Tuberculosis, PulmonaryPhase 2NCT05388448
EBA, Safety and Tolerability of Sanfetrinem Cilexetil
A Phase 2 study testing Sanfetrinem Cilexetil and Rifampicin in people with Tuberculosis, Pulmonary, run by TASK Applied Science at 1 site in South Africa.
Trial summary
To evaluate the 2-week bactericidal activity, pharmacokinetics, safety and tolerability of sanfetrinem cilexetil in participants with rifampicin-susceptible pulmonary tuberculosis. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Tuberculosis, Pulmonary
- What is being tested?
- Sanfetrinem Cilexetil and Rifampicin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteSouth Africa
- Study dates
- 21 Apr 2022to 19 Aug 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 19Show fewer
- 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
- Effective birth control methods:
- Participant is not heterosexually active or practicing sexual abstinence
- Double barrier method which can include a male condom, diaphragm, cervical cap, or female condom (male and female condoms should not be used together); or
- Barrier method combined with hormone-based contraceptives or an intra-uterine device for the female partner.
Who cannot join
- 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.
Show all 22Show fewer
- 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;
- platelets <50x109 cells/L;
- serum potassium <3.0 mmol/L;
- aspartate aminotransferase (AST) ≥3.0 x ULN;
- alanine aminotransferase (ALT) ≥3.0 x ULN;
- Total white cell count <1.5 cells/L
- For participants undergoing PET/CT, the following are excluded:
- Participants with diabetes (Type 1 or 2) with point of care HbA1c above 6.5, or random glucose over 11.1 mmol/L.
Trial locations and contacts
1 site in 1 country.
South Africa1 site
TASK Clinical Research Centre
Cape Town, Western Cape, 7530
About this study
Official title: A Phase 2 Trial to Evaluate the Early Bactericidal Activity, Safety and Tolerability of Sanfetrinem Cilexetil Administered Orally to Adults With Newly Diagnosed, Smear-Positive, Rifampicin-Susceptible Pulmonary Tuberculosis
To evaluate the 2-week bactericidal activity, pharmacokinetics, safety and tolerability of sanfetrinem cilexetil in participants with rifampicin-susceptible pulmonary tuberculosis.
Read the detailed description
A single-centre, open-label, clinical trial in two stages. Stage 1 will recruit 20 participants followed by a recruitment pause and an interim analysis to determine if sanfetrinem cilexetil has early bactericidal activity (EBA). Should EBA be demonstrated, stage 2 will focus on optimising sanfetrinem cilexetil.
All treatments will be administered orally (PO) on days 1-14. The treatments are:
Stage 1:
- Sanfetrinem cilexetil 1.6 g PO 12-hourly
- Rifampicin 35 mg/kg PO once daily (OD)*
An interim analysis is planned after stage 1 to review the pharmacokinetics (PK), safety, tolerability and EBA of sanfetrinem cilexetil. Results of stage 1 will determine whether stage 2 should proceed and if any modifications in dose, duration or combinations are required for Stage 2. If deemed possible, a PK-EBA model will be derived using only stage 1 from which clinical trial simulations will be conducted to inform the design of stage 2. If EBA is not demonstrated, the study will be stopped after stage 1.
Stage 2:
- Rifampicin 35 mg/kg po OD*
- Sanfetrinem cilexetil 2.4 g PO OD
Five of the rifampicin 35 mg/kg arm participants will be recruited in stage 1 and the remainder in stage 2.
Participants on rifampicin will serve as control for the EBA quantitative mycobacteriology.
The study will not be blinded but the mycobacteriology laboratory staff performing the endpoint assays will remain blinded until analysis of the EBA results.
- Conditions
- Tuberculosis, Pulmonary
- Being tested
- Sanfetrinem Cilexetil, Rifampicin
- Keywords
- tuberculosis, early bactericidal activity, bedaquiline, delamanid
- Medical subject headings
- Tuberculosis, Pulmonary, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sanfetrinem CilexetilDrug
Also called Compound number GV118819
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
RifampicinDrug
Also called Rifadin
Rifampicin will be administered at a dose of 35 mg/kg once daily for 14 days with or without sanfetrinem cilexetil.
| Study group | Role | What they receive |
|---|---|---|
| Sanfetrinem cilexetil 1.6 gram 12 hourly | Experimental | Sanfetrinem cilexetil 1.6g will be given orally 12 hourly for 14 consecutive days. Receives: Drug: Sanfetrinem Cilexetil |
| Rifampicin 35 mg/kg once daily | Experimental | Rifampicin 35 mg/kg will be given orally once daily for 14 consecutive days. Receives: Drug: Rifampicin |
| Sanfetrinem cilexetil 2.4 gram once daily | Experimental | Sanfetrinem cilexetil 2.4 g will be given orally daily for 14 consecutive days. Receives: Drug: Sanfetrinem Cilexetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
EBA will be determined, per treatment arm, by the rate of change in time to culture positivity (TTP) over the treatment period day 0 to day 14, and described using linear, bi-linear or non-linear regression of TTD over time and relation to drug exposure
Measured: 14 days
Number of patients with abnormal safety and tolerability findings following the study regimens, administered for 14 days
The pooled incidence of the following events will be summarized by treatment group for further analysis:
Incidence of treatment-emergent adverse events (TEAEs); Incidence of TEAEs by Severity; Incidence of drug related TEAEs; Incidence of Serious TEAEs; Incidence of TEAEs leading to early withdrawal; Incidence of TEAEs leading to death Incidence of treatment-emergent adverse events (TEAEs); Incidence of TEAEs by Severity; Incidence of drug related TEAEs; Incidence of Serious TEAEs; Incidence of TEAEs leading to early withdrawal; Incidence of TEAEs leading to death
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2022
- Study start21 Apr 2022
- Primary completion19 Aug 2024
- Study completion19 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Tuberculosis, PulmonaryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- TASK Applied Science
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline, European and Developing Countries Clinical Trials Partnership (EDCTP)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05388448
- Sponsor's protocol ID
- TASK-009-SANF
- Status last verified
- Feb 2025
- First submitted
- 25 Jan 2022
- Last updated
- 21 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40020440Ramon-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.
