COVID-19 Respiratory InfectionPhase 1NCT05083000
Reducing Hypoxia in Patients With Coronavirus Disease (COVID-19) Using Topotecan With Standard of Care
A Phase 1 study testing Topotecan in people with COVID-19 Respiratory Infection, run by National University Hospital, Singapore at 1 site in India.
Trial summary
The primary objective of the phase 1 trial is to identify a dose of topotecan that will be safe to take forward into a Phase 2 trial, with no unexpected toxicities or drug-drug interactions with standard therapy for COVID-19. Read more about this study
- Who is it for?
- Ages 21 to 99 years
- Conditions the study is for
- COVID-19 Respiratory Infection
- What is being tested?
- Topotecan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteIndia
- Study dates
- 16 Aug 2021to 31 Mar 2022
- Phase
- Phase 1
- 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 21 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by at least 1 positive Polymerase Chain Reaction (PCR) test
- Moderate COVID as evidenced by Oxygen saturation <93% on room air (or <88% if prior CLD)
- Admission to emergency department for monitoring and/or supportive care:
- The following biochemical markers:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. Platelets ≥ 100 x 109/L, Haemoglobin ≥ 9x 109/L.
- Bilirubin < 1.5 times upper limit of normal (ULN). Alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST) < 2.5 times ULN.
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- Calculated creatinine clearance of ≥ 30ml/min calculated using the formula of Cockcroft and Gault: (140-age) x mass (kg)/)72x creatinine mg/dl); multiple by 0.85 if female.
- Laboratory features of cytokine release, as defined by any 1 of the following:
- C-reactive protein (CRP)> 75mg/L ii. Lactate Dehydrogenase (LDH) > ULN iii. D-dimer > 1.0 mg/L iv. Ferritin > 500ng/ml v. Elevated Interleukin-6 levels
Who cannot join
- Patients requiring mechanical ventilation
- Any immunosuppressive medication including chemotherapy(excluding steroids) administered concurrently or within last 14 days.
- Patients with uncontrolled diabetes mellitus (HbA1C within 1 month >8)
- Pregnancy or Breastfeeding.
- Known allergy to Topotecan. Unconjugated hyperbilirubinemia on a fasting Liver Function Test (LFT), which can indicate Gilberts Syndrome.
- Suspected active bacterial, fungal, or other infection in addition to COVID-19.
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- Any condition that would, in the opinion of the Investigator, increase the risk of the participant
- by participating in the study.
- Inability to provide consent.
- Unable to comply with study procedures.
Trial locations and contacts
1 site in 1 country.
Anand JEYASEKHARAN contact
India1 site, 1 recruiting
- Recruiting
Christian Medical College
Vellore, Tamil Nadu, 632004
Ajoy Oommen John, +91 7639195315, ajoyoommenjohn@gmail.com
Ashish Singh, todrashish@gmail.com
About this study
Official title: Phase I Dose-escalation Study of Topotecan in Moderate-severe COVID-19 Patients
The primary objective of the phase 1 trial is to identify a dose of topotecan that will be safe to take forward into a Phase 2 trial, with no unexpected toxicities or drug-drug interactions with standard therapy for COVID-19. The investigators hypothesise that a single dose of low-dose Topotecan will blunt the expression of inflammatory genes in patients with moderate COVID-19, without cytotoxic side effects.
Read the detailed description
4 fixed dosing levels (0.25 -0.5mg) of Topotecan will be evaluated in this trial, using sub-cytotoxic doses of Topotecan which are well below typical chemotherapy levels and shown not to cause myelosuppression in previously tested populations. The dose escalation will be in a standard 3+3 dose escalation design with 0.25 mg increments of Topotecan. The study aims to establish the recommended phase 2 dose (RP2D) of Topotecan in hypoxic patients with moderate to severe COVID-19.The RP2D is defined as the maximum safe dose at which 3 or more patients are found to have clinically relevant concentrations of Topotecan in the blood stream, without reaching anti-cancer concentrations in plasma (defined as Area under the curve (AUC)>150000) and without causing Grade 2/3/4 neutropenia (CTCAE5).
- Conditions
- COVID-19 Respiratory Infection
- Being tested
- Topotecan
- Keywords
- Topotecan, hypoxia
- Medical subject headings
- Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TopotecanDrug
Also called Topotecan hydrochloride
Topotecan hydrochloride is a semi-synthetic derivative of camptothecin and is an anti-tumor drug with topoisomerase I-inhibitor activity. It is a well-established chemotherapeutic agent used for cancer treatment.
| Study group | Role | What they receive |
|---|---|---|
| Topotecan | Experimental | Subject will receive Topotecan as a single dose or 2 consecutive doses given via intravenous (IV). The starting dose level of Topotecan is 0.25mg. Subsequent dose levels will be 2 doses of 0.25mg, a single dose of 0.5mg and then 2 doses of 0.5mg.
Standard of care treatments for COVID-19 will be given together if available as per the following protocol:
1. IV Dexamethasone 6mg once daily for at least 5 days and not more than 10 days.
2. IV Remdesivir 200mg loading dose on day 1 followed by 100mg once daily for 4 days. Receives: Drug: Topotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal tolerable dose of Topotecan
To determine a maximal dose of Topotecan, at which less than 1 out of 3 patients exhibit anti-cancer concentrations in plasma, or have G2/3/4 neutropenia
Measured: 24 hours and 14 days from the time of Topotecan administration
Secondary outcomes (8)
Rate of reduction in the duration of supplemental oxygen requirement in participants
Determine effect of Topotecan on duration of additional oxygen requirements
Measured: 1 week from administration of Topotecan
Rate of treatment related CTCAE grade 3/4 haematological toxicity
Dose limiting toxicities will be graded using CTCAE version 5.0.
Measured: Up to Day 10 from Topotecan administration
Number of participant with Serious Adverse Events
Serious Adverse Events experience by subject after Topotecan administration (related and unrelated).
Measured: Within 14 days from Topotecan administration
Proportion of patients requiring ICU care
Number of patients requiring intubation/inotropic/vasopressor support
Measured: 28 days from Topotecan administration
Proportion of patients requiring mechanical ventilation
Number of patients requiring mechanical ventilation
Measured: 28 days from Topotecan administration
Time to discharge
Time to hospital discharge in days
Measured: 28 days from Topotecan administration
Proportion of patients with secondary infections
Number of patients with secondary infections
Measured: 28 days from Topotecan administration
Proportion of patients who died after enrolment into trial
Death from related and unrelated causes
Measured: 28 days from Topotecan administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2021
- Study start16 Aug 2021
- Primary completion31 Dec 2021 (estimated)
- Study completion31 Mar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19 Respiratory InfectionStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- The dose escalation will be in a standard 3+3 dose escalation design with 0.25mg increments of Topotecan; it will begin with a single dose 0.25mg for 3 patients-expanded to another 3 if no toxicities are seen. Subsequent dose levels will be 2 doses of 0.25mg, a single dose of 0.5mg and then 2 doses of 0.5mg (maximum of 24 patients).
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- Christian Medical College, Vellore, India
- Responsible party
- Sponsor
- Investigators
- Anand JEYASEKHARAN, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05083000
- Sponsor's protocol ID
- TOTORO1
- Status last verified
- Sep 2021
- First submitted
- 11 Oct 2021
- Last updated
- 4 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose-escalation Study of Topotecan in Moderate-severe COVID-19 Patients
- ClinicalTrials.gov ID
- NCT05083000
- Acronym / sponsor ID
- TOTORO1
- Conditions
- COVID-19 Respiratory Infection
- Keywords
- Topotecan, hypoxia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Collaborators
- Christian Medical College, Vellore, India
- Study start
- 16 Aug 2021 (actual)
- Primary completion
- 31 Dec 2021 (estimated)
- Study completion
- 31 Mar 2022 (estimated)
- First posted
- 19 Oct 2021 (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.
The primary objective of the phase 1 trial is to identify a dose of topotecan that will be safe to take forward into a Phase 2 trial, with no unexpected toxicities or drug-drug interactions with standard therapy for COVID-19. The investigators hypothesise that a single dose of low-dose Topotecan will blunt the expression of inflammatory genes in patients with moderate COVID-19, without cytotoxic side effects.
Detailed description
4 fixed dosing levels (0.25 -0.5mg) of Topotecan will be evaluated in this trial, using sub-cytotoxic doses of Topotecan which are well below typical chemotherapy levels and shown not to cause myelosuppression in previously tested populations. The dose escalation will be in a standard 3+3 dose escalation design with 0.25 mg increments of Topotecan. The study aims to establish the recommended phase 2 dose (RP2D) of Topotecan in hypoxic patients with moderate to severe COVID-19.The RP2D is defined as the maximum safe dose at which 3 or more patients are found to have clinically relevant concentrations of Topotecan in the blood stream, without reaching anti-cancer concentrations in plasma (defined as Area under the curve (AUC)>150000) and without causing Grade 2/3/4 neutropenia (CTCAE5).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The dose escalation will be in a standard 3+3 dose escalation design with 0.25mg increments of Topotecan; it will begin with a single dose 0.25mg for 3 patients-expanded to another 3 if no toxicities are seen. Subsequent dose levels will be 2 doses of 0.25mg, a single dose of 0.5mg and then 2 doses of 0.5mg (maximum of 24 patients).
| Arm | Type | Receives |
|---|---|---|
| Topotecan | Experimental | Drug: TopotecanSubject will receive Topotecan as a single dose or 2 consecutive doses given via intravenous (IV). The starting dose level of Topotecan is 0.25mg. Subsequent dose levels will be 2 doses of 0.25mg, a single dose of 0.5mg and then 2 doses of 0.5mg. Standard of care treatments for COVID-19 will be given together if available as per the following protocol: 1. IV Dexamethasone 6mg once daily for at least 5 days and not more than 10 days. 2. IV Remdesivir 200mg loading dose on day 1 followed by 100mg once daily for 4 days. |
Who may qualify
- Ages
- 21 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by at least 1 positive Polymerase Chain Reaction (PCR) test
- Moderate COVID as evidenced by Oxygen saturation <93% on room air (or <88% if prior CLD)
- Admission to emergency department for monitoring and/or supportive care:
- The following biochemical markers:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. Platelets ≥ 100 x 109/L, Haemoglobin ≥ 9x 109/L.
Key exclusion criteria (10 listed)
- Patients requiring mechanical ventilation
- Any immunosuppressive medication including chemotherapy(excluding steroids) administered concurrently or within last 14 days.
- Patients with uncontrolled diabetes mellitus (HbA1C within 1 month >8)
- Pregnancy or Breastfeeding.
- Known allergy to Topotecan. Unconjugated hyperbilirubinemia on a fasting Liver Function Test (LFT), which can indicate Gilberts Syndrome.
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 |
|---|---|---|
| TopotecanAlso: Topotecan hydrochlorideTopotecan hydrochloride is a semi-synthetic derivative of camptothecin and is an anti-tumor drug with topoisomerase I-inhibitor activity. It is a well-established chemotherapeutic agent used for cancer treatment. | Drug | Topotecan |
Primary outcome
Maximal tolerable dose of Topotecan
Time frame: 24 hours and 14 days from the time of Topotecan administration
To determine a maximal dose of Topotecan, at which less than 1 out of 3 patients exhibit anti-cancer concentrations in plasma, or have G2/3/4 neutropenia
8 secondary outcomes
Rate of reduction in the duration of supplemental oxygen requirement in participants
Time frame: 1 week from administration of Topotecan
Rate of treatment related CTCAE grade 3/4 haematological toxicity
Time frame: Up to Day 10 from Topotecan administration
Number of participant with Serious Adverse Events
Time frame: Within 14 days from Topotecan administration
Proportion of patients requiring ICU care
Time frame: 28 days from Topotecan administration
Proportion of patients requiring mechanical ventilation
Time frame: 28 days from Topotecan administration
Time to discharge
Time frame: 28 days from Topotecan administration
Proportion of patients with secondary infections
Time frame: 28 days from Topotecan administration
Proportion of patients who died after enrolment into trial
Time frame: 28 days from Topotecan administration
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2021.
- Individual participant dataSharing planned: No
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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.
Anand JEYASEKHARAN contact
Anand JEYASEKHARAN principal investigator
National University Hospital, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Topotecan in people with COVID-19 Respiratory Infection, run by National University Hospital, Singapore at 1 site in India.
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 9 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 4 Nov 2021. 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 India. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Anand JEYASEKHARAN (+65 6779 5555, anand_jeyasekharan@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal tolerable dose of Topotecan (time frame: 24 hours and 14 days from the time of Topotecan administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Nov 2021; AzTrials last refreshed its copy on 6 Nov 2026.