The Safety and Efficacy of Pyronaridine-artesunate (Pyramax® or Artecom®)in COVID-19 Patients

NCT04701606 | Unknown Phase 2 DMC

• 1 other identifier: SP-PA-COV-203
• Study Type: interventional
• Target: 402
• Locations: 1 country
• Sites: 4

Brief Summary

This is a multi-center, randomized, Phase 2/3 study to evaluate the safety and efficacy of pyronaridine-artesunate in participants with corona virus disease 2019 (COVID-19). Pyronaridine-artesunate has been approved in Europe, Asia and Africa under brand name of Pyramax® or Artecom® as a treatment for malaria. The study will be conducted in two stages: open-label (Stage 1) and double-blind (Stage 2). Up to approximately 402 participants (20 participants in Stage 1 and 382 participants in Stage 2) are planned to be enrolled in the study and will be randomized to receive either Artecom® or matching placebo at a ratio of 1:1 in Stage 2. The dose of Artecom® will be determined by the participant's body weight, according to previously established guidelines. An independent Drug Safety Monitoring Board (DSMB) will be established to review the safety at regular intervals during the conduct of the trial. The DSMB will be subject to a Charter and will review after 20 participants have been recruited, and thereafter when 191 participants have been recruited. Ad-hoc DSMB meetings may be held at any time during the study if there are any major safety concerns. A final DSMB will be conducted when all participants have been recruited in the trial.

Conditions

Covid19

Keywords

Pyramax; COVID-19; pyronaridine-artesunate; SARS-CoV-2; Artecom

Outcome Measures

Primary Outcomes (1)

• Proportion of participants with clinical improvement as defined by an improvement of categories on the WHO Ordinal Scale of clinical status until Days 28.

  \* WHO Ordinal scale: 0. No clinical or virological evidence of infection 1. No limitation of activities 2. Limitation of activities 3. Hospitalized, no oxygen therapy 4. Oxygen by mask or nasal prongs 5. Non-invasive ventilation or high-flow oxygen 6. Intubation and mechanical ventilation 7. Ventilation + additional organ support - Pressers, Renal replacement therapy (RRT), extracorporeal membrane oxygenation (ECMO) 8. Death

  follows up to 28 days

Secondary Outcomes (12)

• Time to clinical improvement was defined as time from randomization to an improvement of categories on the WHO Ordinal Scale of clinical status.

  follows up to 28 days

• Changes in the WHO Ordinal Scale for Clinical Improvement until Days 28 compared to Baseline.

  follows up to 28 days

• Changes in National Early Warning Score (NEWS) until Days 28 compared to Baseline.

  follows up to 28 days

• Proportion of participants with negative for COVID-19 as determined by real-time RT-PCR test until Days 14.

  follows up to 14 days

• Changes in viral load until Days 14 compared to Baseline.

  follows up to 14 days

Study Arms (2)

Artecom® (pyronaridine-artesunate)

EXPERIMENTAL

Artecom® is treated orally once a day for 3 consecutive days.

Drug: Artecom® (pyronaridine-artesunate)

Placebo

PLACEBO COMPARATOR

Placebo is treated orally once a day for 3 consecutive days.

Drug: Placebo

Interventions

Artecom® (pyronaridine-artesunate) DRUG

\* Participant body weight (Artecom® dose) * ≥ 65kg (Artecom® 4 tablets: Pyronaridine 720mg/ Artesunate 240mg) * ≥ 45kg and \< 65kg (Artecom® 3 tablets: Pyronaridine 540mg/ Artesunate 180mg)

Also known as: Pyramax® (pyronaridine-artesunate)

Artecom® (pyronaridine-artesunate)

Placebo DRUG

\* Participant body weight (Placebo dose) * ≥ 65kg (Placebo 4 tablets) * ≥ 45kg and \< 65kg (Placebo 3 tablets)

Placebo

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female adults age (≥19 years at the time of informed consent)
• Body weight (≥ 45 kg at Screening)
• Participants must be confirmed as having COVID-19 using real-time reverse transcription polymerase chain reaction (RT-PCR) test and specimens collected from upper airway (nasopharyngeal specimen) within 96 hours prior to randomization.
• Females must be non-pregnant and non-lactating, and must use an acceptable, highly effective double contraception from Screening until study completion, including the follow-up period. Males must be surgically sterile (\>30 days since vasectomy with no viable sperm), abstinent, or if engaged in sexual relations with a woman of childbearing potential (WOCBP), the participant and his partner must be surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or using an acceptable, highly effective contraceptive method from Screening until study completion, including the follow-up period.
• Hormonal contraception (with approved oral contraceptives, long-acting implantable hormones, injectable hormones), intra uterine device, condoms , sterilization (vasectomy, tubal occlusion, etc.)

You may not qualify if:

• Participants with clinically significant cardiovascular disease (including arrhythmia, corrected QT interval prolongation \[QTcF\> 470 msec for females, or \>450 msec for males, at Screening\])
• Participants with clinically significant anemia (Hemoglobin \<8.0 g/dL)
• Participants who have hypersensitivity to main ingredients (pyronaridine tetraphosphate, artesunate) and any excipient in the IP
• Participants who have gastrointestinal disease or surgical participant that may affect absorption, distribution, metabolism and excretion of drugs, current active gastritis, gastrointestinal /rectal bleeding, gastric ulcers, pancreatic abnormalities such as pancreatitis, etc. (simple appendectomy or hernia surgery not excluded)
• Participants who have received antiviral drugs for the treatment of COVID-19 infection or other indications within 28 days prior to participation in the study or who have not had sufficient wash-out period of the antiviral drugs
• Participants with severe renal impairment (estimated glomerular filtration rate ≤30 mL/min/1.73 m2)
• Participants with severe hepatic impairment (Alanine aminotransferase or Aspartate aminotransferase ≥5x upper limit of normal) or have symptoms of abdominal pain or vomiting associated with Jaundice or Child-Pugh Stage B or C
• Viral infections other than COVID-19 that requires administration of other antiviral agents (for example but not limited to human immunodeficiency virus, hepatitis B virus, hepatitis C virus)
• Participants requiring mechanical ventilation (e.g. non-invasive ventilation, invasive mechanical ventilation, extracorporeal membrane oxygenation etc.). However, those who can be given oral administration are not exdluded.
• Participants with chronic underlying diseases (such as uncontrolled diabetes, chronic kidney disease, chronic liver disease, chronic lung disease \[including asthma, chronic obstructive pulmonary disease and tuberculosis\], chronic cardiovascular disease, blood cancer, cancer participants with anti-cancer treatment, participants taking immunosuppressants, etc.), participants with high obesity (BMI \> 40), dialysis participants, transplant participants whom are inadequate to participate in clinical trials based on the Investigator's discretion.
• Pregnant or lactating at Screening or planning to become pregnant (self or partner) at any time during the study, including the follow-up period.
• Participants who participated in another clinical trial / medical device clinical trial within 28 days from the date of signing the consent and received drug / operated medical device for clinical trial.
• Prior or ongoing medical conditions, medical history, physical findings, or laboratory abnormality that, in the Investigator's (or delegate's) opinion, could adversely affect the safety of the participant.

Sponsors & Collaborators

• Shin Poong Pharmaceutical Co. Ltd.: lead

Study Sites (4)

De La Salle University Medical Center

Dasmariñas, Gov, D. Mangubat St, 4114 Cavite, Philippines

RECRUITING

The Medical City

Pasig, Ortigas Avenue, Barangay Ugong, Metro Manila, Philippines

NOT YET RECRUITING

Lung Center of the Philippines

Quezon City, Quezon Avenue, Quezon City, 1100 Philippines, Philippines

RECRUITING

Philippine General Hospital

Manila, Taft Ave, Ermita, Manila, 1000 Metro, Philippines

RECRUITING

MeSH Terms

Conditions

COVID-19

Interventions

pyronaridine tetraphosphate, artesunate drug combination

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Belen L Dofitas, MD, PhD

  Philippine General Hospital, University of the Philippines

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Belen L Dofitas, MD, PhD

CONTACT

+63-917-629-4329; belendofitas@gmail.com

Byung Su Kim, MS

CONTACT

+82-31-348-9354; 135kbs@shinpoong.co.kr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: * Stage 1: Single Group (Experimental drug only) * Stage 2: Parallel (Placebo control and Experimental drug)

Study Record Dates

• First Submitted: January 6, 2021
• First Posted: January 8, 2021
• Study Start: March 29, 2021
• Primary Completion: April 15, 2022
• Study Completion: April 15, 2022
• Last Updated: September 30, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

PH (4)