Rheumatoid ArthritisPhase 2August IIINCT00664521
Atacicept in Combination With Rituximab in Subjects With Rheumatoid Arthritis (August III)
A Phase 2 study testing Rituximab and Atacicept in people with Rheumatoid Arthritis, run by Merck KGaA, Darmstadt, Germany at 8 sites in 4 countries.
Trial summary
The primary objective of this study is to assess the safety and tolerability of combined treatment with atacicept and rituximab in subjects with active rheumatoid arthritis (RA) receiving re-treatment with rituximab. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Rituximab and Atacicept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 8 sitesin 4 countries
- Study dates
- Mar 2008to Oct 2010
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female subjects
- Greater than and equal to (>=) 18 years of age at the time of Informed Consent
- Who have rheumatoid arthritis satisfying American College of Rheumatology (ACR) criteria with a disease history of at least 12 months
- Subjects must have active disease defined by DAS28 >3.2
- Subjects must have received previous treatment with rituximab and must be candidates for re-treatment with rituximab
- Female subjects of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for 4 weeks before study day 1 (SD1), during the treatment period and for 12 months after the last dose of rituximab, and must have a negative urine pregnancy test at the screening visit and SD1
- Other protocol defined inclusion criteria could apply
Who cannot join
- Current neurological disease excluding migraine
- Inflammatory joint disease other than rheumatoid arthritis
- Any contraindication to rituximab as per national label
- Use of disease-modifying anti-rheumatic drugs (DMARDs; including methotrexate) for less than 3 months or change in dosing regimen within 28 days before SD1, or methotrexate dose regimen >25 mg/week
- Participation in any interventional clinical trial within 1 month before SD1 (or within 5 half-lives of the investigated compound before SD1, whichever is longer)
- Prednisone dose regimen >10 mg/day (or equivalent), or change in steroid dosing regimen within 28 days before SD1
Show all 12Show fewer
- Active or latent tuberculosis within the year before screening or major infection requiring hospitalization or intravenous anti-infectives within 28 days before SD1
- Serum Immunoglobulin G (IgG) below 6 gram per liter (g/L)
- Known hypersensitivity to atacicept or to any of the components of the formulated atacicpet
- Known hypersensitivity to rituximab, to any of the components of the formulated rituximab or to murine proteins
- Breastfeeding or pregnancy
- Other protocol defined exclusion criteria could apply
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
About this study
Official title: A Randomized, Double-blind, Placebo Controlled, Multi-centre, Exploratory, Pilot, Phase II Trial of 150mg Atacicept Given Subcutaneously in Combination With Rituximab in Subjects With Rheumatoid Arthritis.
The primary objective of this study is to assess the safety and tolerability of combined treatment with atacicept and rituximab in subjects with active rheumatoid arthritis (RA) receiving re-treatment with rituximab.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Rituximab, Atacicept, Placebo matched to atacicept
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabBiological
Rituximab will be administered as an intravenous infusion at a dose of 1000 mg at Weeks 1 and 3.
AtaciceptDrug
Atacicept will be administered at a dose of 150 mg subcutaneously once a week from Week 7 to 32.
Placebo matched to ataciceptDrug
Placebo matched to atacicept will be administered subcutaneously once a week from Week 7 to 32.
| Study group | Role | What they receive |
|---|---|---|
| Rituximab Plus Atacicept | Experimental | Rituximab will be administered as an intravenous infusion at a dose of 1000 mg at Weeks 1 and 3, followed by atacicept 150 mg subcutaneously once a week from Week 7 to 32. Receives: Biological: Rituximab; Drug: Atacicept |
| Rituximab Plus Placebo | Placebo comparator | Rituximab will be administered as an intravenous infusion at a dose of 1000 mg at Weeks 1 and 3, followed by placebo matched to atacicept subcutaneously once a week from Week 7 to 32. Receives: Biological: Rituximab; Drug: Placebo matched to atacicept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Measured: Baseline up to Week 64
Percentage of Participants With Immunoglobulin G (IgG) Level Less Than 3 Gram Per Liter (g/L)
Measured: Week 64
Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32
Vital signs assessed included blood pressure (systolic and diastolic), pulse and body temperature. Routine safety lab parameters evaluated included red blood cell (RBC), hemoglobin, hematocrit, platelets, mean cellular hemoglobin (MCH), MCH concentration, MCH volume, white blood cell (WBC), lymphocytes, monocytes, eosinophils, basophils, neutrophils, gamma glutamyl transferase (GGT), alanine aminotransferase (ALT), albumin, alkaline phosphatase (AP), aspartate aminotransferase (AST), bilirubin, calcium, creatinine, glucose, potassium, total protein, sodium, uric acid, and blood urea nitrogen. Percent change from baseline was calculated as ([Week 32 value minus baseline value] multiplied by 100) divided by baseline value.
Measured: Baseline, Week 32
Percent Change From Baseline in Anti-tetanus and Anti-diphteria Immunization Titer at Week 32
Percent change from baseline was calculated as ([Week 32 value minus baseline value] multiplied by 100) divided by baseline value.
Measured: Baseline, Week 32
Percent Change From Baseline in Anti-pneumococcus Titer at Week 32
Percent change from baseline was calculated as ([Week 32 value minus baseline value] multiplied by 100) divided by baseline value.
Measured: Baseline, Week 32
Secondary outcomes (3)
Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP), ACR50-CRP and ACR70-CRP at Week 32
ACR20-CRP response: greater than or equal to (>=) 20 percent (%) improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=20% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP). ACR50-CRP and ACR70-CRP response are defined as >=50% and >=70% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) respectively together with >=50% and >=70% improvement in at least 3 of the following respectively: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) CRP.
Measured: Week 32
Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) at Week 32
DAS28-CRP incorporates non-graded joint counts for tenderness and swelling based on a total of 28 joints, CRP as a marker of inflammation, and a general health assessment using a 100 mm visual analog scale (the participant's global assessment of disease activity). DAS28 score ranges between 0 and 10 representing current disease activity. A value above 5.1 represents high disease activity, a value below 3.2 represents low disease activity, and a value below 2.6 represents remission.
Measured: Baseline, Week 32
Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells
Flow cytometric analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of total, mature and memory B cell levels.
Measured: Baseline, Week 3, 7, 12, 16, 26 and 32
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2008 (estimated)
- Study startMar 2008
- Primary completionOct 2010
- Study completionOct 2010
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 Rheumatoid ArthritisStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00664521
- Sponsor's protocol ID
- 28155
- Acronym
- August III
- Status last verified
- Nov 2016
- First submitted
- 21 Apr 2008
- Last updated
- 30 Dec 2016
- Results posted
- Yes, on ClinicalTrials.gov
Publications
van Vollenhoven RF, Wax S, Li Y, Tak PP. Safety and efficacy of atacicept in combination with rituximab for reducing the signs and symptoms of rheumatoid arthritis: a phase II, randomized, double-blind, placebo-controlled pilot trial. Arthritis Rheumatol. 2015 Nov;67(11):2828-36. doi: 10.1002/art.39262.
PubMed 26137975
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo Controlled, Multi-centre, Exploratory, Pilot, Phase II Trial of 150mg Atacicept Given Subcutaneously in Combination With Rituximab in Subjects With Rheumatoid Arthritis.
- ClinicalTrials.gov ID
- NCT00664521
- Acronym / sponsor ID
- August III / 28155
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- Mar 2008
- Primary completion
- Oct 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 23 Apr 2008 (estimated)
- Results
- Posted 30 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to assess the safety and tolerability of combined treatment with atacicept and rituximab in subjects with active rheumatoid arthritis (RA) receiving re-treatment with rituximab.
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 |
|---|---|---|
| Rituximab Plus Atacicept | Experimental | Biological: Rituximab, Drug: AtaciceptRituximab will be administered as an intravenous infusion at a dose of 1000 mg at Weeks 1 and 3, followed by atacicept 150 mg subcutaneously once a week from Week 7 to 32. |
| Rituximab Plus Placebo | Placebo comparator | Biological: Rituximab, Drug: Placebo matched to ataciceptRituximab will be administered as an intravenous infusion at a dose of 1000 mg at Weeks 1 and 3, followed by placebo matched to atacicept subcutaneously once a week from Week 7 to 32. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male and female subjects
- Greater than and equal to (>=) 18 years of age at the time of Informed Consent
- Who have rheumatoid arthritis satisfying American College of Rheumatology (ACR) criteria with a disease history of at least 12 months
- Subjects must have active disease defined by DAS28 >3.2
- Subjects must have received previous treatment with rituximab and must be candidates for re-treatment with rituximab
Key exclusion criteria (12 listed)
- Current neurological disease excluding migraine
- Inflammatory joint disease other than rheumatoid arthritis
- Any contraindication to rituximab as per national label
- Use of disease-modifying anti-rheumatic drugs (DMARDs; including methotrexate) for less than 3 months or change in dosing regimen within 28 days before SD1, or methotrexate dose regimen >25 mg/week
- Participation in any interventional clinical trial within 1 month before SD1 (or within 5 half-lives of the investigated compound before SD1, whichever is longer)
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 |
|---|---|---|
| RituximabRituximab will be administered as an intravenous infusion at a dose of 1000 mg at Weeks 1 and 3. | Biological | Rituximab Plus Atacicept, Rituximab Plus Placebo |
| AtaciceptAtacicept will be administered at a dose of 150 mg subcutaneously once a week from Week 7 to 32. | Drug | Rituximab Plus Atacicept |
| Placebo matched to ataciceptPlacebo matched to atacicept will be administered subcutaneously once a week from Week 7 to 32. | Drug | Rituximab Plus Placebo |
Primary outcome
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Baseline up to Week 64
An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Percentage of Participants With Immunoglobulin G (IgG) Level Less Than 3 Gram Per Liter (g/L)
Time frame: Week 64
Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32
Time frame: Baseline, Week 32
Vital signs assessed included blood pressure (systolic and diastolic), pulse and body temperature. Routine safety lab parameters evaluated included red blood cell (RBC), hemoglobin, hematocrit, platelets, mean cellular hemoglobin (MCH), MCH concentration, MCH volume, white blood cell (WBC), lymphocytes, monocytes, eosinophils, basophils, neutrophils, gamma glutamyl transferase (GGT), alanine aminotransferase (ALT), albumin, alkaline phosphatase (AP), aspartate aminotransferase (AST), bilirubin, calcium, creatinine, glucose, potassium, total protein, sodium, uric acid, and blood urea nitrogen. Percent change from baseline was calculated as ([Week 32 value minus baseline value] multiplied by 100) divided by baseline value.
Percent Change From Baseline in Anti-tetanus and Anti-diphteria Immunization Titer at Week 32
Time frame: Baseline, Week 32
Percent change from baseline was calculated as ([Week 32 value minus baseline value] multiplied by 100) divided by baseline value.
Percent Change From Baseline in Anti-pneumococcus Titer at Week 32
Time frame: Baseline, Week 32
Percent change from baseline was calculated as ([Week 32 value minus baseline value] multiplied by 100) divided by baseline value.
3 secondary outcomes
Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP), ACR50-CRP and ACR70-CRP at Week 32
Time frame: Week 32
Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) at Week 32
Time frame: Baseline, Week 32
Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells
Time frame: Baseline, Week 3, 7, 12, 16, 26 and 32
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26137975van Vollenhoven RF, Wax S, Li Y, Tak PP. Safety and efficacy of atacicept in combination with rituximab for reducing the signs and symptoms of rheumatoid arthritis: a phase II, randomized, double-blind, placebo-controlled pilot trial. Arthritis Rheumatol. 2015 Nov;67(11):2828-36. doi: 10.1002/art.39262.
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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.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab and Atacicept in people with Rheumatoid Arthritis, run by Merck KGaA, Darmstadt, Germany at 8 sites in 4 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 7 inclusion and 12 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 30 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in France, Sweden, United Kingdom, Netherlands. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 30 Dec 2016). 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?
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Baseline up to Week 64). 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 NCT00664521, 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 30 Dec 2016.