Clinical trial NCT05869955: A Study of CC-97540, CD-19-Targeted Nex-T CAR T Cells, in Participants With Severe, Refractory Autoimmune Diseases (Breakfree-1)
Official title: A Phase 1, Multicenter, Open-Label Study Of CC-97540 (BMS-986353), CD19-Targeted Nex-T Chimeric Antigen Receptor (CAR) T Cells, in Participants With Severe, Refractory Autoimmune Diseases: Systemic Lupus Erythematosus, Idiopathic Inflammatory Myopathy or Systemic Sclerosis (Breakfree-1)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus
Idiopathic Inflammatory Myopathy
Systemic Sclerosis
Keywords: CC-97540
BMS-986353
Lead sponsor: Juno Therapeutics, Inc., a Bristol-Myers Squibb Company
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb Services Unlimited Company
First posted: 2023-05-23
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to establish the tolerability, preliminary efficacy, and pharmacokinetics of CC-97540 in participants with severe, refractory autoimmune diseases (Breakfree-1).


Eligibility criteria: Inclusion Criteria

- Diagnosis of Systemic Lupus Erythematosus (SLE) defined as follows:.

i) Fulfilling the 2019 European League Against Rheumatism (EULAR) / American College of Rheumatology (ACR) classification criteria of SLE.

ii) Presence of anti-dsDNA, anti-histone, anti-chromatin, anti-Ro (anti-SS-A), anti-La (anti-SS-B), or anti-Sm antibodies at screening.

- SLE disease activity.

i) Active disease at screening, with recent ≥ 1 major organ system with a BILAG A score (excluding musculoskeletal, mucocutaneous, and/or constitutional organ system).

ii) Inadequate response to glucocorticoids and to at least 2 of the following treatments, used for at least 3 months each: cyclophosphamide, mycophenolic acid or its derivatives, belimumab, azathioprine, anifrolumab, methotrexate, rituximab, obinutuzumab, cyclosporin, tacrolimus or voclosporin.

- Diagnosis of Idiopathic Inflammatory Myopathy (IIM) defined as follows:.

i) Fulfilling the 2017 EULAR/ACR classification criteria for probable or definite IIM.

ii) Participant diagnosed with the following IIM subgroups: dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), anti-synthetase syndrome (ASyS), and polymyositis (PM).

iii) Presence of at least 1 myositis specific antibody (MSA), associated antibody (MAA), or ANA at screening or prior to screening.

- IIM disease activity.

i) Severe muscle AND/OR skin involvement.

ii) Proof of activity as documented by:.

A. An active myositis-associated rash OR.

B. A recent muscle biopsy OR.

C. An elevated CK \> 3 times the upper limit of normal OR.

D. Participants diagnosed IIM AND progressive Interstitial Lung Disease (ILD) on high-resolution computed tomography (HRCT)

iii) Inadequate response to glucocorticoids and at least 2 of the following treatments used for at least 3 months: azathioprine, methotrexate, cyclosporin A, tacrolimus, MMF, cyclophosphamide, IVIG, JAK inhibitors, and rituximab.

- Diagnosis of Systemic Sclerosis (SSc) defined as follows:.

i) Fulfilling 2013 EULAR/ACR classification criteria for SSc.

ii) Antinuclear Antibody (ANA) positive at screening or prior to screening.

- SSc disease activity.

i) Participants diagnosed with diffuse cutaneous SSc OR diffuse or limited cutaneous SSc AND progressive ILD, AND.

ii) Inadequate response to at least 1 of the following treatments used for at least 3 months: mycophenolate, cyclophosphamide, rituximab, nintedanib, azathioprine, tocilizumab, or intravenous immunoglobulins (IVIG).

Exclusion Criteria

* Diagnosis of drug-induced SLE rather than idiopathic SLE.
* Other systemic autoimmune diseases (eg, multiple sclerosis, psoriasis, inflammatory bowel disease, etc) are excluded. Participants with type I autoimmune diabetes mellitus, thyroid autoimmune disease, Celiac disease, or secondary Sjögren's syndrome are not excluded.
* SLE overlap syndromes including, but not limited to, rheumatoid arthritis, scleroderma, and mixed connective tissue disease, are excluded.
* Present or recent clinically significant CNS pathology, within 12 months.
* IIM disease activity.

  i) Other forms of IIM: Inclusion Body Myositis, Amyopathic DM, any form of juvenile myositis.

ii) Myositis other than IIM, eg, drug-induced myositis and PM associated with HIV.

iii) Participants with severe muscle damage (Physician VAS for muscle damage in Myositis Damage Index \> 7 cm on a 10 cm scale), permanent weakness due to a non-IIM cause (eg, stroke), or myositis with cardiac involvement.

- SSc disease activity.

i) SSc related PAH requiring active treatment.

ii) Rapidly progressive SSc related lower GI (small and large intestines) involvement (requiring parenteral nutrition); active gastric antral vascular ectasia.

iii) Prior scleroderma renal crisis.

