Clinical trial NCT04672564: Study to Evaluate Safety and Efficacy of Carrimycin for Treatment of Severe Coronavirus Disease 2019 (COVID-19) in Hospitalized Patients
Official title: A Phase 3, Randomized, Multicenter, Placebo-controlled, Double-blind Clinical Study of the Safety and Efficacy of Carrimycin for Treatment of Severe COVID-19 in Hospitalized Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Coronavirus Disease 2019
Keywords: Severe Acute Respiratory Syndrome Coronavirus 2
Safety
Novel coronavirus
Carrimycin
Remdesivir
Lead sponsor: Shenyang Tonglian Group CO., Ltd
Sponsor class: INDUSTRY
First posted: 2020-12-17
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, multicenter, placebo-controlled, double-blind clinical study in patients hospitalized due to severe Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection.

Detailed description: Eligible 300 hospitalized patients with confirmed severe SARS-CoV-2 infection will be randomly assigned (1:1) to receive 14 days treatment of 400 mg carrimycin and standard of care (SOC) or placebo and SOC.

Eligibility criteria: Inclusion Criteria:

* Patient with SARS-CoV-2 infection as determined by real time polymerase chain reaction (RT- PCR) or other commercial or public health assay in any specimen taken ≤ 4 days prior to randomization. Onset of symptoms of COVID-19 must be 14 or fewer days prior to randomization. Patient with a second SARS-CoV-2 episode after resolution of the initial infection may be enrolled if the initial infection had clearly resolved, re-infection is reconfirmed by RT-PCR and all other eligibility criteria are met
* Hospitalized patient who requires oxygen supplementation via either low-flow oxygen device (such as nasal cannula or face mask), high flow oxygen therapy (including high-flow nasal cannula), or non invasive ventilation to maintain peripheral oxygen saturation of at least 94%. The patient must have had such an oxygen requirement for 2 days or fewer at the time of Screening, and the oxygen requirement must be non-improving (worsening or stable) in the Investigator's judgement at the time of Screening and randomization
* Female patient of childbearing potential and male patient with female partner of childbearing potential must agree to use at least one primary form of contraception for the duration of the study
* Ability to provide informed consent personally, or by a legally acceptable representative if the patient is unable to do so
* Patient is willing and able to comply with all required study visits and follow up required by the protocol
* Patient must agree not to enroll in another study of an investigational agent prior to completion of Day 60 of study

Exclusion Criteria:

* Non-hospitalized patients, including those requiring home oxygen support
* Patient has a creatinine clearance \< 50 mL/min/1.73m\^2 using the modification of diet in renal disease formula
* Patient cannot take the study drug by mouth and needs to be administered by nasogastric tube at Screening.
* Patient has a known allergy to any study medication or macrolides
* Patient with known medical history of hepatitis B or, if tested, presence of hepatitis B surface antigen at Screening
* Patient has a known medical history of hepatitis C or positive hepatitis C antibody test result at Screening (if obtained)
* Patient has a positive hepatitis C RNA test result at Screening
* Patient has a known medical history of human immunodeficiency virus (HIV) infection or was seropositive for human immunodeficiency virus (if tested)
* Patient has been treated with anti-tumor therapy with immunosuppressive effects, which includes chemotherapy, biologics and hormonal therapy in the past 30 days prior to Screening
* Patient has used a macrolide in the week prior to Screening
* Patient has used antiviral drugs which are not part of SOC \< 24 hours prior to Day 1
* Patient receiving hemoperfusion or with anticipated use of hemoperfusion (including when hemoperfusion is a part of SOC)
* Patient has used the following types of medications \< 2 days prior to Day 1 and/or plans to initiate such medications during the treatment period without an appropriate alternative therapy:

  1. Narrow therapeutic index substrates of cytochrome P450 (CYP) enzymes
  2. Narrow therapeutic index substrates of major transporters: organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1, OATP1B3), organic anion transporter 1 and 3 (OAT1, OAT3), organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins 1 and 2-K (MATE1, MATE2K)
  3. Strong inhibitors and/or inducers of enzymes CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5
  4. Strong inhibitors of transporters OATP1B1 and OATP1B3
  5. Note: strong inhibitors of OAT1/OAT3, OCT2 and MATE1/MATE2K should be avoided when possible, but when unavoidable investigators may assess the risks and benefits and to continue treatment with such medications under close observation for adverse events
* Patient has consumed foods and/or used herbal medicines with strong CYP3A4 or CYP3A5 effects
* Patient who, in the judgment of the Investigator, will be unlikely or unable to comply with the requirements of this protocol through Day 60
* Female patient who is pregnant or breastfeeding
* Critical patient with a life expectancy \< 48 hours
* Patient who has received an organ transplant in the past 6 months prior to Screening or is on the waiting list for organ transplantation
* Patient with evidence of multiorgan failure (defined as two or more organs failing) or septic shock
* Patient requiring mechanical ventilation or extracorporeal membrane oxygenation at Screening
* Patient has a mean corrected QT interval using Fridericia's formula (QTcF) of \> 450 msec (for male patients) and \> 470 msec (for female patients) at Screening
* Patient who has a history of alcohol abuse within 3 months prior to the study as judged by the Investigator

Primary outcomes:
measure: Time to patient not requiring supplemental oxygen up to 28 days after randomisation
timeFrame: Up to Day 28
Secondary outcomes:
measure: Time to recovery based on 8-category ordinal scale
timeFrame: From screening Day (Day -4 to Day -1) until Day 28
measure: Time to recovery based on the Breathlessness, Cough and Sputum Scale (BCSS)
timeFrame: From screening Day (Day -4 to Day -1) until Day 28
measure: Time to symptom improvement
timeFrame: From screening Day (Day -4 to Day -1) until Day 28
measure: Length of hospital stay (in days)
timeFrame: From Screening Day (Day -4 to Day -1) until Day 60 or Early Withdrawal
measure: Time to discharge (in days)
timeFrame: From screening Day (Day -4 to Day -1) until Day 60 and at Early Withdrawal
measure: Number of patients with all cause mortality at Days 14 and 28
timeFrame: At Days 14 and 28
measure: Changes from baseline in sequential organ failure assessment (SOFA) score
timeFrame: From baseline (Day -4 to Day -1) Days 3, 7, 10, 14 and 28 after treatment
measure: Percentage of patients who reach level 2 or lower at Day 28 on the 8 category ordinal scale
timeFrame: From screening Day (Day -4 to Day -1) until Day 28
measure: Mean changes in BCSS score during the study period
timeFrame: From screening Day (Day -4 to Day -1) until Day 28
measure: Change from baseline in respiratory rate
timeFrame: From screening Day (Day -4 to Day -1) until Day 60 and at Early Withdrawal
measure: Change from baseline in temperature
timeFrame: From screening Day (Day -4 to Day -1) until Day 60 and at Early Withdrawal
measure: Number of patients with adverse event (AEs) and Serious adverse events (SAEs)
timeFrame: From screening Day (Day -4 to Day -1) until Day 28 and until Day 60
Other outcomes:
Locations:
city: Amarillo
country: United States
facility: PharmaTex Research, LLC
state: Texas
city: La Plata
country: Argentina
facility: Instituto Médico Platense
state: Buenos Aires
city: Campinas
country: Brazil
facility: Instituto de Pesquisa Clínica de Campinas
state: São Paulo
city: São José do Rio Preto
country: Brazil
facility: Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto - Hospital de Base
state: São Paulo
city: Guadalajara
country: Mexico
facility: Nuevo Hospital Civil de Guadalajara "Juan I. Menchaca"
state: Jalisco
city: Mérida
country: Mexico
facility: EME RED Hospitalaria
state: Yucatán
city: Mérida
country: Mexico
facility: Hospital Dr. Agustin O'Horan
state: Yucatán
city: Iloilo City
country: Philippines
facility: St. Paul's Hospital of Iloilo, Inc.
state: Iloilo
city: Makati City
country: Philippines
facility: Makati Medical Center - Infectious Diseases
state: National Capital Region
city: Pasay
country: Philippines
facility: San Juan De Dios Hospital
state: National Capital Region
city: Quezon City
country: Philippines
facility: Veterans Memorial Medical Center
state: National Capital Region
city: Quezon
country: Philippines
facility: Quirino Memorial Medical Center
state: National Capital Region
city: Chernihiv
country: Ukraine
facility: Chernihivska miska likarnia #2
state: Chernihivs'ka Oblast'
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Central City Clinical Hospital
state: Ivano-Frankivs'ka Oblast'
city: Ivano-Frankivsk
country: Ukraine
facility: Oblasnyi klinichnyi ftyziopulmonolohichnyi tsentr
state: Ivano-Frankivs'ka Oblast'
city: Poltava
country: Ukraine
facility: Komunalne Pidpryiemstvo "Poltavska Oblasna Klinichna Infektsiina Likarnia" Poltavskoi Oblasnoi Rady
state: Poltavs'ka Oblast'
city: Lutsk
country: Ukraine
facility: Volyn Regional Clinical Hospital
state: Volyns'ka Oblast'
Study officials:
References: