concentration following drug administration (Cmax)
Time frame: 27 weeks
In Part 3: After the first and last s.c. doses, the Observed maximum plasma concentration following drug administration (Cmax) will be determined
Plasma pharmacokinetics of VAY736: Time to reach the maximum concentration after drug administration (Tmax)
Time frame: 27 weeks
In Part 3: After the first and last s.c. doses, the time to reach the maximum concentration after drug administration (Tmax) will be determined
Plasma pharmacokinetics of VAY736: The terminal elimination half-life (T1/2)
Time frame: 27 weeks
In Part 3: After the first and last s.c. doses, the terminal elimination half-life (T1/2) will be determined
Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to infinity (AUCinf)
Time frame: 27 weeks
In Part 3: After the first and last s.c. doses, Area under the plasma concentration-time curve from time zero to infinity (AUCinf) will be determined.
Plasma pharmacokinetics of VAY736: concentration of VAY736 during the treatment period, before each dose (Ctrough)
Time frame: 27 weeks
In Part 3: After the first and last s.c. doses, the concentration of VAY736 during the treatment period, before each dose (Ctrough) will be determined
Safety and tolerability as measured by the percentage of patients wth adverse events
Time frame: 27-188 weeks
Part 1 The percentage of patients with adverse events after single intravenous (i.v.) dose of VAY736. Patients are assessed weekly up to 34 weeks post dose or until B cells reach recovery criteria. Part 2 The percentage of patients with adverse events after single subcutaneous (s.c.) dose of VAY736. Patients are assessed weekly, bi-weekly, then every 4, 8 and 12 weeks up to 68 weeks post dose or until B cells reach recovery criteria.. Part 3 The percentage of patients with adverse events after repeated subcutaneous (s.c) injections of a fixed dose of VAY736. Patients are assessed bi-weekly, then every 4 weeks and 8 weeks up to 27 weeks from the first dose.
7 secondary outcomes
pharmacodynamics of VAY736
Time frame: 27-188 weeks
Immunogenicity of VAY736
Time frame: 27-188 weeks
Plasma bioavailability of VAY736: The ratio of area under curve (AUC) for repeated s.c doses and for intravenous dose
Time frame: 27 weeks
Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)
Time frame: 34-188 weeks
Plasma pharmacokinetics of VAY736: Area under the plasma concentration-time curve from time zero to infinity (AUCinf)
Time frame: 34-188 weeks
Plasma pharmacokinetics of VAY736: Observed maximum plasma concentration following drug Administration (Cmax)
Time frame: 34-188 weeks
Plasma pharmacokinetics of VAY736: Time to reach the maximum concentration after drug administration (Tmax)
Time frame: 34-188 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2020.
- Results for CVAY736X2101 from the Novartis Clinical Trials WebsiteLink provided by the sponsor.
- A Plain Language Trial Summary is available on novartisclinicatrials.comLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VAY736 in people with Rheumatoid Arthritis, run by Novartis Pharmaceuticals at 1 site in Germany.
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 3 inclusion and 4 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 11 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety and tolerability as measured by the number of patients wth adverse events (time frame: 27-188 weeks). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Dec 2020.