Protocol summary

Study aim
The evaluation of safety and efficacy of Pembrolizumab (CinnaGen Co, Iran) in patients with COVID-19
Design
This is a phase II, open-label, and single-arm study with the sample size of 62 patients.‎
Settings and conduct
This phase-II, single-arm, open-label, two-centered (Iran) clinical trial will be conducted in patients with COVID-19 with a follow-up duration of at least 7 days. Pembrolizumab will be administered to the eligible patients on day 1, duration of treatment of standard of care is due to physician. The outcomes will be investigated within at least 7 days.
Participants/Inclusion and exclusion criteria
Inclusion:patients aged 18 – 75 years while signing ICF, Patient with confirmed diagnosis of 2019-ncov infection, Clinical manifestation of:1- SpO2≤ 93% while resting and 2- Bilateral pulmonary involvement in radiographic results and 3- IL-6 < 7 pg/mL and 4- CRP < 50 mg/L and 5- Lymphocyte count > 800 cells/µL and 6- Ferritin < 300 µg/L, Adequate organ and marrow function Exclusion: Critical patients, hepatitis B or C, HIV or active tuberculosis, Patient with COPD and ILD, The underlying disease is very serious and the expected survival time is less than 6 months, Active hepatic disease and hepatic failure, Active or history of autoimmune disease, Patients with myocarditis, History of transplantation, Received radiotherapy and chemotherapy for malignant tumor within 6 months, Has received or will receive a live vaccine within 30 days prior to the first administration, Hypersensitivity, 90 days of retinal detachment or eye surgery, Participated in other clinical intervention trials within the last 3 months, Pregnancy and breastfeeding
Intervention groups
Intravenous pembrolizumab 200 mg in combination with standard of care
Main outcome variables
Incidence of death during the study

General information

Reason for update
Acronym
IRCT registration information
IRCT registration number: IRCT20150303021315N19
Registration date: 2020-05-27, 1399/03/07
Registration timing: prospective

Last update: 2020-05-27, 1399/03/07
Update count: 0
Registration date
2020-05-27, 1399/03/07
Registrant information
Name
Nassim Anjidani
Name of organization / entity
Orchid Pharmed
Country
Iran (Islamic Republic of)
Phone
+98 21 4347 3000
Email address
amini@orchidpharmed.com
Recruitment status
recruiting
Funding source
Expected recruitment start date
2020-06-06, 1399/03/17
Expected recruitment end date
2020-11-05, 1399/08/15
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
The evaluation of safety and efficacy of Pembrolizumab (CinnaGen Co, Iran) in patients with COVID-19
Public title
Pembrolizumab (CinnaGen Co, Iran) in COVID-19
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Male or female patients aged 18 – 75 years while signing ICF Able and willing to sign the informed consent Patient with confirmed diagnosis of 2019-ncov infection based on RT-PCR and/or radiographic results Clinical manifestation of:1- SpO2≤ 93% while resting and 2- Bilateral pulmonary involvement in radiographic results and 3- IL-6 < 7 pg/mL and 4- CRP < 50 mg/L and 5- Lymphocyte count > 800 cells/µL and 6- Ferritin < 300 µg/L Adequate organ and marrow function
Exclusion criteria:
Critical patients defined as: 1- respiratory failure which requiring mechanical ventilation or 2- Shock or 3- combined with other organ failure, need to be admitted to ICU Patients with hepatitis B or C, HIV or active tuberculosis Patient with COPD or end-stage lung disease requires home oxygen therapy Patients with interstitial lung disease (ILD) The underlying disease is very serious and the expected survival time is less than 6 months (such as advanced malignant tumor) Active hepatic disease and hepatic failure Active or history of autoimmune disease Patients with myocarditis History of organ, bone marrow or hematopoietic Stem Cell transplantation Received radiotherapy and chemotherapy for malignant tumor within 6 months Has received or will receive a live vaccine within 30 days prior to the first administration of study medication. Seasonal flu vaccines that do not contain a live virus are permitted Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody Is receiving systemic steroid therapy < 3 days prior to the first dose of trial treatment or receiving any other form of immunosuppressive medication Major surgery within 3 weeks before randomization Hypersensivity to pembrolizumab, standard of care or any components of the formulation 90 days of retinal detachment or eye surgery Permanent blindness in one eye, history of iritis, endophthalmitis, scleral inflammation or retinitis Participated in other clinical intervention trials within the last 3 months Pregnancy and breastfeeding The competent physician considered it inappropriate to participate in the study
Age
From 18 years old to 70 years old
Gender
Both
Phase
2
Groups that have been masked
No information
Sample size
Target sample size: 62
Randomization (investigator's opinion)
N/A
Randomization description
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Single
Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
National Research Institute of Tuberculosis and Lung Diseases Masih Daneshvari
Street address
Masih Daneshvari Hospital, Darabad Avenue, Shahid Bahonar roundabout, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1956944413
Approval date
2020-05-21, 1399/03/01
Ethics committee reference number
IR.SBMU.NRITLD.REC.1399.117

Health conditions studied

1

Description of health condition studied
COVID-19
ICD-10 code
U07.1
ICD-10 code description
COVID-19

