A Study to Evaluate the Efficacy and Safety of Obinutuzumab in Participants With Systemic Lupus Erythematosus (ALLEGORY)

• ClinicalTrials.gov Identifier: NCT04963296
• Recruitment Status: Recruiting
• First Posted: July 15, 2021
• Last Update Posted: April 18, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: July 7, 2021
• First Posted Date: July 15, 2021
• Last Update Posted Date: April 18, 2024
• Actual Study Start Date: October 26, 2021
• Estimated Primary Completion Date: November 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 7, 2021)

Percentage of Participants who Achieve Systemic Lupus Erythematosus Responder Index (SRI[4]) at Week 52 [ Time Frame: Week 52 ]

SRI(4) requires reduction from baseline of >=4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), no new systems or organs affected, as defined by >=1 new British Isles Lupus Assessment Group (BILAG) A or >=2 new BILAG B items compared with baseline using BILAG-2004, and no worsening from baseline of >=0.30 points on a 3-point Physician's Global Assessment Visual Analogue Scale (PGA-VAS).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 17, 2023)

• Percentage of Participants who Achieve SRI(6) at Week 52 [ Time Frame: Week 52 ]
  SRI(6) requires reduction from baseline of >=6 points in the SLEDAI-2K, no new systems or organs affected, as defined by >=1 new BILAG A or >=2 new BILAG B items compared with baseline using BILAG-2004, and no worsening from baseline of >=0.30 points on a 3-point PGA-VAS.
• Percentage of Participants Entering the Study on Prednisone >= 10 mg/day (or equivalent) who Achieve Sustained Corticosteroid Control [ Time Frame: From Week 40 to Week 52 ]
  No treatment with prednisone >=7.5 mg/day (or equivalent) and no receipt of intravenous, intramuscular, or intra-articular corticosteroids.
• Time to First BILAG Flare over 52 Weeks [ Time Frame: From baseline to Week 52 ]
  Flare is defined as the occurrence of >=1 new BILAG A or >=2 new BILAG B manifestations from the previous visit
• Percentage of Participants who Achieve a Sustained SRI(4) Response [ Time Frame: From Week 40 to Week 52 ]
  Achievement of SRI(4) at all study visits from Week 40 through Week 52.
• Percentage of Participants who Achieve British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) at Week 52 [ Time Frame: Week 52 ]
  Reduction of all baseline BILAG-2004 A items to B/C/D and baseline BILAG-2004 B items to C/D; no new systems or organs affected, as defined by >=1 new BILAG A or >=2 new BILAG B items compared with baseline; no net increase in SLEDAI-2K score from baseline; and no worsening from baseline of >=0.30 points on a 3-point PGA-VAS.
• Percentage of Participants who Achieve SRI(8) at Week 52 [ Time Frame: Week 52 ]
• Percentage of Participants who Achieve SRI(4) at Week 24 [ Time Frame: Week 24 ]
• Percentage of Participants who Achieve Clinical SRI(4) at Week 52 [ Time Frame: Week 52 ]
• Percentage of Participants who Achieve SRI(4) at Week 52 on Low-dose Corticosteroids [ Time Frame: Week 52 ]
• Percentage of Participants who Achieve Lupus Low Disease Activity State (LLDAS) at Week 52 [ Time Frame: Week 52 ]
• Percentage of Participants who Achieve Definition of Remission in SLE (DORIS) at Week 52 [ Time Frame: Week 52 ]
• Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale [ Time Frame: From baseline to Week 24 and from baseline to Week 52 ]
• Change in 36-Item Short Form Survey, Version 2 (SF-36 v2) Bodily Pain Domain Scale [ Time Frame: From baseline to Week 24 and from baseline to Week 52 ]
• Change in SF-36 v2 Physical Component Summary Scale [ Time Frame: From baseline to Week 24 and from baseline to Week 52 ]
• Change in Active Joint Count (Swollen plus Tender) [ Time Frame: From baseline to Week 24 and from baseline to Week 52 ]
• Percentage of Participants who Achieve a >= 50% Reduction in Active Joint Counts (Swollen plus Tender) at Each Study Visit [ Time Frame: From baseline to Week 52 ]
• Percentage of Participants who Achieve a >= 50% Reduction in Cutaneous Lupus Erythematosus Disease Area and Severity (CLASI) Total Activity Score at each Study Visit, among Participants with CLASI Total Activity Score >=10 at Baseline [ Time Frame: From baseline to Week 52 ]
• Percentage of Participants who Achieve Sustained Corticosteroid Control [ Time Frame: From Week 40 through Week 52 ]
• Cumulative Corticosteroid use (in Equivalent Milligrams of Prednisone) [ Time Frame: From baseline to Week 52 ]
• Annualized flare rate through Week 52 [ Time Frame: At Week 52 ]
• Percentage of Participants with Adverse Events [ Time Frame: From baseline to approximately 6 years ]
• Percentage of Participants with Adverse Events of Special Interest (AESIs) [ Time Frame: From baseline to approximately 6 years ]
• Serum Concentration of Obinutuzumab [ Time Frame: Double blind period: At Weeks 2, 4, 12, 24, 26, 36, 52 and at early study discontinuation visit; Open label period: At Weeks 54, 56, 58, 66, 78, 90, 104 and at early study discontinuation visit ]
• Percentage of Participants with Anti-drug Antibodies (ADAs) at Baseline [ Time Frame: Baseline ]
• Percentage of Participants with ADAs During the Study [ Time Frame: Up to approximately 6 years ]

