A Study of CC-97540, CD-19-Targeted Nex-T CAR T Cells, in Participants With Severe, Refractory Autoimmune Diseases

Systemic Lupus Erythematosus Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05869955
• Other study ID #: CA061-1001
• Secondary ID: 2023-503823-24
• Status: Recruiting
• Phase: Phase 1
• Start date: September 13, 2023
• Est. completion date: November 15, 2027

Study information

• Verified date: June 2024
• Source: Juno Therapeutics, Inc., a Bristol-Myers Squibb Company
• Contact: BMS Clinical Trials Contact Center www.BMSClinicalTrials.com
• Phone: 855-907-3286
• Email: Clinical.Trials[@]bms.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 129
• Est. completion date: November 15, 2027
• Est. primary completion date: November 15, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

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

i) Fulfilling the 2019 ACR/EULAR classification criteria of SLE.

ii) Presence of anti-dsDNA, anti-histone, anti-chromatin, or anti-Sm antibodies.

• SLE disease activity.

i) Active disease at screening, defined as = 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.

A. Insufficient response is defined as lack of response, insufficient response or lack of sustained response to appropriate doses. Intolerance is not considered insufficient response.

B. Methotrexate and azathioprine use will count as 1 for the purposes of the number of failed treatments.

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

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

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

iii) Presence of at least 1 myositis specific (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.

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, leflunomide, IVIG, and rituximab.

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

i) Fulfilling 2013 ACR and European League Against Rheumatism classification criteria for SSc.

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

• SSc disease activity.

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

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

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.

• Recent or present clinically significant CNS pathology.

• 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.

Related Conditions & MeSH terms

• Autoimmune Diseases
• Idiopathic Inflammatory Myopathy
• Lupus Erythematosus, Systemic
• Muscular Diseases
• Myositis
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Lupus Erythematosus
• Systemic Sclerosis

Intervention

Drug:
• CC-97540
Specified dose on specified days
• Fludarabine
Specified dose on specified days
• Cyclophosphamide
Specified dose on specified days

Locations

Country	Name	City	State
Belgium	UZ Leuven	Leuven	Vlaams-Brabant
France	Hopital Claude Huriez - CHU de Lille	Lille
France	CHU Montpellier Lapeyronie Hospital	Montpellier	Hérault
France	Local Institution - 0040	Nice
France	Hôpital Saint-Louis	Paris
France	Local Institution - 0052	Paris
France	Local Institution - 0044	Pessac	Aquitaine
France	Centre Hospitalier Universitaire de Rennes - Hôpital Pontchaillou	Rennes
France	Local Institution - 0043	Strasbourg	Alsace
Germany	Charité Universitaetsmedizin Berlin - Campus Mitte	Berlin
Germany	Local Institution - 0047	Düsseldorf
Germany	Universitaetsklinikum Erlangen	Erlangen
Germany	Local Institution - 0042	Köln	Nordrhein-Westfalen
Germany	Local Institution - 0041	Leipzig	Sachsen
Germany	Local Institution - 0045	Magdeburg	Sachsen-Anhalt
Germany	Local Institution - 0049	Wuerzburg	Bayern
Italy	Local Institution - 0012	Roma	Lazio
Italy	Local Institution - 0023	Rozzano	Milano
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Barcelona [Barcelona]
Spain	Local Institution - 0021	Barcelona	Catalunya [Cataluña]
Spain	Local Institution - 0050	Cordoba
Spain	Local Institution - 0039	Málaga
Spain	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria
United States	Local Institution - 0031	Ann Arbor	Michigan
United States	Local Institution - 0035	Aurora	Colorado
United States	Local Institution - 0030	Baltimore	Maryland
United States	Local Institution - 0038	Boston	Massachusetts
United States	Local Institution - 0046	Boston	Massachusetts
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Local Institution - 0053	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Local Institution - 0027	Columbus	Ohio
United States	Local Institution - 0036	Dallas	Texas
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Local Institution - 0037	Detroit	Michigan
United States	Local Institution - 0029	Houston	Texas
United States	Local Institution - 0034	Houston	Texas
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Local Institution - 0048	New Haven	Connecticut
United States	Columbia University Irving Medical Center	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Local Institution - 0054	New York	New York
United States	NYU Langone Health	New York	New York
United States	Local Institution - 0028	Omaha	Nebraska
United States	Mayo Clinic in Rochester, Minnesota	Rochester	Minnesota
United States	Local Institution - 0010	Saint Louis	Missouri
United States	Swedish Medical Center	Seattle	Washington
United States	Atlantic Health System Overlook Medical Center	Summit	New Jersey
United States	Local Institution - 0033	Worcester	Massachusetts
United States	University of Massachusetts Chan Medical School	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Juno Therapeutics, Inc., a Bristol-Myers Squibb Company	Bristol-Myers Squibb Services Unlimited Company

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-emergent adverse events (AEs) in each indication.		Up to 2 years after CC-97540 infusion
Primary	Number of participants with serious AEs (SAEs) in each indication.		Up to 2 years after CC-97540 infusion
Primary	Number of participants with AEs of special interest (AESI) in each indication.		Up to 2 years after CC-97540 infusion
Primary	Number of participants with laboratory abnormalities in each indication.		Up to 2 years after CC-97540 infusion
Primary	Number of participants with Dose Limiting Toxicities (DLT) in each indication.		Up to 2 years after CC-97540 infusion
Primary	Recommended Phase 2 Dose (RP2D) of CC-97540 in each indication.		Up to 2 years after CC-97540 infusion
Secondary	Proportion of participants achieving definition of remission in SLE (DORIS) remission	SLE Cohort	At week 24
Secondary	Proportion of participants achieving Lupus Low Disease Activity State (LLDAS)	SLE Cohort	At week 24
Secondary	Change in proteinuria measured by urine protein creatinine ratio (UPCR)	SLE Cohort	At week 24
Secondary	Change in Health Assessment Questionnaire - Disability Index (HAQ-DI)		At week 24
Secondary	Proportion of participants achieving Myositis Response Criteria (MRC) Total Improvement Score (TIS) Major Response	IIM Cohort	At Week 24
Secondary	Change in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)	Only Dermatomyositis (DM) participants in the IIM Cohort	At Week 24
Secondary	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%)	IIM Cohort	At Week 24
Secondary	Proportion of participants achieving a minimal clinically important difference (MCID) of 24% change from baseline of the modified Rodnan Skin Score (mRSS)	SSc Cohort	At Week 24
Secondary	Participants with an improvement from baseline of the Revised Composite Response Index in Systemic Sclerosis (CRISS)	SSc Cohort	At Week 24
Secondary	The worsening of pulmonary function including FVC (>10% absolute), DLCO (>15% absolute decline) in participants with interstitial lung disease (ILD)	SSc Cohort	At Week 24
Secondary	Maximum observed blood concentration (Cmax)		Up to 2 years
Secondary	Time of maximum observed blood concentration (Tmax)		Up to 2 years
Secondary	Area under the blood concentration-time curve from time zero to 28 days after dosing (AUC(0-28D))		Up to 2 years

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting