Study to Evaluate Safety and Efficacy of Carrimycin for Treatment of Severe Coronavirus Disease 2019 (COVID-19) in Hospitalized Patients

Sponsor

Shenyang Tonglian Group CO., Ltd (Industry)

Overall Status

Suspended

CT.gov ID

NCT04672564

Collaborator

(none)

300

Enrollment

Locations

Arms

19.9

Anticipated Duration (Months)

5.6

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coronavirus Disease 2019	Drug: Carrimycin Drug: Placebo	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 30, 2021

Anticipated Primary Completion Date :

Nov 25, 2022

Anticipated Study Completion Date :

Nov 25, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Carrimycin Patients will receive oral dose of 400 mg carrimycin once-daily and SOC for 14 days.	Drug: Carrimycin Carrimycin (400 mg) will be given once-daily for 14 days (2 x 200 mg tablets) after a meal, if a patient experiences an eating problem, carrimycin will be taken without food.
Placebo Comparator: Placebo Patients will receive oral dose of Placebo once-daily and SOC for 14 days.	Drug: Placebo Placebo will be given once-daily for 14 days (2 tablets) after a meal, if a patient experiences an eating problem, placebo will be taken without food.

Arm

Intervention/Treatment

Experimental: Carrimycin

Patients will receive oral dose of 400 mg carrimycin once-daily and SOC for 14 days.

Drug: Carrimycin

Carrimycin (400 mg) will be given once-daily for 14 days (2 x 200 mg tablets) after a meal, if a patient experiences an eating problem, carrimycin will be taken without food.

Placebo Comparator: Placebo

Patients will receive oral dose of Placebo once-daily and SOC for 14 days.

Drug: Placebo

Placebo will be given once-daily for 14 days (2 tablets) after a meal, if a patient experiences an eating problem, placebo will be taken without food.

Outcome Measures

Primary Outcome Measures

Time to patient not requiring supplemental oxygen up to 28 days after randomisation [Up to Day 28]
To evaluate the efficacy of carrimycin with SOC compared to placebo with SOC in patients hospitalized with severe SARS-CoV-2 pneumonia. Patients must have remained off of supplemental oxygen for at least 48 hours and remain off of oxygen until Day 28

Secondary Outcome Measures

Time to recovery based on 8-category ordinal scale [From screening Day (Day -4 to Day -1) until Day 28]
To describe the difference in time to pre-defined symptom improvement compared to placebo, based on 8-category ordinal scale. Time to recovery is defined as time point when a patient reaches level 3 or lower on the 8-Category ordinal scale and does not return to a level > 3 during the 28-day period. The 8-Category ordinal scale score ranges from 1 to 8. Score 1: Not hospitalized, no limitations on activities; 2: Not hospitalized, limitation on activities, home oxygen requirement or both; 3: Hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care; 4: Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care; 5: Hospitalized, requiring supplemental oxygen; 6: Hospitalized, requiring noninvasive ventilation or high flow oxygen devices; 7: Hospitalized, receiving invasive mechanical ventilation or extracorporeal membrane oxygenation and score 8: Death. Higher scores indicate worse outcome.
Time to recovery based on the Breathlessness, Cough and Sputum Scale (BCSS) [From screening Day (Day -4 to Day -1) until Day 28]
To describe the difference in time to pre-defined symptom improvement compared to placebo based on the BCSS. The BCSS is a three-item questionnaire rating breathlessness, cough and sputum on a 5-point Likert scale from 0 (no symptoms) to 4 (severe symptoms). A reduction in the mean total BCSS score represents a substantial symptomatic improvement.
Time to symptom improvement [From screening Day (Day -4 to Day -1) until Day 28]
To describe the difference in time to pre-defined symptom improvement compared to placebo, based on the BCSS. Time to symptom improvement can be considered when the score of a patient has a reduction of 1 with 2 consecutive ratings on the BCSS. The BCSS is a three-item questionnaire rating breathlessness, cough and sputum on a 5-point Likert scale from 0 (no symptoms) to 4 (severe symptoms). A reduction in the mean total BCSS score represents a substantial symptomatic improvement.
Length of hospital stay (in days) [From Screening Day (Day -4 to Day -1) until Day 60 or Early Withdrawal]
To evaluate length of hospital stay between patients receiving carrimycin vs placebo.
Time to discharge (in days) [From screening Day (Day -4 to Day -1) until Day 60 and at Early Withdrawal]
To evaluate time to discharge between patients receiving carrimycin vs placebo.
Number of patients with all cause mortality at Days 14 and 28 [At Days 14 and 28]
To evaluate mortality rates between patients receiving carrimycin vs placebo.
Changes from baseline in sequential organ failure assessment (SOFA) score [From baseline (Day -4 to Day -1) Days 3, 7, 10, 14 and 28 after treatment]
To evaluate the improvement for specific clinical parameters including fever, respiratory rate, oxygen saturation, breathlessness, cough and sputum production. The SOFA score ranges from 0 to 4. Lower score predicts better organ functioning and higher score represents severe organ failure.
Percentage of patients who reach level 2 or lower at Day 28 on the 8 category ordinal scale [From screening Day (Day -4 to Day -1) until Day 28]
The 8-Category ordinal scale score ranges from 1 to 8. Score 1: Not hospitalized, no limitations on activities; 2: Not hospitalized, limitation on activities, home oxygen requirement or both; 3: Hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care; 4: Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care; 5: Hospitalized, requiring supplemental oxygen; 6: Hospitalized, requiring noninvasive ventilation or high flow oxygen devices; 7: Hospitalized, receiving invasive mechanical ventilation or extracorporeal membrane oxygenation and score 8: Death. Higher scores indicate worse outcome.
Mean changes in BCSS score during the study period [From screening Day (Day -4 to Day -1) until Day 28]
To evaluate the improvement for specific clinical parameters including breathlessness, cough and sputum production. The BCSS is a three-item questionnaire rating breathlessness, cough and sputum on a 5-point Likert scale from 0 (no symptoms) to 4 (severe symptoms). A reduction in the mean total BCSS score represents a substantial symptomatic improvement.
Change from baseline in respiratory rate [From screening Day (Day -4 to Day -1) until Day 60 and at Early Withdrawal]
To evaluate the improvement for specific clinical parameters including respiratory rate.
Change from baseline in temperature [From screening Day (Day -4 to Day -1) until Day 60 and at Early Withdrawal]
To evaluate the improvement for specific clinical parameters including fever.
Number of patients with adverse event (AEs) and Serious adverse events (SAEs) [From screening Day (Day -4 to Day -1) until Day 28 and until Day 60]
To evaluate the safety and tolerability of the carrimycin and to describe the safety profile of treatments as reflected by AEs and SAEs.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Narrow therapeutic index substrates of cytochrome P450 (CYP) enzymes
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)
Strong inhibitors and/or inducers of enzymes CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5
Strong inhibitors of transporters OATP1B1 and OATP1B3
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Central DuPage Hospital	Winfield	Illinois	United States	60190
2	PharmaTex Research, LLC	Amarillo	Texas	United States	79109
3	Instituto Médico Platense	La Plata	Buenos Aires	Argentina	B1900AVG
4	Clínica Monte Grande	Monte Grande	Buenos Aires	Argentina	B1842DID
5	Instituto Medico Rio Cuarto	Rio Cuarto	Córdoba	Argentina	5000
6	Hospital General de Agudos Donación F. Santojanni	Buenos Aires		Argentina	C1159AEA
7	Sanatorio Mayo Privado SA	Córdoba		Argentina	5000
8	Hospital Cardio Pulmonar	Salvador	Bahia	Brazil	40170-130
9	Instituto Goiano de Oncologia e Hematologia - INGOH	Aparecida de Goiânia	Goiás	Brazil	74905-410
10	Hospital Municipal de Aparecida de Goiânia - HMAP	Aparecida de Goiânia	Goiás	Brazil	74936-600
11	Hospital Luxemburgo - Associação Mário Penna	Belo Horizonte	Minas Gerais	Brazil	30380-472
12	Instituto de Pesquisa Clínica de Campinas	Campinas	São Paulo	Brazil	13060-080
13	Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto - Hospital de Base	São José do Rio Preto	São Paulo	Brazil	15090-000
14	Rede Dor São Luiz S.A. - Hospital São Luiz Jabaquara	São Paulo		Brazil	04321-120
15	Corporación para Estudios en Salud Clinica "CES"	Medellin	Antioquia	Colombia	50012
16	Clinica SOMER	Rionegro	Antioquia	Colombia	54040
17	Clinica de la Mujer	Bogotá	Cundinamarca	Colombia	110221
18	Hospital Universitario Clínica San Rafael	Bogota		Colombia	110411
19	Paarthiv Lung Care Centre - Internal Medicine	Hyderabad	Andhra Pradesh	India	500018
20	King George Hospital	Visakhapatnam	Andhra Pradesh	India	530002
21	Unity Hospital	Surat	Gujarat	India	395010
22	K.L.E.S. Dr. Prabhakar Kore Hospital & Medical Research Cent	Belgaum	Karnataka	India	590010
23	Adichunchanagiri Hospital and Research Centre	Mandya	Karnataka	India	571418
24	Government Medical College - Department of Internal Medicine	Nagpur	Maharashtra	India	440009
25	Suretech Hospital and Research Centre - Internal Medicine	Nagpur	Maharashtra	India	440012
26	Shalinitai Meghe Hospital & Research centre	Nagpur	Maharashtra	India	441110
27	Universal Hospital	Pune	Maharashtra	India	4110011
28	Saveetha Medical College & Hospital	Chennai	Tamil Nadu	India	602105
29	St.Theresa's Hospital	Hyderabad	Telangana	India	500018
30	Nuevo Hospital Civil de Guadalajara "Juan I. Menchaca"	Guadalajara	Jalisco	Mexico	44340
31	Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Nuevo Leon	Nuevo León	Mexico	64460
32	Hospital General de Culiacán	Culiacán	Sinaloa	Mexico	80020
33	Kohler & Milstein Research	Merida	Yucatán	Mexico	97070
34	EME RED Hospitalaria	Mérida	Yucatán	Mexico	97000
35	Hospital Español de Veracruz	Veracruz		Mexico	91700
36	Complejo Hospitalario San Pablo	Lima		Peru	15023
37	Clinica Ricardo Palma	Lima		Peru	15036
38	Hospital Central FAP	Lima		Peru	15046
39	De La Salle Health Sciences Institute	Cavite City	Cavite	Philippines	4114
40	St. Paul's Hospital of Iloilo, Inc.	Iloilo City	Iloilo	Philippines	5000
41	Makati Medical Center - Infectious Diseases	Makati City	National Capital Region	Philippines	1229
42	San Juan De Dios Hospital	Pasay	National Capital Region	Philippines	1300
43	Veterans Memorial Medical Center	Quezon City	National Capital Region	Philippines	0870
44	St. Lukes Hospital	Quezon City	National Capital Region	Philippines	1112
45	Quirino Memorial Medical Center	Quezon	National Capital Region	Philippines	1109
46	Chernihivska miska likarnia #2	Chernihiv	Chernihivs'ka Oblast'	Ukraine	14034
47	Ivano-Frankivsk Central City Clinical Hospital	Ivano-Frankivsk	Ivano-Frankivs'ka Oblast'	Ukraine	76018
48	Oblasnyi klinichnyi ftyziopulmonolohichnyi tsentr	Ivano-Frankivsk	Ivano-Frankivs'ka Oblast'	Ukraine	76018
49	Municipal Non-Profit Enterprise of Kharkiv Regional Council	Kharkiv	Kharkivs'ka Oblast'	Ukraine	61096
50	Kharkiv National Medical University	Kharkiv	Kharkivs'ka Oblast'	Ukraine	61124
51	Kyivska miska likarnia #8	Kyiv	Kyïv	Ukraine	04201
52	Komunalne Pidpryiemstvo "Poltavska Oblasna Klinichna Infektsiina Likarnia" Poltavskoi Oblasnoi Rady	Poltava	Poltavs'ka Oblast'	Ukraine	36011
53	Vinnytskyi natsionalnyi medychnyi universytet imeni M.I. Pyr	Vinnytsia	Vinnyts'ka Oblast	Ukraine	21029
54	Volyn Regional Clinical Hospital	Lutsk	Volyns'ka Oblast'	Ukraine	43005