Clinical trial NCT06570798: A Phase 2a Master Protocol Assessing Inebilizumab and Blinatumomab in Autoimmune Diseases
Official title: A Phase 2a, Open Label, Multicenter, Platform Trial to Assess the Safety, Tolerability, and Efficacy of Inebilizumab and Blinatumomab in Subjects With Autoimmune Diseases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Active Refractory Rheumatoid Arthritis
Keywords: Systemic lupus erythematosus
Inebilizumab
Blinatumomab
Active refractory rheumatoid arthritis
Rheumatoid arthritis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2024-08-26
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Subprotocol A: Sequential study model Subprotocol B: Sequential study model Subprotocol C: Sequential study model
Primary purpose: TREATMENT

Brief summary: The main objective is to assess the safety and tolerability of inebilizumab in adult participants with active and refractory systemic lupus erythematosus (SLE) with nephritis (Subprotocol A) and to assess the safety and tolerability of subcutaneous (SC) blinatumomab in adult participants with active and refractory SLE with nephritis (Subprotocol B) and in adult participants with active refractory rheumatoid arthritis (RA) (Subprotocol C).


Eligibility criteria: Inclusion Criteria:

* Subprotocol A and B: Diagnosis of SLE according to 2019 European League Against Rheumatism and the American College of Rheumatology (ACR) classification criteria.
* Subprotocol A and B: Participant must be positive for at least one of the following autoantibodies at screening (performed by central laboratory) or through documented history:

  1. Antinuclear antibodies (ANA) ≥ 1:80
  2. Anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibodies elevated to above normal range (ie, positive results)
  3. Anti-Smith antibodies elevated to above normal (ie, positive results).
* Subprotocol A and B: Active, biopsy-proven, proliferative LN demonstrating class III or class IV with or without co-existing features of Class V LN according to 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria. The local biopsy report will be used.
* Subprotocol A and B: Inadequate response, loss of response or intolerance to at least 1 therapy (Subprotocol A) or 2 therapies (Subprotocol B) at the maximally tolerated doses as recommended by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines (KDIGO, 2024). Inadequate response is defined as: UPCR ≥ 1.0 mg/mg
* Subprotocol A and B: If receiving any of the following medications, participants must be on these doses prior to day 1:

  1. Prednisone dose ≤ 20 mg/day (or its equivalent in other corticosteroid forms) and at a stable dose for 5 days
  2. Hydroxychloroquine dose ≤ 400 mg/day and at a stable dose for 4 weeks. Other equivalent antimalarials (chloroquine, quinacrine) are also accepted at a stable dose for 4 weeks.
  3. MMF dose ≤ 3 g/day or MPA dose ≤ 2160 mg/day and at a stable dose for 2 weeks.
  4. AZA dose ≤ 2 mg/kg/day and at a stable dose for 2 weeks.
* Subprotocol C: Diagnosis of RA according to the 2010 ACR/ European Alliance of Associations for Rheumatology (EULAR) classification criteria.
* Subprotocol C: Active disease defined as having all the following criteria:

  1. DAS28-CRP \> 3.2 at screening
  2. at least 6 tender joints at screening
  3. at least 6 swollen joints at screening
* Subprotocol C: Refractory disease defined as:
* Moderate to severe active disease despite having received treatment with:

  1. at least 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD), AND
  2. at least 2 biologic disease-modifying antirheumatic drugs (bDMARDs) of different mechanisms of action OR 1 bDMARD and at least 1 targeted synthetic disease-modifying antirheumatic drugs (tsDMARD).
* Inadequate response or intolerance to csDMARDs, bDMARDs, and tsDMARDs should be defined as:

  1. Participant having active disease despite a minimum of 12 weeks of treatment with a csDMARD, bDMARD, or tsDMARD.
  2. Intolerance to treatment as defined by participant having experienced an adverse effect from treatment with a csDMARD, bDMARD, or tsDMARD.

Exclusion Criteria:

* Subprotocol A and B: Estimated glomerular filtration rate (eGFR) of \< 30 mL per minute per 1.73 m\^2 of body surface area (calculated using the Modification of Diet in Renal Disease \[MDRD\] formula, with screening laboratory results for serum creatinine value).
* Subprotocol A and B: Significant likely irreversible organ damage related to SLE (eg, end-stage renal disease \[ESRD\]).
* Subprotocol A and B: Any acute, severe lupus related flare during screening that needs immediate treatment.
* Subprotocol A and B: A previous kidney transplant or planned transplant within study treatment period.
* Subprotocol A and B: History of or current renal diseases (other than LN) that in the opinion of the investigator could interfere with the LN assessment and confound the disease activity assessment (eg, diabetic nephropathy).
* Subprotocol A and B: Renal biopsy showing pure class V.
* Subprotocol C: Prior history of current inflammatory joint disease other than RA including but not limited to systemic lupus erythematosus, mixed connective tissue disorder, scleroderma, polymyositis, or significant systemic involvement secondary to RA (eg, vasculitis, pulmonary fibrosis, or Felty's syndrome).
* Subprotocol C: Functional Class IV as defined by the ACR classification of functional status in RA.

