Systemic Lupus ErythematosusPhase 3BEGINNCT00539838
A Study to Evaluate Two Doses of Ocrelizumab in Patients With Active Systemic Lupus Erythematosus (BEGIN)
A Phase 3 study testing Prednisone, Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate) and Methylprednisolone in people with Systemic Lupus Erythematosus, run by Genentech, Inc..
Trial summary
This is a Phase III, randomized, double blind, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of ocrelizumab compared to placebo when combined with a single stable background immunosuppressive medication and a corticosteroid regimen in patients with moderately to severely… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Systemic Lupus Erythematosus
- What is being tested?
- Prednisone, Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate) and Methylprednisolone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- No sites listed yet
- Study dates
- 19 Dec 2007to 12 Jul 2011
- Phase
- Phase 3
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 16 years or above at the time of screening
- Diagnosis of SLE
- Active disease at screening
Who cannot join
- Presence of active moderate to severe glomerulonephritis
- Currently active retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia
- Lack of peripheral venous access
- Pregnancy or breast feeding mothers
- History of severe allergic or anaphylactic reactions to humanized, chimeric or murine monoclonal antibodies or i.v. immunoglobulin
- Known severe chronic pulmonary disease
Show all 24Show fewer
- Evidence of significant or uncontrolled concomitant diseases in any organ system not related to SLE, which, in the investigator's opinion, would impair patient participation
- Concomitant condition which has required treatment with systemic corticosteroid (excluding topical or inhaled) at any time in the 52 weeks prior to screening
- Known HIV or chronic active Hepatitis B or chronic active Hepatitis C infection
- Known active infection of any kind (but excluding fungal infection of nail beds or oral thrush which has resolved before Day 1) within 30 days prior to Day 1. In addition, any major episode of infection requiring hospitalization or treatment with intravenous anti-infectives in the 30 days prior to Day 1 or oral anti-infectives in the 14 days prior to Day 1
- History of serious recurrent or chronic infection
- History of cancer (except basal cell carcinoma of the skin that has been excised and cured)
- History of alcohol or drug abuse in the 52 weeks prior to screening
- Major surgery in the 4 weeks prior to screening excluding diagnostic surgery
- Previous treatment with CAMPATH-1H
- Previous treatment with a BAFF directed treatment in the 12 months prior to screening
- Previous treatment with a B-cell targeted therapy other than one directed at BAFF
- Treatment with any investigational agent, other than those above, in the 28 days prior to screening or five half-lives of the investigational drug (whichever is longer)
- Receipt of any live vaccine in the 6 weeks prior to Day 1
- Intolerance or contraindication to oral or i.v. corticosteroids
- Treatment with a second immunosuppressive or immunomodulatory drug in the 8 weeks prior to Day 1
- Prednisone dose of ≥ 0.7 mg/kg/day (or equivalent) for > 7 of the previous 30 days prior to screening
- Treatment with cyclophosphamide or a calcineurin inhibitor in the 12 weeks prior to screening
- Positive hepatitis BsAg or hepatitis C serology. Patients who are HBsAg negative but HBcAb positive may be enrolled with a negative DNA test
About this study
Official title: A Randomised, Double-Blind, Placebo Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy and Safety of Two Doses of Ocrelizumab in Patients With Active Systemic Lupus Erythematosus
This is a Phase III, randomized, double blind, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of ocrelizumab compared to placebo when combined with a single stable background immunosuppressive medication and a corticosteroid regimen in patients with moderately to severely active systemic lupus erythematosus, who do not have moderate to severe glomerulonephritis.
- Conditions
- Systemic Lupus Erythematosus
- Being tested
- Prednisone, Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate), Methylprednisolone, Ocrelizumab, Placebo
- Keywords
- SLE
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrednisoneDrug
Oral repeating dose
Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate)Drug
Oral repeating dose
Intravenous repeating dose
OcrelizumabDrug
Intravenous repeating dose
PlaceboDrug
Intravenous repeating dose
| Study group | Role | What they receive |
|---|---|---|
| Ocrelizumab 1000 mg | Experimental | Ocrelizumab was administered i.v. at a dose on Days 1 and 15, followed by 1000 mg i.v. at Week 16 and then every 16 weeks Receives: Drug: Prednisone; Drug: Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate); Drug: Methylprednisolone; Drug: Ocrelizumab |
| Ocrelizumab 400 mg | Experimental | Ocrelizumab was administered at a dose 400 mg i.v. on Days 1 and 15, followed by 400 mg i.v. at Week 16 and then every 16 weeks Receives: Drug: Prednisone; Drug: Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate); Drug: Methylprednisolone; Drug: Ocrelizumab |
| Placebo | Placebo comparator | Placebo infusions were administered on Days 1 and 15, followed by placebo infusion at Week 16 and then every 16 weeks Receives: Drug: Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate); Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Major Clinical Response (MCR)
Measured: Week 48
Number of Participants With Partial Clinical Response (PCR)
Measured: Week 48
Number of Non-responders (NR)
Measured: Week 48
Secondary outcomes (12)
Number of Participants Who Achieved a BILAG Score of C or Better at Week 24.
Measured: Week 24
Time Adjusted Mean SLEDAI-2K Score
Measured: Week 48
Annualized Flare Rate
Measured: Week 48 to Week 96
Time to First Moderate to Severe Flare
Measured: Week 48 to Week 96
Number of Participants Who Achieved A Major Or Partial Clinical Response At Week 48 (PCR Plus MCR Proportion), Who Did Not Experience A Flare Before Week 96
Measured: Week 48 to Week 96
Number of Participants Who Achieved A MCR At Week 48, Who Did Not Experience A Flare Before Week 72
Measured: Week 48 to Week 72
Number of Participants Achieved A MCR At Week 48, Who Did Not Experience A Flare Before Week 96
Measured: Week 48 to Week 96
Change in SF-36 Subscale And Summary Scores From Baseline At Week 48
Measured: Baseline, Week 48
Change In FACIT-Fatigue Assessment From Baseline To Week 48
Measured: Baseline, Week 48
Change From Baseline In Pain Quality And Impact Of Pain On Daily Function Measured By The Brief Pain Inventory Short Form At Week 48
Measured: Baseline, Week 48
The EQ-5D Single Index Utility Score At Week 48
Measured: Baseline, Week 48
Number of Participants With Adverse Events
Measured: Up to 2.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2007 (estimated)
- Study start19 Dec 2007
- Primary completion12 Jul 2011
- Study completion12 Jul 2011
Why it stopped: The study was terminated prematurely when the decision was made that ocrelizumab was not likely to benefit this patient population.
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.
- Other trials for Systemic Lupus ErythematosusStudies of the same condition, open and under way.
- More trials run by Genentech, 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Roche Pharma AG
- Responsible party
- Sponsor
- Investigators
- Jorn Drappa, M.D., Ph.D., Study director, Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00539838
- Sponsor's protocol ID
- ACT4071g
- Other IDs
- WA20499
- Acronym
- BEGIN
- Status last verified
- Aug 2020
- First submitted
- 3 Oct 2007
- Last updated
- 17 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- Yes: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-Blind, Placebo Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy and Safety of Two Doses of Ocrelizumab in Patients With Active Systemic Lupus Erythematosus
- ClinicalTrials.gov ID
- NCT00539838
- Acronym / sponsor ID
- BEGIN / ACT4071g
- Conditions
- Systemic Lupus Erythematosus
- Keywords
- SLE
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated prematurely when the decision was made that ocrelizumab was not likely to benefit this patient population.
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Roche Pharma AG
- Study start
- 19 Dec 2007 (actual)
- Primary completion
- 12 Jul 2011 (actual)
- Study completion
- 12 Jul 2011 (actual)
- First posted
- 5 Oct 2007 (estimated)
- Results
- Posted 17 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase III, randomized, double blind, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of ocrelizumab compared to placebo when combined with a single stable background immunosuppressive medication and a corticosteroid regimen in patients with moderately to severely active systemic lupus erythematosus, who do not have moderate to severe glomerulonephritis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Ocrelizumab 1000 mg | Experimental | Drug: Prednisone, Drug: Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate), Drug: Methylprednisolone, Drug: OcrelizumabOcrelizumab was administered i.v. at a dose on Days 1 and 15, followed by 1000 mg i.v. at Week 16 and then every 16 weeks |
| Ocrelizumab 400 mg | Experimental | Drug: Prednisone, Drug: Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate), Drug: Methylprednisolone, Drug: OcrelizumabOcrelizumab was administered at a dose 400 mg i.v. on Days 1 and 15, followed by 400 mg i.v. at Week 16 and then every 16 weeks |
| Placebo | Placebo comparator | Drug: Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate), Drug: PlaceboPlacebo infusions were administered on Days 1 and 15, followed by placebo infusion at Week 16 and then every 16 weeks |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Age 16 years or above at the time of screening
- Diagnosis of SLE
- Active disease at screening
Key exclusion criteria (24 listed)
- Presence of active moderate to severe glomerulonephritis
- Currently active retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia
- Lack of peripheral venous access
- Pregnancy or breast feeding mothers
- History of severe allergic or anaphylactic reactions to humanized, chimeric or murine monoclonal antibodies or i.v. immunoglobulin
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 |
|---|---|---|
| PrednisoneOral repeating dose | Drug | Ocrelizumab 1000 mg, Ocrelizumab 400 mg |
| Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate)Oral repeating dose | Drug | Ocrelizumab 1000 mg, Ocrelizumab 400 mg, Placebo |
| MethylprednisoloneIntravenous repeating dose | Drug | Ocrelizumab 1000 mg, Ocrelizumab 400 mg |
| OcrelizumabIntravenous repeating dose | Drug | Ocrelizumab 1000 mg, Ocrelizumab 400 mg |
| PlaceboIntravenous repeating dose | Drug | Placebo |
Primary outcome
Number of Participants With Major Clinical Response (MCR)
Time frame: Week 48
Number of Participants With Partial Clinical Response (PCR)
Time frame: Week 48
Number of Non-responders (NR)
Time frame: Week 48
12 secondary outcomes
Number of Participants Who Achieved a BILAG Score of C or Better at Week 24.
Time frame: Week 24
Time Adjusted Mean SLEDAI-2K Score
Time frame: Week 48
Annualized Flare Rate
Time frame: Week 48 to Week 96
Time to First Moderate to Severe Flare
Time frame: Week 48 to Week 96
Number of Participants Who Achieved A Major Or Partial Clinical Response At Week 48 (PCR Plus MCR Proportion), Who Did Not Experience A Flare Before Week 96
Time frame: Week 48 to Week 96
Number of Participants Who Achieved A MCR At Week 48, Who Did Not Experience A Flare Before Week 72
Time frame: Week 48 to Week 72
Number of Participants Achieved A MCR At Week 48, Who Did Not Experience A Flare Before Week 96
Time frame: Week 48 to Week 96
Change in SF-36 Subscale And Summary Scores From Baseline At Week 48
Time frame: Baseline, Week 48
Change In FACIT-Fatigue Assessment From Baseline To Week 48
Time frame: Baseline, Week 48
Change From Baseline In Pain Quality And Impact Of Pain On Daily Function Measured By The Brief Pain Inventory Short Form At Week 48
Time frame: Baseline, Week 48
The EQ-5D Single Index Utility Score At Week 48
Time frame: Baseline, Week 48
Number of Participants With Adverse Events
Time frame: Up to 2.5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
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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.
Jorn Drappa, M.D., Ph.D. study director
Genentech, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Prednisone, Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate) and Methylprednisolone in people with Systemic Lupus Erythematosus, run by Genentech, Inc..
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 24 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: stopped early, as of the sponsor's last update on 17 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 17 Sep 2020). 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 Major Clinical Response (MCR) (time frame: Week 48). The study lists 3 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 17 Sep 2020.