- Other protocol-defined Inclusion/Exclusion criteria apply.

Primary outcomes:
measure: Number of participants with treatment-emergent adverse events (AEs) in each indication.
timeFrame: Up to 2 years after CC-97540 infusion
measure: Number of participants with serious AEs (SAEs) in each indication.
timeFrame: Up to 2 years after CC-97540 infusion
measure: Number of participants with AEs of special interest (AESI) in each indication.
timeFrame: Up to 2 years after CC-97540 infusion
measure: Number of participants with laboratory abnormalities in each indication.
timeFrame: Up to 2 years after CC-97540 infusion
measure: Number of participants with Dose Limiting Toxicities (DLT) in each indication.
timeFrame: Up to 2 years after CC-97540 infusion
measure: Recommended Phase 2 Dose (RP2D) of CC-97540 in each indication.
timeFrame: Up to 2 years after CC-97540 infusion
Secondary outcomes:
measure: Proportion of participants achieving definition of remission in SLE (DORIS) remission
timeFrame: At week 24
measure: Proportion of participants achieving Lupus Low Disease Activity State (LLDAS)
timeFrame: At week 24
measure: Change in proteinuria measured by urine protein creatinine ratio (UPCR)
timeFrame: At week 24
measure: Change in Health Assessment Questionnaire - Disability Index (HAQ-DI)
timeFrame: At week 24
measure: Proportion of participants achieving Myositis Response Criteria (MRC) Total Improvement Score (TIS) Major Response
timeFrame: At Week 24
measure: Change in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)
timeFrame: At Week 24
measure: Proportion of participants with ILD with no worsening of pulmonary function including forced expiratory volume (FEV1) (> 10%), forced vital capacity (FVC) (> 10%), and diffusing capacity of the lung for carbon monoxide (DLCO) (> 15%)
timeFrame: At Week 24
measure: Proportion of participants achieving a minimal clinically important difference (MCID) of 24% change from baseline of the modified Rodnan Skin Score (mRSS)
timeFrame: At Week 24
measure: Participants with an improvement from baseline of the Revised Composite Response Index in Systemic Sclerosis (CRISS)
timeFrame: At Week 24
measure: The worsening of pulmonary function including FVC (>10% absolute), DLCO (>15% absolute decline) in participants with interstitial lung disease (ILD)
timeFrame: At Week 24
measure: Maximum observed blood concentration (Cmax)
timeFrame: Up to 2 years
measure: Time of maximum observed blood concentration (Tmax)
timeFrame: Up to 2 years
measure: Area under the blood concentration-time curve from time zero to 28 days after dosing (AUC(0-28D))
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: New Haven
country: United States
facility: Local Institution - 0048
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital and Clinics, Sylvester Cancer Center
state: Florida
city: Chicago
country: United States
facility: Local Institution - 0053
state: Illinois
city: Baltimore
country: United States
facility: Local Institution - 0030
state: Maryland
city: Boston
country: United States
facility: Local Institution - 0038
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0046
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Chan Medical School
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Chan Medical School
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Medical Center - New Center One
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic in Rochester, Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University Of Nebraska Medical Center
state: Nebraska
city: Summit
country: United States
facility: Atlantic Health System Overlook Medical Center
state: New Jersey
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Local Institution - 0054
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: New York
country: United States
facility: Local Institution - 0055
state: New York
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Local Institution - 0027
state: Ohio
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Seattle
country: United States
facility: Local Institution - 0057
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaams-Brabant
city: Strasbourg
country: France
facility: Local Institution - 0043
state: Alsace
city: Pessac
country: France
facility: CHU Bordeaux Haut-Leveque
state: Aquitaine
city: Montpellier
country: France
facility: CHU Montpellier Lapeyronie Hospital
state: Hérault
city: Lille
country: France
facility: Hopital Claude Huriez - CHU de Lille
city: Nice
country: France
facility: Centre Hospitalier Universitaire de Nice - Hôpital l'Archet
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Local Institution - 0052
city: Rennes
country: France
facility: Centre Hospitalier Universitaire de Rennes - Hôpital Pontchaillou
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
state: Bayern
city: Köln
country: Germany
facility: Universitaetsklinikum Koeln
state: Nordrhein-Westfalen
city: Magdeburg
country: Germany
facility: Local Institution - 0045
state: Sachsen-Anhalt
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
state: Sachsen
city: Berlin
country: Germany
facility: Charité Universitaetsmedizin Berlin - Campus Mitte
city: Düsseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore
state: Lazio
city: Rozzano
country: Italy
facility: Humanitas
state: Milano
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [Barcelona]
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
state: Cantabria
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
state: Catalunya [Cataluña]
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Málaga
country: Spain
facility: H.R.U Málaga - Hospital General
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: