Cysteamine in association with standard therapy for the treatment of hospitalized patients with COVID-19 pneumonia: phase 2 study on safety of a new antiviral and direct therapy on the host

Overview

Sponsor-declared trial summary

Key facts

Sponsor

National Institute For Infectious Diseases Lazzaro Spallanzani

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Virus Diseases [C02]

Decision date (initial)

2024-10-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-516800-40-00

EudraCT number

2022-001819-12

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Safety of cysteamine in hospitalized patients with COVID-19 pneumonia not requiring high oxygen flows, whether or not previously vaccinated with anti-COVID-19 vaccines.

Secondary objectives 3

1. Evaluation of therapeutic adherence and tolerability of the orally administered drug cysteamine in two different dosing regimens, 1050 mg/day and 1950 mg/day. Correlation of any adverse events with cysteamine blood levels.
2. Description of the pharmacokinetic curve at day 7±1 (blood draws at 0, 1, 2 and 3 hours after drug administration).
3. Immunological characterization of cysteamine activity

Conditions and MedDRA coding

Infectious diseases of respiratory system (COVID-19)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Age ≥18 years
2. Positive nasopharyngeal swab for SARS-CoV-2 (antigenic or molecular test)
3. Onset of COVID-19 symptoms related ≤10 days
4. Clinical signs and symptoms of COVID-19 pneumonia
5. Imaging examination (X-ray/echo/TAC) of the chest compatible with COVID-19 pneumonia not requiring high oxygen flows
6. Low-flow respiratory support with Venturi mask or goggles with a pO2/FiO2 ratio (index derived from the ratio of PaO2 detected by blood gas analysis, to the fraction of oxygen, FiO2 administered) > 200mmHg
7. Body Weight ≥50 kg
8. Ability to provide informed consent
9. Ability to adhere to follow-up visits
10. Infertility condition (postmenopausal, surgically induced infertility e.g., vasectomy with documented azoospermia for men or tubal closure for women) or in potentially fertile subjects, negative urinary pregnancy test (women), and consent to adhere to the following contraception requirements from 2 weeks prior to enrollment to 18 weeks after experimental drug administration (men and women)

Exclusion criteria 17

1. Age <18 years
2. pO2/FiO2 ratio ≤ 200 mmHg
3. Need for oxygen at high flows (CPAP/NIV/VM/ECMO)
4. Use of antiretroviral drugs
5. Hemoglobin concentration less than 10 g/dl
6. Elevation of creatinine kinase at baseline more than three times the upper limit of normal
7. Abnormal laboratory values at baseline (baseline alanine aminotransferase (ALT) concentration more than three times the upper limit of normal, serum creatinine concentration more than twice the upper limit of normal, serum total bilirubin level more than twice the upper limit of normal, platelet count <100,000/mm3, white blood cell (WBC) <2500 (mcL)
8. Pregnancy or breastfeeding
9. Silico-tuberculosis
10. Seropositivity for HIV, HCV, HBV (HBsAg positivity)
11. Liver failure (Child A-C), renal failure (creatinine clearance < 50 ml/min), heart failure (NYHA IV), active stage neoplasms (those who have had cycles of chemotherapy including biologic drugs and/or radiation therapy in the past 6 months), ongoing neurological/psychiatric pathology (e.g., depression, psychotic crisis, suicide attempt)
12. Gastric/duodenal ulcer undergoing treatment
13. Systemic lupus erythematosus (autoimmune disease)
14. Hypersensitivity to cysteamine or penicillin
15. Drug/alcohol abuse
16. Inability to understand and sign informed consent
17. Presence of any physical or psychological condition that, in the opinion of the principal investigator, makes participation in the study not recommended

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Percentage of patients with treatment-related AEs of grade ≥3 within 28 days and 90 days after the start of therapy
2. Percentage of patients with AEs (of any grade and those with serious conditions) of any grade and regardless of causality within 28 days and 90 days after the start of therapy

Secondary endpoints 8

1. Percentage of patients who decide to discontinue therapy before day 10 or discharge
2. Difference between number of tablets taken and expected number of cysteamine tablets
3. Pharmacokinetic curve of cysteamine at day 7±1 (blood draws at 0, 1, 2 and 3 hours after drug administration)
4. Cytokines and blood biomarkers at baseline and days 3, 7±1 (or hospital discharge if before day 10), 28±3.
5. Modulation of gene expression induced by cysteamine therapy at day 7±1 compared with baseline
6. Number of days required for SARS-COV-2 swab negativization.
7. Clinical status expressed by the 11 items of the WHO Clinical Progression Scale at day 7, 10 and 28.
8. Number of days to hospital discharge

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

National Institute For Infectious Diseases Lazzaro Spallanzani

Sponsor organisation

National Institute For Infectious Diseases Lazzaro Spallanzani

Address

Via Portuense 292

City

Rome

Postcode

00149

Country

Italy

Scientific contact point

Organisation

National Institute For Infectious Diseases Lazzaro Spallanzani

Contact name

Emanuele Nicastri

Public contact point

Organisation

National Institute For Infectious Diseases Lazzaro Spallanzani

Contact name

Emanuele Nicastri

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications