BMS-986371 / BMS - LARVOL DELTA

A Phase 2 Multicenter, Randomized, Double-Blinded, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of a Mitogen-activated Protein Kinase-Activated Protein Kinase 2 (MK2) Inhibitor in Active Ankylosing Spondylitis (ACR Convergence 2024) - "The study was prematurely terminated for futility. The termination was not related to any observed adverse events, or perceived safety findings associated with CC-99677."

Clinical • P2 data • Ankylosing Spondylitis • Back Pain • Immunology • Inflammatory Arthritis • Musculoskeletal Pain • Pain • Rheumatology • Seronegative Spondyloarthropathies • CRP • IL17A • IL6 • MAPKAPK2 • TNFA

A Pilot Study to Assess the Suitability of Riboflavin as A Surrogate Marker of Breast Cancer Resistance Protein (BCRP) in Healthy Participants. (PubMed, J Pharmacol Exp Ther) - "The effects of BMS-986371, a potent in vitro inhibitor of BCRP (IC 0.40 µM), on the pharmacokinetics of riboflavin, isobutyryl carnitine, and arginine were then examined in healthy male adults (N = 14 or 16) following oral administration of methotrexate (MTX) (7.5 mg) and enteric coated (EC) sulfasalazine (SSZ) (1,000 mg) alone or in combination with BMS-986371 (150 mg). Oral administration of BMS-986371 increased the AUCs of rosuvastatin and immediate-release (IR) SSZ to 1.38- and 1.51-fold , respectively, and significantly increased AUC(0-4h), AUC(0-24h), and C of riboflavin by 1.25-, 1.14-, and 1.11-fold (P-values of 0.003, 0.009, and 0.025, respectively) compared to the MTX/SSZ EC alone group...For the first time, the value of leveraging the substrate of BCRP with acceptable prediction performance in clinical studies is shown. Additional clinical investigations with known BCRP inhibitors are needed to fully validate and showcase the utility of this biomarker."

Journal • Breast Cancer • Metabolic Disorders • Oncology • Solid Tumor

AS SpA axSpA: A Study of CC-99677 in Participants With Active Ankylosing Spondylitis (clinicaltrials.gov) - P2 | N=167 | Terminated | Sponsor: Celgene | N=256 ➔ 167 | Trial completion date: Feb 2024 ➔ Feb 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Nov 2023 ➔ Feb 2023; The study has been terminated due to Non-Safety reasons because of lack of efficacy in the short-term acute phase.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Ankylosing Spondylitis • Immunology • Inflammatory Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CRP • IL17A

A Study to Assess the Effects of BMS-986371 on the Drug Levels of Methotrexate in the Presence and Absence of Sulfasalazine (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Completed

Trial completion

AS SpA axSpA: A Study of CC-99677 in Participants With Active Ankylosing Spondylitis (clinicaltrials.gov) - P2 | N=256 | Active, not recruiting | Sponsor: Celgene | Recruiting ➔ Active, not recruiting

Enrollment closed • Ankylosing Spondylitis • Immunology • Inflammatory Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CRP • IL17A

A Study to Evaluate the Drug Levels of [14C]CC-99677 in Healthy Male Participants (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Completed

Trial completion

AS SpA axSpA: A Study of CC-99677 in Participants With Active Ankylosing Spondylitis (clinicaltrials.gov) - P2; N=256; Recruiting; Sponsor: Celgene; Phase classification: P2a ➔ P2

Clinical • Phase classification • Ankylosing Spondylitis • Immunology • Inflammatory Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CRP • IL17A • MRI

A Study to Assess the Effects of BMS-986371 on the Drug Levels of Methotrexate in the Presence and Absence of Sulfasalazine (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open

CC-99677, a novel, oral, selective covalent MK2 inhibitor, sustainably reduces pro-inflammatory cytokine production. (PubMed, Arthritis Res Ther) - P1 | "CC-99677 inhibition of MK2 is a promising approach for the treatment of inflammatory diseases and may overcome the limitations of p38 MAPK inhibition."

Journal • Ankylosing Spondylitis • Immunology • Inflammation • Inflammatory Arthritis • Oncology • Rheumatology • Seronegative Spondyloarthropathies • Spondylarthritis • IL17A • IL6 • TNFA

A Study to Assess the Effects of BMS-986371 on the Drug Levels of Methotrexate in the Presence and Absence of Sulfasalazine (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P1 trial

Discovery of CC-99677, a Selective Targeted Covalent MAPKAPK2 (MK2) Inhibitor for Autoimmune Disorders. (PubMed, Transl Res) - "Single doses, 3 to 400 mg, in healthy human volunteers show linear pharmacokinetics and apparent sustained tumor necrosis factor-α inhibition, with a favorable safety profile. These results support further development of CC-99677 for autoimmune diseases like ankylosing spondylitis."

Journal • Ankylosing Spondylitis • Immunology • Inflammation • Inflammatory Arthritis • Oncology • Rheumatology • Seronegative Spondyloarthropathies • MAPKAPK2

Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CC-99677 in Healthy Adult Japanese Participants. (clinicaltrials.gov) - P1 | N=25 | Completed | Sponsor: Celgene | Not yet recruiting ➔ Completed

Trial completion

A Study to Evaluate the Drug Levels of [14C]CC-99677 in Healthy Male Participants (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P1 trial

[VIRTUAL] CC-99677, a Novel, Selective, Oral MK2 Inhibitor, Sustainably Reduces Pro-inflammatory Cytokine Production and Ameliorates Inflammation in the Mannan-Induced Murine Model of Psoriasis and Psoriatic Arthritis (ACR-CONVERGENCE 2021) - "CC-99677 is an MK2 inhibitor that exhibits sustained inhibition of TNF in vitro and effectively reduces TNF production in stimulated immune cells from patients with PsA. In the in vivo MIP model of psoriasis and PsA, MK2 inhibition was efficacious in reducing skin and joint inflammation, reflected in a dose-dependent reduction in PsASI score. These data extend previous results demonstrating reduction in cytokine production in stimulated PBMCs from patients with AS and efficacy in the rat HLA-B27 transgenic model of AS.5 Thus, our in vitro and in vivo data support investigating CC-99677 in clinical studies planned in patients with spondyloarthritis."

Preclinical • Ankylosing Spondylitis • Dermatology • Immunology • Inflammation • Inflammatory Arthritis • Psoriasis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Spondylarthritis • IL17A • IL6 • MAPKAPK2

[VIRTUAL] CC-99677: A Novel, Oral, Selective MK2 Inhibitor with Sustainable Multi-Cytokine Inhibition for the Treatment of Ankylosing Spondylitis and Other Inflammatory Diseases (ACR-CONVERGENCE 2021) - P1 | "Administration of CC-99677 was safe and well tolerated, resulted in linear PK, and demonstrated sustained reduction of ex vivo whole blood TNF-α, IL-6, and chemokine synthesis. The lack of tachyphylaxis in human cells exposed to CC-99677, compared with previous disappointing results targeting the p38 axis, is encouraging. Thus, CC-99677 inhibition of MK2 is a promising approach for the treatment of inflammatory diseases."

Ankylosing Spondylitis • Immunology • Inflammation • Inflammatory Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Spondylarthritis • IL17A • IL6 • MAPKAPK2 • TNFA

Bristol Myers Squibb Data at ACR Convergence 2021 Illustrate Scientific Advances for Immune-Mediated Rheumatic Diseases (Businesswire) - P2, N=203; NCT03881059; Sponsor: Bristol-Myers Squibb; "Bristol Myers Squibb...announced data from 29 company-sponsored presentations across Orencia, deucravacitinib and pipeline assets will be presented at the American College of Rheumatology (ACR) Convergence 2021, taking place virtually November 3-10, 2021...Biomarker analyses from a Phase 2 study that showed deucravacitinib suppressed blood biomarkers of the IL-23/IL-17 and IFN-1 pathways and key markers of joint damage, concomitant with clinical symptom improvements in patients with psoriatic arthritis in comparison with placebo (abstract number 0490). There were no clinically meaningful changes in mean levels of serum cholesterol, creatinine, neutrophils and platelets over time with deucravacitinib treatment...Additional data will also be presented from Bristol Myers Squibb’s immunology pipeline...CC-99677 (MK2 inhibitor) data in ankylosing spondylitis, psoriasis and psoriatic arthritis."

P2 data • Immunology • Psoriasis • Psoriatic Arthritis

Bristol Myers Squibb Data at ACR Convergence 2021 Illustrate Scientific Advances for Immune-Mediated Rheumatic Diseases (Businesswire) - “Bristol Myers Squibb...announced data from 29 company-sponsored presentations across Orencia, deucravacitinib and pipeline assets will be presented at the American College of Rheumatology (ACR) Convergence 2021, taking place virtually November 3-10, 2021….Additional data will also be presented from Bristol Myers Squibb’s immunology pipeline, including iberdomide and BMS-986256 (TLR7/8 inhibitor) data in lupus and CC-99677 (MK2 inhibitor) data in ankylosing spondylitis, psoriasis and psoriatic arthritis.”

Clinical data • Ankylosing Spondylitis • Immunology • Lupus • Rheumatoid Arthritis • Systemic Lupus Erythematosus

A Study to Evaluate Effects of CC-99677 on the Pharmacokinetics of an Oral Contraceptive in Healthy Female Participants (clinicaltrials.gov) - P1; N=28; Completed; Sponsor: Celgene; Recruiting ➔ Completed

Clinical • Trial completion

AS SpA axSpA: A Study of CC-99677 in Participants With Active Ankylosing Spondylitis (clinicaltrials.gov) - P2a; N=256; Recruiting; Sponsor: Celgene; Not yet recruiting ➔ Recruiting; Phase classification: P2 ➔ P2a; Trial primary completion date: Jan 2023 ➔ Nov 2023

Clinical • Enrollment open • Phase classification • Trial primary completion date • Ankylosing Spondylitis • Immunology • Inflammatory Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CRP • IL17A • MRI

A Study to Evaluate Potential Cytochrome P450 and Transporter Protein Interactions With CC-99677 (clinicaltrials.gov) - P1; N=48; Completed; Sponsor: Celgene; Recruiting ➔ Completed

Trial completion

Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CC-99677 in Healthy Adult Japanese Participants. (clinicaltrials.gov) - P1; N=24; Not yet recruiting; Sponsor: Celgene

Clinical • New P1 trial

AS SpA axSpA: A Study of CC-99677 in Participants With Active Ankylosing Spondylitis (clinicaltrials.gov) - P2; N=256; Not yet recruiting; Sponsor: Celgene

Clinical • New P2 trial • Ankylosing Spondylitis • Immunology • Inflammatory Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CRP • IL17A • MRI

A Study to Evaluate Effects of CC-99677 on the Pharmacokinetics of an Oral Contraceptive in Healthy Female Participants (clinicaltrials.gov) - P1; N=28; Recruiting; Sponsor: Celgene

Clinical • New P1 trial

A Study to Evaluate Potential Cytochrome P450 and Transporter Protein Interactions With CC-99677 (clinicaltrials.gov) - P1; N=48; Recruiting; Sponsor: Celgene; Not yet recruiting ➔ Recruiting; Trial completion date: Oct 2020 ➔ Apr 2021; Initiation date: Feb 2020 ➔ Sep 2020; Trial primary completion date: Sep 2020 ➔ Apr 2021

Clinical • Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of CC-99677 in Healthy Adult Subjects (clinicaltrials.gov) - P1; N=97; Completed; Sponsor: Celgene; Recruiting ➔ Completed; Trial completion date: Nov 2019 ➔ Jul 2019; Trial primary completion date: Nov 2019 ➔ Jul 2019

Clinical • Trial completion • Trial completion date • Trial primary completion date