EBA, Safety and Tolerability of Sanfetrinem Cilexetil

NCT05388448 | Completed Phase 2 DMC

• 1 other identifier: TASK-009-SANF
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the 2-week bactericidal activity, pharmacokinetics, safety and tolerability of sanfetrinem cilexetil in participants with rifampicin-susceptible pulmonary tuberculosis.

Conditions

Tuberculosis, Pulmonary

Keywords

tuberculosis; early bactericidal activity; bedaquiline; delamanid

Outcome Measures

Primary Outcomes (1)

• Rate of change in mycobacterium tuberculosis (Mtb) load in sputum from pre-treatment to Day 14 on-treatment, based on colony forming unit (CFU) count on solid culture media (7H11 agar plates)

  Early bactericidal activity (EBA) will be determined, per treatment arm, as the rate of change in log10 CFU count per ml sputum over the treatment period day 0 to day 14, and described using linear, bi-linear or non-linear regression of log10CFU count over time and relation to drug exposure.

  14 days

Secondary Outcomes (2)

• Rate of change in mycobacterium tuberculosis (Mtb) load in sputum from pre-treatment to Day 14 on-treatment, based on time to positive (TTP) culture in the BACTEC MGIT 960 liquid culture system

  14 days

• Number of patients with abnormal safety and tolerability findings following the study regimens, administered for 14 days

  14 days

Study Arms (3)

Sanfetrinem cilexetil 1.6 gram 12 hourly

EXPERIMENTAL

Sanfetrinem cilexetil 1.6g will be given orally 12 hourly for 14 consecutive days.

Drug: Sanfetrinem Cilexetil

Rifampicin 35 mg/kg once daily

EXPERIMENTAL

Rifampicin 35 mg/kg will be given orally once daily for 14 consecutive days.

Drug: Rifampicin

Sanfetrinem cilexetil 2.4 gram once daily

EXPERIMENTAL

Sanfetrinem cilexetil 2.4 g will be given orally daily for 14 consecutive days.

Drug: Sanfetrinem Cilexetil

Interventions

Sanfetrinem Cilexetil DRUG

Sanfetrinem cilexetil powder, weighed for dose and administered as a suspension in water. Amx/CA 250/125 mg tablets Rifampicin 150 mg, 300 mg and 600 mg tablets or capsules

Also known as: Compound number GV118819

Sanfetrinem cilexetil 1.6 gram 12 hourly; Sanfetrinem cilexetil 2.4 gram once daily

Rifampicin DRUG

Rifampicin will be administered at a dose of 35 mg/kg once daily for 14 days with or without sanfetrinem cilexetil.

Also known as: Rifadin

Rifampicin 35 mg/kg once daily

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are required to meet all of the following criteria in order to be randomized.
• Provide written, informed consent prior to all trial-related procedures.
• Male or female, aged between 18 and 65 years, inclusive.
• Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
• Newly diagnosed, previously untreated, rifampicin-susceptible pulmonary TB.
• A chest X-ray picture taken at screening which, in the opinion of the investigator, is consistent with TB.
• Sputum positive on direct microscopy for acid-fast bacilli on at least one sputum sample (at least 1+ on the IUATLD/WHO scale) or GeneXpert cycle threshold of medium or high.
• Ability to produce an adequate volume of sputum as estimated from an overnight sputum collection sample (estimated 10 ml or more).
• Be of non-childbearing potential or using effective methods of birth control, as defined below:
• Non-childbearing potential:
• Female participant/ female sexual partner - bilateral oophorectomy
• bilateral tubal ligation
• hysterectomy
• postmenopausal with no menses for at least 12 consecutive months Male participant/ male sexual partner - vasectomy
• bilateral orchidectomy more than three months prior to screening

You may not qualify if:

• Participants will be excluded from participation if they fulfil any of the following criteria.
• Evidence of clinically significant conditions or findings, other than TB, that might compromise safety or the interpretation of trial endpoints, per discretion of the investigator.
• Poor general condition where any delay in treatment cannot be tolerated per discretion of the investigator.
• Clinically significant evidence of extrathoracic TB, as judged by the investigator.
• History of allergy to any of the trial IP/s or related substances i.e. β-lactams and penicillin, as confirmed by the clinical judgement of the investigator.
• Alcohol or drug abuse, that in the opinion of the investigator, is sufficient to compromise the safety or cooperation of the participant.
• HIV positive ONLY IF:
• CD4 \< 250cells/mm3
• On ART
• Participation in other clinical studies with investigational agents within 8 weeks prior to trial start (with the exception of COVID-19 vaccines).
• Female participant who is pregnant, breast-feeding, or planning to conceive a child within the anticipated period of trial participation. Male participant planning to conceive a child within the anticipated period of participating in the trial.
• Treatment received with any drug active against M.tb (including but not limited to isoniazid, ethambutol, amikacin, cycloserine, fluoroquinolones, rifabutin, rifampicin, streptomycin, kanamycin, para-aminosalicylic acid, rifapentine, pyrazinamide, thioacetazone, capreomycin, thioamides), or with immunosuppressive medications such as TNF-alpha inhibitors within 2 weeks prior to screening, or systemic corticosteroids for more than 7 days within 2 weeks prior to screening.
• Participants with the following toxicities at screening as defined by the enhanced CTCEA toxicity table
• creatinine \>1.5 times upper limit of normal \[ULN\];
• haemoglobin \<8.0 g/dL;

Sponsors & Collaborators

• TASK Applied Science: lead
• GlaxoSmithKline: collaborator
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator

Study Sites (1)

TASK Clinical Research Centre

Cape Town, Western Cape, 7530, South Africa

Location

Related Publications (2)

• Ramon-Garcia S, Gonzalez Del Rio R, Arenaz-Callao MP, Boshoff HI, Rullas J, Anca S, Cacho Izquierdo M, Porras de Francisco E, Perez Herran E, Santos-Villarejo A, Mendoza-Losana A, Ferrer-Bazaga S, Thompson CJ, Barros Aguirre D, Bates RH. Sanfetrinem, an oral beta-lactam antibiotic repurposed for the treatment of tuberculosis. Drug Resist Updat. 2025 May;80:101213. doi: 10.1016/j.drup.2025.101213. Epub 2025 Feb 15.

  PMID: 40020440 DERIVED

• Ramon-Garcia S, Del Rio RG, Arenaz-Callao MP, Boshoff H, Rullas J, Anca S, Izquierdo MC, de Francisco EP, Herran EP, Santos-Villarejo A, Mendoza-Losana A, Ferrer-Bazaga S, Thompson CJ, Aguirre DB, Bates RH. Sanfetrinem, an oral beta-lactam antibiotic repurposed for the treatment of tuberculosis. bioRxiv [Preprint]. 2024 Oct 10:2024.10.10.617558. doi: 10.1101/2024.10.10.617558.

  PMID: 39803560 DERIVED

Related Links

• TASK Homepage - clinical research institute and social enterprise

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis

Interventions

sanfetrinem cilexetil; Rifampin

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Laboratory personnel are blinded to treatment arm
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Approximately 51 participants (3 groups of approximately 15 participants receiving IP including replacements in Stage 1) will be enrolled. 26 participants were enrolled in stage 1 and 25 are planned to be enrolled in stage 2. Participants will be between 18 and 65 years old (inclusive), with newly diagnosed, smear or Xpert MTB/RIF-positive, rifampicin susceptible pulmonary TB.

Study Record Dates

• First Submitted: January 25, 2022
• First Posted: May 24, 2022
• Study Start: April 21, 2022
• Primary Completion: August 19, 2024
• Study Completion: August 19, 2024
• Last Updated: February 21, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)