Original Secondary Outcome Measures (submitted: July 7, 2021)

• Percentage of Participants who Achieve SRI(6) at Week 52 [ Time Frame: Week 52 ]
  SRI(6) requires reduction from baseline of >=6 points in the SLEDAI-2K, no new systems or organs affected, as defined by >=1 new BILAG A or >=2 new BILAG B items compared with baseline using BILAG-2004, and no worsening from baseline of >=0.30 points on a 3-point PGA-VAS.
• Percentage of Participants who Achieve Sustained Corticosteroid Control [ Time Frame: From Week 40 to Week 52 ]
  No treatment with prednisone >=5 mg/day (or equivalent) and no receipt of intravenous, intramuscular, or intra-articular corticosteroids.
• Percentage of Participants who Achieve Sustained SRI(4) Response [ Time Frame: From Week 40 to Week 52 ]
  Achievement of SRI(4) at all study visits from Week 40 through Week 52.
• Percentge of Participants who Achieve British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) at Week 52 [ Time Frame: Week 52 ]
  Reduction of all baseline BILAG-2004 A items to B/C/D and baseline BILAG-2004 B items to C/D; no new systems or organs affected, as defined by >=1 new BILAG A or >=2 new BILAG B items compared with baseline; no net increase in SLEDAI-2K score from baseline; and no worsening from baseline of >=0.30 points on a 3-point PGA-VAS.
• Percentage of Participants who Achieve SRI(8) at Week 52 [ Time Frame: Week 52 ]
• Percentge of Participants who Achieve SRI(4) at Week 24 [ Time Frame: Week 24 ]
• Percentage of Participants who Achieve Clinical SRI(4) at Week 52 [ Time Frame: Week 52 ]
• Percentage of Participants who Achieve SRI(4) at Week 52 on Low-dose Corticosteroids [ Time Frame: Week 52 ]
• Percentage of Participants who Achieve Lupus Low Disease Activity State (LLDAS) at Week 52 [ Time Frame: Week 52 ]
• Time to First BILAG Flare [ Time Frame: From baseline to Week 52 ]
• Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale [ Time Frame: From baseline to Week 52 ]
• Change in 36-Item Short Form Survey, Version 2 (SF-36 v2) Bodily Pain Domain Scale [ Time Frame: From baseline to Week 52 ]
• Change in SF-36 v2 Physical Component Summary Scale [ Time Frame: From baseline to Week 52 ]
• Percentage of Participants with Adverse Events [ Time Frame: From baseline to approximately 6 years ]
• Percentage of Participants with Adverse Events of Special Interest (AESIs) [ Time Frame: From baseline to approximately 6 years ]
• Serum Concentration of Obinutuzumab [ Time Frame: Double blind period: At Weeks 2, 4, 12, 24, 26, 36, 52 and at early study discontinuation visit; Open label period: At Weeks 54, 56, 58, 66, 78, 80, 90, 104 and at early study discontinuation visit ]
• Percentage of Participants with Anti-drug Antibodies (ADAs) at Baseline [ Time Frame: Baseline ]
• Percentage of Participants with ADAs During the Study [ Time Frame: Up to approximately 6 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Efficacy and Safety of Obinutuzumab in Participants With Systemic Lupus Erythematosus
• Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Evaluate The Efficacy And Safety of Obinutuzumab in Patients With Systemic Lupus Erythematosus
• Brief Summary: This parallel-group, double-blind, placebo-controlled study will evaluate the efficacy and safety of obinutuzumab versus placebo in participants with active, autoantibody-positive systemic lupus erythematosus (SLE) who are treated with standard-of-care therapy.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Systemic Lupus Erythematosus

Intervention

• Drug: Obinutuzumab
  Obinutuzumab will be administered by IV infusion at a dose of 1000 mg on Day 1 and at Weeks 2, 24 and 26.
  Other Name: Gazyva, GA101, RO5072759
• Drug: Placebo
  Placebo matching obinutuzumab will be administered by IV on Day 1 and at Weeks 2, 24 and 26.
• Drug: Acetaminophen/Paracetamol
  Acetaminophen 650-1000 mg will be administered as premedication prior to infusions.
• Drug: Diphenhydramine hydrochloride
  Diphenhydramine 50 mg will be administered as premedication prior to infusions.
• Drug: Methylprednisolone
  Methylprednisolone 80 mg IV will be administered as premedication prior to infusions.

Study Arms

• Experimental: Obinutuzumab
  Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1 and at Weeks 2, 24 and 26.
  Interventions:

  • Drug: Obinutuzumab
  • Drug: Acetaminophen/Paracetamol
  • Drug: Diphenhydramine hydrochloride
  • Drug: Methylprednisolone
• Placebo Comparator: Placebo
  Placebo participants will receive obinutuzumab matched placebo on Day 1 and at Weeks 2, 24 and 26.
  Interventions:

  • Drug: Placebo
  • Drug: Acetaminophen/Paracetamol
  • Drug: Diphenhydramine hydrochloride
  • Drug: Methylprednisolone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 14, 2023): 300
• Original Estimated Enrollment (submitted: July 7, 2021): 200
• Estimated Study Completion Date: November 30, 2027
• Estimated Primary Completion Date: November 30, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria >=12 weeks prior to screening
• Anti-nuclear antibody (ANA) >=1:80, or anti-dsDNA and/or anti-Sm antibodies above the upper limit of normal (ULN), as determined by the central laboratory at screening
• Low C3 or low C4 or low CH50 complement as determined by the central laboratory at screening
• High disease activity at screening, based on; BILAG-2004 (Category A disease in >=1 organ system and/or Category B disease in >=2 organ systems), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (score >=8) and Physician's Global Assessment (PGA) (score >=1.0 on a 0 to 3 visual analogue scale [VAS])
• High disease activity on Day 1, based on; SLEDAI-2K (score >=8) and PGA (score >=1.0 on a 0 to 3 VAS)
• Current receipt of >=1 of the following classes of standard therapies for the treatment of SLE at stable doses: oral corticosteroid (OCS), antimalarials, conventional immunosuppressants
• Other inclusion criteria may apply
• The Medical Monitor may be consulted if there are any questions related to eligibility criteria

Exclusion Criteria:

• Pregnancy or breastfeeding
• Presence of significant lupus-associated renal disease and/or renal impairment
• Receipt of an excluded therapy, including any anti-CD20, anti-CD19 therapy less than 9 months prior to screening or during screening; or cyclophosphamide, tacrolimus, ciclosporin, or voclosporin during the 2 months prior to screening or during screening
• Significant or uncontrolled medical disease which, in the investigator's opinion, would preclude patient participation
• Known active infection of any kind or recent major episode of infection
• Intolerance or contraindication to study therapies
• Other exclusion criteria may apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: CA42750 https://forpatients.roche.com/; 888-662-6728 (U.S. and Canada); global-roche-genentech-trials@gene.com

• Listed Location Countries: Argentina, Brazil, Czechia, France, Italy, Mexico, New Zealand, Peru, Poland, Russian Federation, South Africa, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04963296
• Other Study ID Numbers: CA42750; 2020-005760-57 ( EudraCT Number ); 2023-504774-38-00 ( Other Identifier: EU CT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: 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/ourmember/roche/). 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).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: April 2024