A Multiple Arm, Multiple Stage, Phase 2, OL, Randomized, Controlled Trial to Evaluate 4 Treatment Regimens of SQ109, Increased Doses of Rifampicin, and Moxifloxacin in Adults With Newly Diagnosed, Smear-positive Pulmonary Tuberculosis

This study is a multiple-arm, multiple-stage (MAMS), phase 2, open label, randomized, controlled clinical trial that will compare the efficacy and safety of four experimental four drug regimens with a standard control regimen in patients with smear positive, pulmonary tuberculosis (TB). Patients will be randomly allocated to the control or one of the four experimental regimens in the ratio 2:1:1:1:1. Experimental regimens will be given for 12 weeks. Thereafter, participants in the experimental arms will receive continuation phase treatment for 14 weeks containing standard-dose rifampicin and isoniazid. All participants will receive 25 mg of vitamin B6 (pyridoxine) with every dose of INH to prevent INH-related neuropathy. Interim analyses will be conducted during the trial for efficacy, with the aim of identifying experimental arms that perform below a pre-specified efficacy threshold; these arms will then be stopped from further recruitment.
Following the first scheduled interim analysis on March 3rd, the Trial Steering Committee (TSC) followed a recommendation of the independent data monitoring committee (IDMC) and has stopped the enrolment into two of the arms in the MAMS-TB trial: HRZQ and HR20ZQ, based on these arms not meeting the pre-specified gain in efficacy over control. Importantly, there was no safety concern that prompted stopping recruitment to these arms. They recommended that recruitment to arm 2 (HRZQ) and 3 (HR20ZQ) be terminated as there was insufficient evidence that these regimens could shorten treatment. Importantly, there was no evidence that either arm was inferior to standard treatment (the control arm) with regards to efficacy. There was, however, sufficient evidence that the other intervention arms HR35ZE and HR20ZM could shorten treatment to continue enrolling patients.

Start Date01 Apr 2013

Sponsor / Collaborator

Ludwig-Maximilians-Universität München

[+4]

PACTR201205000383208

/ Unknown statusPhase 2IIT

A multiple arm, multiple stage (MAMS), phase 2, open label, randomized, controlled clinical trial to evaluate four treatment regimens including SQ109, two increased doses of rifampicin, and moxifloxacin in adult subjects with newly diagnosed, smear¿positive pulmonary tuberculosis

Start Date11 Jan 2013

Sponsor / Collaborator-

NCT01252108

/ WithdrawnPhase 2

Phase 2A Open-label Study to Evaluate Safety, Tolerability, and Antimicrobial Activity of Single, Daily Doses of SQ109 in Urea Breath Test Positive Volunteers

Helicobacter pylori infection of the gastric epithelium is the most common bacterial infection worldwide. Its global prevalence is estimated at 50%, though the burden falls disproportionately on the developing world, where the prevalence in some areas is 80%. H. pylori infection is generally acquired during childhood, and without specific antibiotic treatment can persist for life. The infection is generally clinically asymptomatic during childhood, and even in adulthood 80-90% of infected individuals will remain asymptomatic (although they may transmit the bacteria).
SQ109 is a new, small molecule antibiotic with characteristics that make it particularly attractive to evaluate against H. pylori. In brief, SQ109 is orally bioavailable, acid-stable, has in vitro activity against H. pylori and achieves high intracellular concentration (which may be important to effect bacterial eradication).
Based on the antimicrobial activity and clinical safety, SQ109 will be evaluated in this clinical trial to assess safety and antimicrobial activity in adults infected with H. pylori. Data from this study will help determine whether larger safety and efficacy studies in individuals with H. pylori-associated duodenal ulcer disease are warranted.

Start Date01 Mar 2012

Sponsor / Collaborator

Sequella, Inc.

100 Clinical Results associated with SQ-109

100 Translational Medicine associated with SQ-109

100 Patents (Medical) associated with SQ-109

188

Literatures (Medical) associated with SQ-109

01 Oct 2025·Computational Biology and Chemistry

Exploring spirocyclic isoquinoline-piperidine compounds in tuberculosis therapy: ADMET profiling, docking, DFT, MD simulations, and MMGBSA analysis

Article

Author: Bellapukonda, Sri Mounika ; Bandela, Rani ; Bhandari, Vasundhra ; Kumar, Pardeep ; Oubella, Ali ; Singampalli, Anuradha ; Singothu, Siva ; Enneiymy, Mohamed ; AlAjm, Mohamed F ; Yaddanapudi, Venkata Madhavi ; Nanduri, Srinivas