Primary outcomes:
measure: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)
timeFrame: Day 1 to Week 52
measure: Number of Participants Who Experience a Serious TEAE
timeFrame: Day 1 to Week 52
Secondary outcomes:
measure: Subprotocol A and B: Number of Participants With a 24-hour Urine Protein-creatinine Ratio (UPCR) ≤ 0.5 mg/mg
timeFrame: Week 12, Week 26, Week 38, and Week 52
measure: Subprotocol A and B: Number of Participants With Remission in SLE as Defined by Definition of Remission in SLE (DORIS)
timeFrame: Week 12, Week 26, Week 38, and Week 52
measure: Subprotocol A and B: Number of Participants With a Lupus Low Disease Activity State (LLDAS)
timeFrame: Week 12, Week 26, Week 38, and Week 52
measure: Subprotocol A and B: Change From Baseline in SLE Activity Index-2000 (SLEDAI-2K) Score
timeFrame: Week 12, Week 26, Week 38, and Week 52
measure: Subprotocol A and B: Percent Change From Baseline in SLEDAI-2K Score
timeFrame: Week 12, Week 26, Week 38, and Week 52
measure: Subprotocol A and B: Change From Baseline in 24-hour UPCR
timeFrame: Week 12, Week 26, Week 38, and Week 52
measure: Subprotocol A and B: Percent Change From Baseline in 24-hour UPCR
timeFrame: Week 12, Week 26, Week 38, and Week 52
measure: Subprotocol A: Maximum Concentration (Cmax) of Inebilizumab
timeFrame: Day 1 to Week 52
measure: Subprotocol A: Time to Cmax (tmax) of Inebilizumab
timeFrame: Day 1 to Week 52
measure: Subprotocol A: Area Under the Concentration-time Curve (AUC) of Inebilizumab
timeFrame: Day 1 to Week 52
measure: Subprotocol B and C: Cmax of Blinatumomab
timeFrame: Day 1 to Week 12
measure: Subprotocol B and C: tmax of Blinatumomab
timeFrame: Day 1 to Week 12
measure: Subprotocol B and C: AUC of Blinatumomab
timeFrame: Day 1 to Week 12
measure: Subprotocol A: Number of Participants With Anti-inebilizumab Antibody Formation
timeFrame: Day 1 to Week 52
measure: Subprotocol B and C: Number of Participants With Anti-blinatumomab Antibody Formation
timeFrame: Day 1 to Week 52
measure: Subprotocol C: Percentage of participants achieving Disease Activity Score-28 Joint C-Reactive Protein (DAS28-CRP) < 2.6
timeFrame: Week 12 and Week 26
measure: Subprotocol C: Percentage of participants achieving Clinical Disease Activity Index (CDAI) ≤ 2.8
timeFrame: Week 12 and Week 26
measure: Subprotocol C: Percentage of participants achieving Simplified Disease Activity Index (SDAI) ≤ 3.3
timeFrame: Week 12 and Week 26
measure: Subprotocol C: Percentage of participants achieving American College of Rheumatology (ACR)20 response
timeFrame: Week 12 and Week 26
measure: Subprotocol C: Percentage of participants achieving ACR50 response
timeFrame: Week 12 and Week 26
measure: Subprotocol C: Percentage of participants achieving ACR70 response
timeFrame: Week 12 and Week 26
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research and Innovation Institute
state: Arizona
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Hialeah
country: United States
facility: Vida Research Center
state: Florida
city: Homestead
country: United States
facility: Homestead Associates In Research Inc
state: Florida
city: Miami
country: United States
facility: Vitaly Clinical Research
state: Florida
city: Great Neck
country: United States
facility: Northwell Health
state: New York
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Houston
country: United States
facility: Prolato Clinical Research Center
state: Texas
city: Bruxelles
country: Belgium
facility: Cliniques Universtaire Saint Luc Universite Catholique de Louvain
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire de Liege - Sart Tilman
city: Lille cedex 01
country: France
facility: Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez
city: Lyon Cédex 3
country: France
facility: Centre Hospitalier Universitaire de Lyon - Hopital Edouard Herriot
city: Marseille
country: France
facility: Hopital de la Conception
city: Paris cedex 15
country: France
facility: Hopital Europeen Georges Pompidou
city: Paris
country: France
facility: Hopital Bichat Claude Bernard
city: Strasbourg
country: France
facility: Centre Hospitalier Universitaire de Strasbourg - Nouvel Hopital Civil
city: Toulouse Cedex 9
country: France
facility: Centre Hospitalier Universitaire de Toulouse - Hopital Rangueil
city: Muenchen
country: Germany
facility: Klinikum der LMU Muenchen
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Rozzano
country: Italy
facility: IRCCS Istituto Clinico Humanitas
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
state: Cataluña
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: