Reducing Hypoxia in Patients With Coronavirus Disease (COVID-19) Using Topotecan With Standard of Care

NCT05083000 | Unknown Phase 1 DMC

• 1 other identifier: TOTORO1
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

COVID-19 Respiratory Infection

Keywords

Topotecan; hypoxia

Outcome Measures

Primary Outcomes (1)

• 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

  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

  1 week from administration of Topotecan

• Rate of treatment related CTCAE grade 3/4 haematological toxicity

  Up to Day 10 from Topotecan administration

• Number of participant with Serious Adverse Events

  Within 14 days from Topotecan administration

• Proportion of patients requiring ICU care

  28 days from Topotecan administration

• Proportion of patients requiring mechanical ventilation

  28 days from Topotecan administration

Study Arms (1)

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.

Drug: Topotecan

Interventions

Topotecan DRUG

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.

Also known as: Topotecan hydrochloride

Topotecan

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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:
• i. 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• Christian Medical College, Vellore, India: collaborator

Study Sites (1)

Christian Medical College

Vellore, Tamil Nadu, 632004, India

RECRUITING

MeSH Terms

Conditions

Hypoxia

Interventions

Topotecan

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Anand JEYASEKHARAN

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anand JEYASEKHARAN

CONTACT

+65 6779 5555; anand_jeyasekharan@nuhs.edu.sg

Anand JEYASEKHARAN

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: October 11, 2021
• First Posted: October 19, 2021
• Study Start: August 16, 2021
• Primary Completion: December 31, 2021
• Study Completion: March 31, 2022
• Last Updated: November 4, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)