Study of Cysteamine-pantetheine Disulfide (TTI-0102) in Mild to Moderate COVID-19
Primary Purpose
COVID-19, COVID-19 Acute Respiratory Distress Syndrome
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
TTI-0102
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19
Eligibility Criteria
Inclusion Criteria:
- Is between 18 and 80 years of age.
- Is within 72 hours from onset of symptoms consistent with COVID-19 at time of study screening.
- Has at least 2 of the following: fever (oral temperature ≥38°C), cough, shortness of breath, chest x-ray changes consistent with COVID-19 at time of screening.
- Has a laboratory-confirmed SARS-CoV-2 infection as determined by FDA-approved rapid diagnostic (e.g., PCR) assay.
- Has a score of ≤ 2 on the 8-category National Institute of Allergy and Infectious Diseases (NIAID) ordinal rating scale at time of screening. [Protocol Appendix 22.2]
- Agrees to the collection of blood and urine samples, nasopharyngeal (NP) swabs, and non-invasive oxygen monitoring (via pulse oximeter) as required by study protocol.
- Patient or their legally authorized representative is willing and able to provide written informed consent prior to performing study procedures.
- Understands and agrees to comply with planned study procedures.
- Women of childbearing potential must agree to either abstinence or use of at least one primary form of contraception not including hormonal contraception from the time of screening through Day 29 following randomization. All subjects of childbearing potential, including males with partners of childbearing potential, must use highly effective methods of birth control defined as those, alone or in combination, that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly [Protocol Appendix 22.3]. Abstinence is NOT an acceptable method of contraception UNLESS it is the subject's normal practice
Exclusion Criteria:
- Is currently hospitalized.
- Prior history of, or considered to be at risk for, agranulocytosis, nephropathy, liver disease or interstitial pneumonia.
- Current or historic positive human immunodeficiency virus (HIV) test.
- Presence of organ transplant.
- Receipt of cancer chemotherapy or immunomodulatory drugs including but not limited to biologics such as anti-CD20, anti-TNF, anti-IL6; alkylating agents (e.g., cyclophosphamide), antimetabolites (e.g., azathioprine), or chronic corticosteroid use equivalent to prednisone >10 gm/day, during the 2 months prior to screening.
- Confirmed positive for influenza at screening.
- Confirmed positive for respiratory syncytial virus (RSV) at screening.
- Pregnant or breastfeeding.
- Current use of, or known allergy to cysteamine, bucillamine or penicillamine (e.g., for Wilson's disease, rheumatoid arthritis).
- Current participation in any other clinical trial of an experimental treatment for any indication including COVID-19.
- Receipt of any experimental treatment for COVID-19 (herbal, homeopathic, over the counter, off-label, compassionate use, or clinical trial related) within the 30 days prior to screening.
- Receipt of any medication for treatment or prevention of COVID-19 being used pursuant to an Emergency Use Authorization (e.g., vaccine) prior to or during study participation
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
TTI-0102
Placebo
Arm Description
Cysteamine-pantetheine disulfide (TTI-0102) is supplied in a vial as a powder to be dissolved in water and administered orally.
Placebo is supplied in a vial as a powder to be dissolved in water and administered orally.
Outcomes
Primary Outcome Measures
Primary Endpoint
Frequency of hospitalization or death
Secondary Outcome Measures
Secondary: Safety
Frequency of adverse events
Secondary: Efficacy
Change of COVID-19 symptoms (self-assessment) score from Baseline, as measured at Day 14 and Day 28.
Full Information
NCT ID
NCT05212662
First Posted
January 26, 2022
Last Updated
May 1, 2023
Sponsor
Thiogenesis Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05212662
Brief Title
Study of Cysteamine-pantetheine Disulfide (TTI-0102) in Mild to Moderate COVID-19
Official Title
A Multi-center, Randomized, Double-blind, Placebo-controlled, Study to Assess the Safety, Tolerability, Pharmacodynamics (PD) and Efficacy of TTI-0102 for the Treatment of Patients With Mild to Moderate COVID-19
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
June 2024 (Anticipated)
Primary Completion Date
June 2025 (Anticipated)
Study Completion Date
September 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Thiogenesis Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is multi-center, randomized, double-blind, placebo-controlled study to assess the safety, tolerability, pharmacodynamics (PD) and efficacy of TTI-0102 for the treatment of patients with mild to moderate COVID-19. This is a phase 2 study of cysteamine-pantetheine disulfide (TTI-0102), an antiviral, anti-infectious, antioxidant and anti-CRS (cytokine release syndrome) investigational drug. Subjects will be randomized 2:1 to receive TTI-0102 or placebo daily for up to 14 days. Up to 5 centers in the US and Canada will conduct this study. 60 patients will be enrolled.
