AMG 634 / Amgen, Medicines Development for Global Health - LARVOL DELTA

A trial of two host-directed therapies in patients with drug-resistant tuberculosis (DRTB-HDT) (clinicaltrialsregister.eu) - P2 | N=330 | Sponsor: The Aurum Institute

New P2 trial • Dermatology • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4

A phosphodiesterase-4 inhibitor reduces lung inflammation and fibrosis in a hamster model of SARS-CoV-2 infection. (PubMed, Front Immunol) - "Cellular studies indicate a link between TNF-α and fibrotic remodeling during CC-11050 therapy. These findings suggest that CC-11050 may be a potential host-directed therapy to dampen inflammation and fibrosis in COVID-19 cases."

Journal • Preclinical • Acute Respiratory Distress Syndrome • Fibrosis • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • TNFA

Lung and blood early biomarkers for host-directed tuberculosis therapies: Secondary outcome measures from a randomized controlled trial. (PubMed, PLoS One) - "None of these early biomarkers correctly predicted HDT effects on inflammation or infection across all four experimental arms. Instead, they each appear to show highly specific responses related to HDT mechanisms of action."

Biomarker • Journal • Bronchiectasis • Fibrosis • Immunology • Infectious Disease • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pneumonia • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CRP

Adjunctive host-directed therapies for pulmonary tuberculosis: a prospective, open-label, phase 2, randomised controlled trial. (PubMed, Lancet Respir Med) - P2 | "CC-11050 and everolimus were safe and reasonably well tolerated as adjunctive therapies for tuberculosis, and analysis of preliminary efficacy suggests they might also enhance the recovery of FEV, a key measure of lung function and predictor of all-cause mortality. Further studies of these candidates are warranted."

Clinical • Journal • P2 data • Hematological Disorders • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammatory Arthritis • Liver Failure • Respiratory Diseases • Septic Shock • Seronegative Spondyloarthropathies • Thrombocytopenia • Tuberculosis

Amgen Licenses AMG 634, An Investigational Treatment For Tuberculosis And Leprosy, To Medicines Development for Global Health (PRNewswire) - "Amgen (NASDAQ:AMGN) and Medicines Development for Global Health (MDGH)...today announced that the companies have entered into a license agreement for AMG 634, a phosphodiesterase type 4 (PDE4) inhibitor being investigated for the treatment of...erythema nodosum leprosum (ENL)...Under the terms of the agreement, MDGH will assume full responsibility for the further development and commercialization of AMG 634....Amgen will continue to support the two Phase 2 clinical trials in ENL and TB set to begin in 2021 by providing study drug to both studies and funding the ENL study."

Licensing / partnership • New P2 trial • Immunology

A Study to Evaluate the Safety, Tolerability Pharmacokinetics, and Pharmacodynamics of a New Spray Dried Dispersion (SDD) Formulation of CC-11050 After Single Dose of CC-11050 and to Evaluate the Pharmacokinetics of CC-11050 Under Fasted and Fed Conditions and After Coadministration With Omeprazole (clinicaltrials.gov) - P1; N=44; Completed; Sponsor: Celgene; Recruiting ➔ Completed

Clinical • Trial completion

A Study to Evaluate the Safety, Tolerability Pharmacokinetics, and Pharmacodynamics of a New Spray Dried Dispersion (SDD) Formulation of CC-11050 After Single Dose of CC-11050 and to Evaluate the Pharmacokinetics of CC-11050 Under Fasted and Fed Conditions and After Coadministration With Omeprazole (clinicaltrials.gov) - P1; N=42; Recruiting; Sponsor: Celgene

Clinical • New P1 trial

"CC-11050 is the other PDE4i $CELG had besides Otezla apremilast. I am quite sure $CELG discontinued development of CC-11050 many years ago." (@jq1234t)

A Phase I, Randomized, Controlled Clinical Study of CC-11050 in People Living With HIV With Suppressed Plasma Viremia on Antiretroviral Therapy (APHRODITE). (PubMed, Open Forum Infect Dis) - "CC-11050 was well tolerated in PLWH, without affecting CD4 counts or plasma viremia, and led to a decrease in NK cells and plasma IL-8 level after 12-weeks of administration. Further study will be needed to elucidate the efficacy of CC-11050 as potential anti-inflammatory adjuvant strategy in HIV."

Clinical • Journal

Preliminary Results of an Experimental Medicine Trial of Adjunctive Host-Directed Therapy in Adults with Moderately or Far-Advanced Rifampin-Susceptible Pulmonary Tuberculosis (ATS 2019) - "Methods : 200 adult HIV-1-uninfected patients with rifampin-susceptible pulmonary tuberculosis (moderately or far-advanced by chest X-ray) were randomly assigned (40 per arm) to CC-11050 (type 4 phosphodiesterase inhibitor, 200mg BID), everolimus (mTOR inhibitor, 0.5mg QD), auranofin (oral gold salt, 6mg QD), vitamin D (ergocalciferol, 5mg initially, then 2.5mg on days 28 and 56), or control, for the first 4 months of rifabutin-substituted standard treatment (2HRbZE/4HRb). Adjunctive TB HDTs appear likely to reach the objectives of preserving lung function and accelerating eradication of infection. Results from this trial can help inform the design of future studies. Funding: Bill and Melinda Gates foundation"

Clinical

Streptomyces cadmiisoli sp. nov., a novel actinomycete isolated from cadmium-contaminated soil. (PubMed, Int J Syst Evol Microbiol) - "nov. is proposed, with strain ZFG47 (CICC 11050=JCM 32897) as the type strain."

Journal

A phase 1, randomized, controlled clinical study of CC-11050 in people living with HIV with suppressed plasma viremia on antiretroviral therapy (APHRODITE) (AAI 2019) - "CC-11050 was well tolerated in HIV+ participants without affecting controlled viremia. CC-11050 had an effect on innate immune mechanisms, by decreasing NK cells and IL-8 level and increasing intermediate monocytes. Further study is needed to elucidate the efficacy of CC-11050 as potential anti-inflammatory adjuvant strategy in HIV"

Clinical • P1 data

CC-11050 Trial in Nepalese Patients With Erythema Nodosum Leprosum (clinicaltrials.gov) - P2; N=50; Recruiting; Sponsor: The Leprosy Mission Nepal

Clinical • New P2 trial

TBHDT: TB Host Directed Therapy (clinicaltrials.gov) - P2; N=200; Active, not recruiting; Sponsor: The Aurum Institute NPC; Recruiting ➔ Active, not recruiting

Biomarker • Clinical • Enrollment closed