Tuberculosis remains a global health challenge due to drug-resistant strains. MmpL3 inhibitors have emerged as promising anti-tubercular agents, and their clinical development has been hindered by poor microsomal stability. This study computationally designed and screened 40 spirocyclic analogs, and compared them with ICA38 and SQ109. In silico analyses, including docking, MD simulations, and DFT calculations, were conducted to assess their potential as anti-tubercular agents, highlighting promising candidates for further development. Docking studies using Glide software identified C21 (3,4- dichloro derivative) and C20 (5-chloro derivative) as promising candidates, exhibiting binding scores of -9.79 kcal/mol and -9.64 kcal/mol, respectively. Both compounds interacted with the active site residue Asp645 via hydrogen bonding and also formed a hydrophobic interaction. DFT results revealed that C21 displayed the balanced chemical reactivity, characterized by high dipole moment (3.63D), an optimal energy gap (0.18752 eV), softness and hardness (η = 0.09376 eV, σ = 10.666 eV⁻¹), high electron affinity (0.02305 eV), high electronegativity (0.11681 eV) and high ionization potential (0.21057 cV). On the other hand, C20 exhibited similar electronic properties with marginal differences than C21. MD simulations showed C21 and C20's stability (RMSD 2.4 Å and 2.2 Å, RMSF <2.5 Å), indicating improved Arg344-Leu354 stability. Additionally, C21 and C20 maintained Asp645 interactions (91 %, 97 %) and showed strong binding with free energy values (MMGBSA: -72.23, -66.50 kcal/mol). These findings highlight the efficiency of the compounds C21 and C20 with strong binding affinity, favorable stability, and optimal electronic properties, making them promising candidates for further development of next-generation MmpL3 inhibitors.

11 Apr 2025·ACS Infectious Diseases

Characterization of the Orphan Cytochrome P450 CYP135B1 from Mycobacterium tuberculosis: Involvement in Metabolism but Not in the Antibacterial Activity of the Antitubercular Drug SQ109

Article

Author: Poch, Olivier ; Pionneau, Cédric ; Clodic, Gilles ; Sachon, Emmanuelle ; Pietrancosta, Nicolas ; Boucher, Jean-Luc ; Mayer, Claudine ; Veyron-Churlet, Romain ; Aubry, Alexandra ; Sadowski, Elodie ; Matheron, Lucrèce

The rise of multidrug-resistant tuberculosis (TB) has increased the need for new antitubercular (anti-TB) drugs and the identification of novel drug targets. One promising target is Mycobacterium tuberculosis (Mtb) cytochrome P450 enzymes (P450s). This study focuses on the characterization of CYP135B1, a prevalent Mtb P450. Using a combination of microbiology, genomics, bioinformatics, docking, spectroscopy, and mass spectrometry, researchers successfully expressed, purified, and characterized CYP135B1. A 3D model was built with AlphaFold 3. The enzyme displayed typical features of P450 proteins and showed strong binding to imidazole derivatives. Notably, CYP135B1 metabolized the anti-TB drug SQ109 by inserting oxygen into its geranyl moiety in a manner distinct from CYP124A1. However, genetic studies using a ΔCYP135B1 mutant strain revealed that CYP135B1 is not required for SQ109's antibacterial activity, as its deletion did not affect drug efficacy despite CYP135B1 metabolizes SQ109.

01 Apr 2025·Archiv der Pharmazie

Synthesis, Antituberculosis Evaluation and Structure–Activity Relationships of New SQ109 Analogs

Article

Author: de Souza, Marcus Vinícius Nora ; do Carmo Ferreira, Frederico Henrique ; Saraiva, Mauricio Frota ; da Silva Lourenço, Maria Cristina ; Costa, Luiz Antônio Sodré ; dos Reis, Dijovani Batista ; Linhares, Emily Pacelli Moreira ; de Almeida, Mauro Vieira ; dos Santos e Silva, Gabriel ; Ávila, Eloah Pereira

ABSTRACTTuberculosis (TB) is a bacterial disease that poses significant challenges in its treatment. It requires prolonged use of high doses of medication, which can lead to various side effects. These side effects often contribute to low patient adherence to treatment, thereby increasing the risk of developing drug‐resistant strains. The SQ109 is a second‐generation agent developed from ethambutol that has been emerging as a promising TB agent. The functionalization of its skeleton appears as a strategy to improve the physicochemical and biological properties. Hence, we report the synthesis of functionalized SQ109 scaffolds, the in vitro evaluation against Mycobacterium tuberculosis H37Rv strains, molecular docking simulations, and molecular dynamics of the interactions with the target membrane protein.

News (Medical) associated with SQ-109

29 Oct 2008

·www.biospace.com

Sequella, Inc. Presents Data on Synergy Between Investigational New TB Drugs SQ109 and TMC207

Study results to be presented at 2008 ICAAC/IDSA Joint Meeting ROCKVILLE, Md., Oct. 28 /PRNewswire/ -- Sequella, Inc., a clinical-stage biopharmaceutical company focused on commercializing products to treat infectious diseases of epidemic potential, announces the successful demonstration of synergistic activities and improvement of minimal inhibitory concentration (MIC) resulting from in vitro combination studies of Sequella lead TB drug candidate, SQ109, and Tibotec's lead TB drug candidate, TMC207. Both drug candidates are currently undergoing human clinical studies. Results from these studies were presented on October 28th at the Interscience Conference on Anti-Microbial Agents and Chemotherapeutics (ICAAC) and Infectious Disease Society of America (IDSA) joint meeting in Washington, DC. The collaboration between Sequella and Tibotec was designed to investigate in vitro interactions of SQ109 for synergistic, additive, or antagonistic activity in the presence of TMC207, using a number of clinical and laboratory strains of both drug sensitive and drug resistant M. tuberculosis (MTB). In vitro interactions investigated included synergy studies, rate of killing, post antibiotic effect and intracellular activity against MTB in macrophages. There were no antagonistic activities observed in any combination studies. SQ109 and TMC207 in combination were either synergistic or additive with the various MTB strains and showed increased rate of killing, enhanced post antibiotic effect and intracellular killing activity. Results showed that the SQ109 and TMC207 drug combination was extraordinary potent, with greater than 90% kill of MTB as early as 1 day after drug combination exposure. Dr. Carol Nacy, CEO of Sequella said, "We are very pleased to be collaborating with Tibotec, a world renowned product development organization, and we look forward to our continuing partnership to examine these important drug synergies in animal models of TB." The next step of the collaboration will be to complete a series of in vivo studies in animal models of TB, currently underway. About SQ109 The company's lead drug candidate, SQ109, completing Phase I clinical trials, is a new diamine antibiotic that could replace one or more of the current first-line anti-tuberculosis drugs to simplify or shorten therapy. SQ109 was granted U.S. FDA Fast Track and FDA/EMEA Orphan Drug Designation in 2007. About Sequella Sequella is a clinical stage biopharmaceutical company focused on commercializing improved treatments for infectious diseases of epidemic potential. The company leverages its global influence, R&D platforms and infectious disease expertise to proactively address emerging health threats. Through focused execution, clear commercialization pathways, and strategic partnerships, Sequella intends to commercialize a broad product portfolio designed to treat global health threats with significant market opportunity. Forward-Looking Statement This press release contains forward-looking statements that are subject to risks and uncertainties, and includes statements that are not historical facts. Actual results could differ significantly from results discussed. Sequella disclaims any intent or obligation to update forward-looking statements, except as required by law. CONTACT: Alicia Moran, +1-410-991-7027, for Sequella, Inc. Web site:

CollaborateSmall molecular drugAntibodyOrphan DrugFast Track

100 Deals associated with SQ-109

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KEGG	Wiki	ATC	Drug Bank
-	SQ-109	-	DB05186

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Pulmonary Tuberculosis	Phase 3	Russia	Infectex LLC	29 Aug 2022
Helicobacter pylori infection	Phase 2	-	Sequella, Inc.	01 Mar 2012
Tuberculosis	Preclinical	United States	Sequella, Inc.	01 Sep 2006

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01785186 (CTgov)	Phase 2	Pulmonary Tuberculosis	365	pyridoxine+Ethambutol+Rifampicin+Isoniazid+Pyrazinamide (Arm 1 (R35))	fkfjyaevme(tmtadhpysl) = xmmrnxzzmo qugntocmkm (xcjofxsonx, bjkkjqopfv - evuqzjrgjx) View more	-	20 Sep 2017
				SQ109+Rifampicin+pyridoxine+Isoniazid+Pyrazinamide (HRZQ)	fkfjyaevme(tmtadhpysl) = cxsusrxioq qugntocmkm (xcjofxsonx, geudvdnmwd - ubmbydlwep) View more

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