PubMed 39803560
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Trial to Evaluate the Early Bactericidal Activity, Safety and Tolerability of Sanfetrinem Cilexetil Administered Orally to Adults With Newly Diagnosed, Smear-Positive, Rifampicin-Susceptible Pulmonary Tuberculosis
- ClinicalTrials.gov ID
- NCT05388448
- Acronym / sponsor ID
- TASK-009-SANF
- Conditions
- Tuberculosis, Pulmonary
- Keywords
- tuberculosis, early bactericidal activity, bedaquiline, delamanid
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- TASK Applied ScienceUniversity, hospital or other
- Collaborators
- GlaxoSmithKline, European and Developing Countries Clinical Trials Partnership (EDCTP)
- Study start
- 21 Apr 2022 (actual)
- Primary completion
- 19 Aug 2024 (actual)
- Study completion
- 19 Aug 2024 (actual)
- First posted
- 24 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the 2-week bactericidal activity, pharmacokinetics, safety and tolerability of sanfetrinem cilexetil in participants with rifampicin-susceptible pulmonary tuberculosis.
Detailed description
A single-centre, open-label, clinical trial in two stages. Stage 1 will recruit 20 participants followed by a recruitment pause and an interim analysis to determine if sanfetrinem cilexetil has early bactericidal activity (EBA). Should EBA be demonstrated, stage 2 will focus on optimising sanfetrinem cilexetil.
All treatments will be administered orally (PO) on days 1-14. The treatments are:
Stage 1:
- Sanfetrinem cilexetil 1.6 g PO 12-hourly
- Rifampicin 35 mg/kg PO once daily (OD)*
An interim analysis is planned after stage 1 to review the pharmacokinetics (PK), safety, tolerability and EBA of sanfetrinem cilexetil. Results of stage 1 will determine whether stage 2 should proceed and if any modifications in dose, duration or combinations are required for Stage 2. If deemed possible, a PK-EBA model will be derived using only stage 1 from which clinical trial simulations will be conducted to inform the design of stage 2. If EBA is not demonstrated, the study will be stopped after stage 1.
Stage 2:
- Rifampicin 35 mg/kg po OD*
- Sanfetrinem cilexetil 2.4 g PO OD
Five of the rifampicin 35 mg/kg arm participants will be recruited in stage 1 and the remainder in stage 2.
Participants on rifampicin will serve as control for the EBA quantitative mycobacteriology.
The study will not be blinded but the mycobacteriology laboratory staff performing the endpoint assays will remain blinded until analysis of the EBA results.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Sanfetrinem cilexetil 1.6 gram 12 hourly | Experimental | Drug: Sanfetrinem CilexetilSanfetrinem cilexetil 1.6g will be given orally 12 hourly for 14 consecutive days. |
| Rifampicin 35 mg/kg once daily | Experimental | Drug: RifampicinRifampicin 35 mg/kg will be given orally once daily for 14 consecutive days. |
| Sanfetrinem cilexetil 2.4 gram once daily | Experimental | Drug: Sanfetrinem CilexetilSanfetrinem cilexetil 2.4 g will be given orally daily for 14 consecutive days. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Participants are required to meet all of the following criteria in order to be randomized.
- 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
Key exclusion criteria (22 listed)
- Participants will be excluded from participation if they fulfil any of the following criteria.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sanfetrinem CilexetilAlso: Compound number GV118819Sanfetrinem 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 | Drug | Sanfetrinem cilexetil 1.6 gram 12 hourly, Sanfetrinem cilexetil 2.4 gram once daily |
| RifampicinAlso: RifadinRifampicin will be administered at a dose of 35 mg/kg once daily for 14 days with or without sanfetrinem cilexetil. | Drug | Rifampicin 35 mg/kg once daily |
Primary outcome
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)
Time frame: 14 days
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.
2 secondary outcomes
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
Time frame: 14 days
Number of patients with abnormal safety and tolerability findings following the study regimens, administered for 14 days
Time frame: 14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2025.
- Derived from this study: PubMed 40020440Ramon-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.
- Derived from this study: PubMed 39803560Ramon-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.
- TASK Homepage - clinical research institute and social enterpriseLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Tuberculosis, Pulmonary
RecruitingPhase 4
Short-term Antibiotic Therapy in Mycobacterium Avium Complex Pulmonary Disease
Mycobacterium Avium Complex Pulmonary Disease
Active, not recruitingObservational study
Mycobacterial and Opportunistic Infections in HIV-Negative Thai and Taiwanese Patients Associated With Autoantibodies to Interferon-gamma
Nontuberculous Mycobacteria, Mycobacterium Tuberculosis
RecruitingPhase 2
BRIGHT-Child TB: Short-Course Treatment for Non-Severe Pulmonary Tuberculosis in Children
Tuberculosis
RecruitingPhase 3
A Study of Quabodepistat-containing Regimens for the Treatment of Drug-resistant Pulmonary Tuberculosis
Rifampicin-Resistant Pulmonary Tuberculosis, Multidrug-Resistant Pulmonary Tuberculosis
Recruiting
Channa Striata and Curcuma Domestica Supplementation in Patients With Active Pulmonary Tuberculosis
Pulmonary Tuberculosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sanfetrinem Cilexetil and Rifampicin in people with Tuberculosis, Pulmonary, run by TASK Applied Science at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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) (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05388448, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2025.