Rheumatoid ArthritisPhase 1NCT02171143
A Dose Escalation Study to Assess Safety, Tolerability and Pharmacokinetics of ASP2409 Following a Single Intravenous Dose in Patients With Rheumatoid Arthritis on Methotrexate
A Phase 1 study testing ASP2409 in people with Rheumatoid Arthritis and Pharmacokinetics of ASP2409, run by Astellas Pharma Global Development, Inc. at 10 sites in United States.
Trial summary
The purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of single, ascending, intravenous (IV) doses of ASP2409 in patients with Rheumatoid Arthritis (RA) on methotrexate (MTX) and to evaluate the pharmacodynamics (PD) of ASP2409. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rheumatoid Arthritis, Pharmacokinetics of ASP2409
- What is being tested?
- ASP2409
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 58 participants
- Where
- 10 sitesUnited States
- Study dates
- Apr 2012to Apr 2014
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject weighs at least 50 kg.
- Subject has a body mass index (BMI) of ≤ 35 kg/m2.
- Subject's 12-lead electrocardiogram (ECG) results are normal at Screening and Day -1 or, if abnormal, the abnormality is not clinically significant
- Female subject must be either:
- Of non-childbearing potential:
- post-menopausal (defined as at least 1 year without any menses) prior to Screening, or
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- documented surgically sterile or status post hysterectomy (at least 1 month prior to Screening).
- Or, if of childbearing potential:
- must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -1.
- must use two forms of birth control (at least one of which must be a barrier method) starting at Screening and throughout the Treatment and Observation Period, and for ≥ 120 days after final study drug administration.
- Acceptable forms include:
- Established use or oral, injected or implanted hormonal methods of contraception.
- Placement of an intrauterine device (IUD) or intrauterine system (IUS).
- Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault cap) with spermicidal foam/gel/film/ cream/suppository.
- Female subject must not be breastfeeding at Screening or during the Treatment and Observation period and for ≥ 120 days after final study drug administration.
- Female subject must not donate ova starting at Screening and throughout the Treatment and Observation period and for ≥ 120 days after final study drug administration.
- Male subject must not donate sperm starting at Screening and throughout the Treatment and Observation period and for at least ≥ 120 days after final study drug administration.
- Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting at Screening and continue throughout the Treatment and Observation period and for ≥ 120 days after final study drug administration.
- Subject has Rheumatoid Arthritis (RA) that was diagnosed according to the 1987 revised criteria of the American College of Rheumatology (ACR) ≥ 6 months prior to Screening.
- Subject meets the ACR 1991 revised criteria for Global Functional Status in RA, Class I, II or III at Screening.
- Subject MUST be on concomitant methotrexate (MTX):
- for ≥ 3 months prior to study drug infusion, AND
- at a stable dose (10 - 25 mg/week) for ≥ 28 days prior to study drug infusion and throughout the study.
- Subjects on the following medications must remain on a stable regimen: non-steroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, hydroxychloroquine (Plaquenil®), sulfasalazine, oral corticosteroids (≤ 10 mg of prednisone, or equivalent, daily) or low dose opioids (≤ 30 mg of oral morphine, or equivalent, daily) for
- ≥ 28 days prior to Screening and remain so throughout the Treatment and Observation Period. (The start of Plaquenil and sulfasalazine must be ≥ 2 months prior to study drug infusion.)
- Subject is highly likely to comply with the protocol and complete the study.
Who cannot join
- Subject has an ongoing clinically significant systemic disease such as uncompensated heart failure, uncontrolled diabetes mellitus, severe hepatic failure or severe pulmonary disease.
- Subject has a history of any malignancy except for adequately-treated, non-melanoma skin cancer and adequately-treated in-situ cervical cancer.
- Subject has a history of severe allergic or anaphylactic reactions.
- Subject has a history of consuming more than 14 units of alcoholic beverages per week or has a history of alcoholism or drug/chemical/substance abuse within past 6 months prior to Screening (Note: one unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits).
- Subject has a positive test for alcohol or drugs of abuse (excluding drugs prescribed to subject) at Screening or Day -1.
- Subject has/had a viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to Day -1.
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- Subject has a past history of serious opportunistic infection.
- Subject is known positive for human immunodeficiency virus (HIV) antibody.
- Subject has a positive tuberculosis (TB) skin test or Quantiferon Gold test at Screening.
- Subject has a positive test for hepatitis C antibody, or positive test for hepatitis B surface antigen (HBsAg), or positive hepatitis B core antibody at Screening.
- Subject's laboratory test results at Screening:
- alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), are ˃ 2 times the upper limit of normal, AND/OR
- are outside the normal limits and considered by the Investigator to be clinically significant with regard to the remaining per-protocol laboratory tests.
- Subject received any live or live attenuated vaccine within 30 days prior to study drug infusion.
- Subject received any systemic immunosuppressant agent, other than (MTX) or stable steroid regimen, within 2 months prior to study drug infusion.
- Subject has previously received any antibody or therapeutic biologic product within 56 days or 5 half-lives, whichever is longer, prior to study drug infusion.
- Subject has previously participated in any interventional clinical study or has received an experimental agent within 56 days or 5 half-lives, whichever is longer, prior to study drug infusion.
- Subject is participating in another clinical trial or has participated in another dose group of the current trial.
- Subject has had any significant blood loss, donated one unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to clinic admission on Day -1.
- Subject has taken Orencia® (abatacept), Nulojix® (belatacept) or any other CTLA4-Ig molecule.
- Subject has any other condition which precludes the subject's participation in the trial.
- Subject has a history of prolonged QT syndrome.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Pinnacle Research Group, LLC
Anniston, Alabama, 36027
Community Research
Cincinnati, Ohio, 45255
Clinical Research of West Florida, Inc.
Clearwater, Florida, 33765
West Coast Clinical Trials, LLC
Costa Mesa, California, 92626
Metroplex Clinical Research Center, LLC
Dallas, Texas, 75231
Altoona Center for Clinical Research
Duncansville, Pennsylvania, 16635
Riverside Clinical Research
Edgewater, Florida, 32132
Lynn Health Science Institute
Oklahoma City, Oklahoma, 73122
Carolina Phase 1 Research
Raleigh, North Carolina, 27612
Texas Arthritis Research Center
San Antonio, Texas, 78217
About this study
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of ASP2409 Following a Single Intravenous Dose in Patients With Rheumatoid Arthritis on Methotrexate
The purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of single, ascending, intravenous (IV) doses of ASP2409 in patients with Rheumatoid Arthritis (RA) on methotrexate (MTX) and to evaluate the pharmacodynamics (PD) of ASP2409.
Read the detailed description
This is a dose-escalation study. Sequential cohorts of subjects will receive increasing doses of ASP2409 or matching placebo.
Subjects in all cohorts will stay confined in the unit for 3 days. All subjects will have scheduled outpatient visits and be followed for a minimum of 90 days.
- Conditions
- Rheumatoid Arthritis, Pharmacokinetics of ASP2409
- Being tested
- ASP2409, Placebo
- Keywords
- ASP2409, Rheumatoid Arthritis, methotrexate
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASP2409Drug
intravenous (IV)
PlaceboDrug
intravenous (IV)
| Study group | Role | What they receive |
|---|---|---|
| ASP2409 Dose Escalation | Experimental | Not described Receives: Drug: ASP2409 |
| Placebo Dose Escalation | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics of ASP2409 concentration: Area under the concentration - time curve from time 0 up to the last quantifiable concentration (AUClast)
Measured: Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120
Pharmacokinetics of ASP2409 concentration: Area under the concentration - time curve from time 0 extrapolated to infinity (AUCinf)
Measured: Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120
Pharmacokinetics of ASP2409 concentration: Maximum concentration (Cmax)
Measured: Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120
Safety assessed by adverse events
Measured: Up to 1 year
Safety assessed by laboratory tests
Measured: Up to 1 year
Safety assessed by electrocardiograms (ECGs)
Measured: Up to 1 year
Safety assessed by physical examinations
Measured: Up to 1 year
Safety assessed by vital signs
Measured: Up to 1 year
Safety assessed by anti-ASP2409 antibody formation
Measured: Up to 1 year
Secondary outcomes (2)
Composite of pharmacokinetics of ASP2409 concentration: tmax, t1/2, Vz, Vss, CLtot
Time to attain Cmax (tmax), apparent terminal elimination half-life (t1/2), terminal phase volume (Vz), volume of distribution at steady-state (Vss), and total body clearance (CLtot)
Measured: Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120
Pharmacodynamics of ASP2409: CD86 receptor occupancy
Cluster of Differentiation 86 (CD86), a co-stimulatory ligand on lymphocytes
Measured: Days 1-3, Days 5, 8, 15, 22, 29, 43, 60, and 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2014 (estimated)
- Study startApr 2012
- Primary completionApr 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Astellas Pharma Global Development, Inc.The 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Global Development, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Senior Medical Director, Study director, Astellas Pharma Global Development, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02171143
- Sponsor's protocol ID
- 2409-CL-0104
- Status last verified
- Jun 2014
- First submitted
- 18 Jun 2014
- Last updated
- 24 Jun 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Zhang W, Kernstock RM, Karrer EE, Cohen SB, Chindalore VL, Kivitz AJ, Blahunka PC, Delgado-Herrera L, Zeiher BG, Samberg NL, Garg JP. A Phase 1 Dose-Escalation Study of ASP2409, a Selective T-Cell Costimulation Inhibitor, in Stable Rheumatoid Arthritis Patients on Methotrexate Therapy. Clin Pharmacol Drug Dev. 2016 Jul;5(4):259-68. doi: 10.1002/cpdd.237. Epub 2016 Jan 8.
PubMed 27310327
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of ASP2409 Following a Single Intravenous Dose in Patients With Rheumatoid Arthritis on Methotrexate
- ClinicalTrials.gov ID
- NCT02171143
- Acronym / sponsor ID
- 2409-CL-0104
- Conditions
- Rheumatoid Arthritis, Pharmacokinetics of ASP2409
- Keywords
- ASP2409, Rheumatoid Arthritis, methotrexate
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Astellas Pharma Global Development, Inc.Industry (pharma, biotech, devices)
- Study start
- Apr 2012
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 24 Jun 2014 (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.
The purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of single, ascending, intravenous (IV) doses of ASP2409 in patients with Rheumatoid Arthritis (RA) on methotrexate (MTX) and to evaluate the pharmacodynamics (PD) of ASP2409.
Detailed description
This is a dose-escalation study. Sequential cohorts of subjects will receive increasing doses of ASP2409 or matching placebo.
Subjects in all cohorts will stay confined in the unit for 3 days. All subjects will have scheduled outpatient visits and be followed for a minimum of 90 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ASP2409 Dose Escalation | Experimental | Drug: ASP2409 |
| Placebo Dose Escalation | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Subject weighs at least 50 kg.
- Subject has a body mass index (BMI) of ≤ 35 kg/m2.
- Subject's 12-lead electrocardiogram (ECG) results are normal at Screening and Day -1 or, if abnormal, the abnormality is not clinically significant
- Female subject must be either:
- Female subject must not be breastfeeding at Screening or during the Treatment and Observation period and for ≥ 120 days after final study drug administration.
Key exclusion criteria (22 listed)
- Subject has an ongoing clinically significant systemic disease such as uncompensated heart failure, uncontrolled diabetes mellitus, severe hepatic failure or severe pulmonary disease.
- Subject has a history of any malignancy except for adequately-treated, non-melanoma skin cancer and adequately-treated in-situ cervical cancer.
- Subject has a history of severe allergic or anaphylactic reactions.
- Subject has a history of consuming more than 14 units of alcoholic beverages per week or has a history of alcoholism or drug/chemical/substance abuse within past 6 months prior to Screening (Note: one unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits).
- Subject has a positive test for alcohol or drugs of abuse (excluding drugs prescribed to subject) at Screening or Day -1.
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 |
|---|---|---|
| ASP2409intravenous (IV) | Drug | ASP2409 Dose Escalation |
| Placebointravenous (IV) | Drug | Placebo Dose Escalation |
Primary outcome
Pharmacokinetics of ASP2409 concentration: Area under the concentration - time curve from time 0 up to the last quantifiable concentration (AUClast)
Time frame: Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120
Pharmacokinetics of ASP2409 concentration: Area under the concentration - time curve from time 0 extrapolated to infinity (AUCinf)
Time frame: Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120
Pharmacokinetics of ASP2409 concentration: Maximum concentration (Cmax)
Time frame: Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120
Safety assessed by adverse events
Time frame: Up to 1 year
Safety assessed by laboratory tests
Time frame: Up to 1 year
Safety assessed by electrocardiograms (ECGs)
Time frame: Up to 1 year
Safety assessed by physical examinations
Time frame: Up to 1 year
Safety assessed by vital signs
Time frame: Up to 1 year
Safety assessed by anti-ASP2409 antibody formation
Time frame: Up to 1 year
2 secondary outcomes
Composite of pharmacokinetics of ASP2409 concentration: tmax, t1/2, Vz, Vss, CLtot
Time frame: Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120
Pharmacodynamics of ASP2409: CD86 receptor occupancy
Time frame: Days 1-3, Days 5, 8, 15, 22, 29, 43, 60, and 90
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 24 Jun 2014.
- Derived from this study: PubMed 27310327Zhang W, Kernstock RM, Karrer EE, Cohen SB, Chindalore VL, Kivitz AJ, Blahunka PC, Delgado-Herrera L, Zeiher BG, Samberg NL, Garg JP. A Phase 1 Dose-Escalation Study of ASP2409, a Selective T-Cell Costimulation Inhibitor, in Stable Rheumatoid Arthritis Patients on Methotrexate Therapy. Clin Pharmacol Drug Dev. 2016 Jul;5(4):259-68. doi: 10.1002/cpdd.237. Epub 2016 Jan 8.
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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.
Senior Medical Director study director
Astellas Pharma Global Development, Inc.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ASP2409 in people with Rheumatoid Arthritis and Pharmacokinetics of ASP2409, run by Astellas Pharma Global Development, Inc. at 10 sites in United States.
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 26 inclusion and 22 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 24 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. 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?
Pharmacokinetics of ASP2409 concentration: Area under the concentration - time curve from time 0 up to the last quantifiable concentration (AUClast) (time frame: Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120). The study lists 9 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 NCT02171143, 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 24 Jun 2014.