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.
arm, open-label design. Artecom® will be administered orally once a day for 3 consecutive
days. All subjects will be evaluated for efficacy and safety for 28 days.
After the completion of the final participant in Stage 1, the DSMB will review the safety
data from Stage 1 and determine whether to proceed to Stage 2.
blinded manner to receive either Artecom® or placebo (1:1 ratio) orally once a day for 3
consecutive days. All subjects will be evaluated for efficacy and safety for 28 days.
A second DSMB meeting and review of all available blinded safety data will occur after 191
participants have completed Day 28. A final DSMB meeting will be held after the completion of
a study assessment by the last participant.
Drug: Artecom® (pyronaridine-artesunate)
* Participant body weight (Artecom® dose)
≥ 65kg (Artecom® 4 tablets: Pyronaridine 720mg/ Artesunate 240mg)
≥ 45kg and < 65kg (Artecom® 3 tablets: Pyronaridine 540mg/ Artesunate 180mg)
Other Name: Pyramax® (pyronaridine-artesunate)
Drug: Placebo
* Participant body weight (Placebo dose)
≥ 65kg (Placebo 4 tablets)
≥ 45kg and < 65kg (Placebo 3 tablets)
Inclusion Criteria:
1. Male and female adults age (≥19 years at the time of informed consent)
2. Body weight (≥ 45 kg at Screening)
3. 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.
4. 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.)
Exclusion Criteria:
1. Participants with clinically significant cardiovascular disease (including arrhythmia,
corrected QT interval prolongation [QTcF> 470 msec for females, or >450 msec for
males, at Screening])
2. Participants with clinically significant anemia (Hemoglobin <8.0 g/dL)
3. Participants who have hypersensitivity to main ingredients (pyronaridine
tetraphosphate, artesunate) and any excipient in the IP
4. 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)
5. 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
6. Participants with severe renal impairment (estimated glomerular filtration rate ≤30
mL/min/1.73 m2)
7. 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
8. 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)
9. 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.
10. 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.
11. Pregnant or lactating at Screening or planning to become pregnant (self or partner) at
any time during the study, including the follow-up period.
12. 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.
13. Participants who the Investigator has deemed inappropriate for inclusion in this study
for any other reason.
14. 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.
De La Salle University Medical Center
Dasmariñas, Gov, D. Mangubat St, 4114 Cavite, Philippines
The Medical City
Pasig City, Ortigas Avenue, Barangay Ugong, Metro Manila, Philippines
Lung Center of the Philippines
Quezon City, Quezon Avenue, Quezon City, 1100 Philippines, Philippines
Philippine General Hospital
Manila, Taft Ave, Ermita, Manila, 1000 Metro, Philippines
Belen L Dofitas, MD, PhD
+63-917-629-4329
belendofitas@gmail.com
Byung Su Kim, MS
+82-31-348-9354
135kbs@shinpoong.co.kr
Belen L Dofitas, MD, PhD, Principal Investigator
Philippine General Hospital, University of the Philippines