Detailed Description
All patients with confirmed COVID-19 will be managed within an outpatient continuum of care management program that includes self-assessment tools; initial telephone triage; coordinated outreach and management approach based upon individual patient risk, severity of symptoms, and time course of disease; clinician telehealth (telephone call or video platform-based) visits (initial evaluation and follow-up visits); COVID-19 testing; a separate outpatient respiratory clinic or dedicated space within an ambulatory clinic appropriated for the care of patients with COVID-19 and other respiratory problems; strategies to reduce the risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by staff and other patients will be employed.
Screening Period - Remote Patients will undergo screening to determine study eligibility, for a period of not more than 7 days. It is not required that patients come to study investigator clinic for screening assessments, but SARS-CoV-2 PCR test results, medical history and vital signs used to verify study eligibility must be collected from the non-investigator facility that performed them, reviewed prior to Day 1, placed in the subjects' source documentation and transcribed to the CRF. The Ethics Committee or Institutional Review Board must approve the informed consent template and the remote consent process and documentation to be utilized for the trial.
Treatment Period (Days 1-14)
Day 1 Clinic Visit: Eligible subjects will be enrolled into the study, i.e. randomization will take place, they will receive their first dose of study drug (TTI-0102 or placebo) in clinic, and they will be dispensed enough to continue treatment at home for up to 14 days. Baseline assessments will be performed according to Appendix 22.1 Schedule of Assessments.
Day 8 - Remote Visit: Subjects will be contacted to assess their tolerance to study drug. Subjects unable to tolerate the 5.5 gram daily dose (QD) will be instructed to split the dose into two 2.75 gram half-doses taken in the morning and the evening (BID).
Day 14 - Clinic Visit: Subjects will return to clinic for end-of-treatment assessments specified in Appendix 22.1 Schedule of Assessments.
Subjects will continue daily study drug treatment as outpatients, under home quarantine as per local Public Health guidelines. Subjects will also receive continued standard of care therapy per study site written policies or guidelines. Study drug treatmetn should continue for 14 days, or earlier as medically appropriate (e.g., deterioration of clinical status and alternative therapy required). If the patient requires hospitalization during the study period, study drug treatment will be discontinued.
The following safety assessments will be performed at timepoints specified in the Appendix 22.1 Schedule of Assessments. In addition to unsolicited, spontaneous adverse events which are reported or observed, patients will be interviewed for additional cysteamine-associated adverse events using a protocol-specific checklist [Appendix 22.8]. Subjects will also be asked to complete the Gastrointestinal Symptom Rating Scale (GSRS) [Appendix 22.7] and a COVID-19 symptoms questionnaire [Appendix 22.6].
If a patient is required to show up in an outpatient clinic, physical examinations, electrocardiograms (ECGs), vital signs, and clinical laboratory evaluations (chemistry, hematology, urinalysis) will be performed. A standardized toxicity grading scale will be used to grade the severity of adverse events, National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) [Appendix 22.9].
Study Termination: Day 28 or upon Early Withdrawal - Remote Visit A remote (telephone or video) Study Termination Visit will take place on Day 28 for patients who completed treatment or, for patients who withdraw early, 2 weeks (14 days) after the last study drug dose.
Follow-up Period - Remote Visits Follow-up telephone contact #1 will be performed on Day 42 or 28 days/4 weeks after last study drug dose. Follow-up telephone contact #2 will take place on Day 70, or 56 days/7 weeks after last study drug dose.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, COVID-19 Acute Respiratory Distress Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
TTI-0102
Arm Type
Experimental
Arm Description
Cysteamine-pantetheine disulfide (TTI-0102) is supplied in a vial as a powder to be dissolved in water and administered orally.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo is supplied in a vial as a powder to be dissolved in water and administered orally.
Intervention Type
Drug
Intervention Name(s)
TTI-0102
Other Intervention Name(s)
cysteamine-pantetheine disulfide
Intervention Description
The study treatment is a precursor to cysteamine, TTI-0102 (cysteamine-pantetheine disulfide). Each molecule of TTI-0102, after reduction and metabolism in the digestive tract, allows the absorption of 2 molecules of cysteamine and one molecule of pantothenic acid (Vit B5). Each dose of TTI-0102 comes in a vial as a powder to dissolve in water and absorb orally. Each vial contains 5.5g of TTI-0102, corresponding to the equivalent of 2.4g of cysteamine base. This single dose is less than the maximum daily dose authorized with other formulations of cysteamine (Cystagon or Procysbi, 1.95 g/m2/day) for patients over 1.25 m2 or 40 kg (88 lbs).
This dose of 5.5 g is justified by the need to maintain a thiol/disulfide ratio in favor of cysteamine over 24 h. It has been tested in healthy volunteers and has no side effects due to the specific pharmacokinetics of cysteamine after administration of TTI-0102.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo comparator supplied in vials identical to the active intervention, TTI-0102
Primary Outcome Measure Information:
Title
Primary Endpoint
Description
Frequency of hospitalization or death
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Secondary: Safety
Description
Frequency of adverse events
Time Frame
28 days
Title
Secondary: Efficacy
Description
Change of COVID-19 symptoms (self-assessment) score from Baseline, as measured at Day 14 and Day 28.
Time Frame
28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Is between 18 and 80 years of age.
Is within 72 hours from onset of symptoms consistent with COVID-19 at time of study screening.
Has at least 2 of the following: fever (oral temperature ≥38°C), cough, shortness of breath, chest x-ray changes consistent with COVID-19 at time of screening.
Has a laboratory-confirmed SARS-CoV-2 infection as determined by FDA-approved rapid diagnostic (e.g., PCR) assay.
Has a score of ≤ 2 on the 8-category National Institute of Allergy and Infectious Diseases (NIAID) ordinal rating scale at time of screening. [Protocol Appendix 22.2]
Agrees to the collection of blood and urine samples, nasopharyngeal (NP) swabs, and non-invasive oxygen monitoring (via pulse oximeter) as required by study protocol.
Patient or their legally authorized representative is willing and able to provide written informed consent prior to performing study procedures.
Understands and agrees to comply with planned study procedures.
Women of childbearing potential must agree to either abstinence or use of at least one primary form of contraception not including hormonal contraception from the time of screening through Day 29 following randomization. All subjects of childbearing potential, including males with partners of childbearing potential, must use highly effective methods of birth control defined as those, alone or in combination, that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly [Protocol Appendix 22.3]. Abstinence is NOT an acceptable method of contraception UNLESS it is the subject's normal practice
Exclusion Criteria:
Is currently hospitalized.
Prior history of, or considered to be at risk for, agranulocytosis, nephropathy, liver disease or interstitial pneumonia.
Current or historic positive human immunodeficiency virus (HIV) test.
Presence of organ transplant.
Receipt of cancer chemotherapy or immunomodulatory drugs including but not limited to biologics such as anti-CD20, anti-TNF, anti-IL6; alkylating agents (e.g., cyclophosphamide), antimetabolites (e.g., azathioprine), or chronic corticosteroid use equivalent to prednisone >10 gm/day, during the 2 months prior to screening.
Confirmed positive for influenza at screening.
Confirmed positive for respiratory syncytial virus (RSV) at screening.
Pregnant or breastfeeding.
Current use of, or known allergy to cysteamine, bucillamine or penicillamine (e.g., for Wilson's disease, rheumatoid arthritis).
Current participation in any other clinical trial of an experimental treatment for any indication including COVID-19.
Receipt of any experimental treatment for COVID-19 (herbal, homeopathic, over the counter, off-label, compassionate use, or clinical trial related) within the 30 days prior to screening.
Receipt of any medication for treatment or prevention of COVID-19 being used pursuant to an Emergency Use Authorization (e.g., vaccine) prior to or during study participation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
COVID-19 Clinical Trial Recruitment
Phone
+1 (858) 500-6621
Email
mbagger@thiogenesis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Patrice P Rioux, MD, PhD
Phone
+1 (408) 677-0682
Email
prioux@thiogenesis.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrice P Rioux, MD, PhD
Organizational Affiliation
Sponsor: Thiogenesis Therapeutics, Inc.
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of Cysteamine-pantetheine Disulfide (TTI-0102) in Mild to Moderate COVID-19
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