Primary outcomes

1

Description
Incidence of death during the study
Timepoint
at least 7 days
Method of measurement
Recording the incidence of death

Secondary outcomes

1

Description
Days of hospitalization
Timepoint
Daily
Method of measurement
Counting the days of hospitalization

2

Description
Changing patient’s condition to critical (Critical patients defined as:1- respiratory failure which requiring mechanical ventilation or 2- Shock or 3- combined with other organ failure, need to be admitted to ICU)
Timepoint
Daily
Method of measurement
Examination and diagnosis by competent physician

3

Description
Percentage of patients with negative RT-PCR for nCoV-2019
Timepoint
Screening day, day 7 or discharge day
Method of measurement
Diagnostic kit

4

Description
Changes in percentage of SpO2 during study
Timepoint
Several times in a day
Method of measurement
Oxygen saturation test

5

Description
The lesions of the pulmonary segment numbers involved in pulmonary graphy
Timepoint
Screening day, day 7 or discharge day
Method of measurement
CT-scan or chest x-ray

6

Description
Changes in lymphocyte count
Timepoint
Daily
Method of measurement
Laboratory Test

7

Description
Changes in neutrophil count
Timepoint
Daily
Method of measurement
Laboratory Test

8

Description
Changes in CRP level
Timepoint
Daily
Method of measurement
Laboratory Test

9

Description
Peripheral edema
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

10

Description
Cardiac arrhythmia
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

11

Description
Fatigue
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

12

Description
Pain
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

13

Description
Headache
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

14

Description
Pruritus
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

15

Description
Skin rash
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

16

Description
Vitiligo
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

17

Description
Hyperglycemia
Timepoint
Daily
Method of measurement
Laboratory test

18

Description
Hyperalbuminemia
Timepoint
every other day
Method of measurement
Laboratory test

19

Description
Hypocalcemia
Timepoint
every other day
Method of measurement
Laboratory test

20

Description
Hyponatremia
Timepoint
every other day
Method of measurement
Laboratory test

21

Description
Hypophosphatemia
Timepoint
every other day
Method of measurement
Laboratory test

22

Description
Hypocalcemia
Timepoint
every other day
Method of measurement
Laboratory test

23

Description
Hypokalemia
Timepoint
every other day
Method of measurement
Laboratory test

24

Description
Hypogycemia
Timepoint
Daily
Method of measurement
Laboratory test

25

Description
Hypercalcemia
Timepoint
every other day
Method of measurement
Laboratory test

26

Description
Hyperkalemia
Timepoint
every other day
Method of measurement
Laboratory test

27

Description
Hypothyroidism
Timepoint
Screening day, day 7 or discharge day
Method of measurement
Laboratory test

28

Description
Diarrhea
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

29

Description
Decreased appetite
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

30

Description
Constipation
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

31

Description
Abdominal pain
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

32

Description
Nausea
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

33

Description
Vomiting
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

34

Description
Urinary tract infection
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

35

Description
Hematuria
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

36

Description
Anemia
Timepoint
Daily
Method of measurement
Laboratory test

37

Description
Leukopenia
Timepoint
Daily
Method of measurement
Laboratory test

38

Description
Thrombocytopenia
Timepoint
Daily
Method of measurement
Laboratory test

39

Description
Hemorrhage
Timepoint
In each visit by physician
Method of measurement
Clinical evaluation

40

Description
Increased INR
Timepoint
every other day
Method of measurement
Laboratory test

41

Description
Prolonged partial thromboplastin time
Timepoint
every other day
Method of measurement
Laboratory test

42

Description
Increased serum alkaline phosphatase
Timepoint
every other day
Method of measurement
Laboratory test

43

Description
Increased serum alanine aminotransferase
Timepoint
every other day
Method of measurement
Laboratory test

44

Description
Increased serum aspartate aminotransferase
Timepoint
every other day
Method of measurement
Laboratory test

45

Description
Infection
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

46

Description
Masculoskeletal pain
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

47

Description
Back pain
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

48

Description
Asthenia
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

49

Description
Increased serum creatinine
Timepoint
every other day
Method of measurement
Laboratory test

50

Description
Upper respiratory tract infection
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

51

Description
Cough
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

52

Description
Dyspnea
Timepoint
In each visit by physician
Method of measurement
Clinical Evaluation

Intervention groups

1

Description
200 mg intravenous pembrolizumab (produced by CinnaGen company) single dose on day 1, in combination with standard of care during treatment
Category
Treatment - Drugs

Recruitment centers

1

Recruitment center
Name of recruitment center
Massih Daneshvari Hospital
Full name of responsible person
Payam Tabarsi
Street address
Darabad, Shahid Bahonar Ave,Tehran
City
Tehran
Province
Tehran
Postal code
1956944413
Phone
+98 21 2712 2037
Fax
+98 21 2610 9590
Email
payamtabarsi@yahoo.com

2

Recruitment center
Name of recruitment center
Namazi Hospital
Full name of responsible person
Alireza Rezvani
Street address
Zand Street, Namaz Square, Shiraz, Fars, Iran
City
Shiraz
Province
Fars
Postal code
748596
Phone
+98 71 3647 4332
Email
Dr.rezvani@hotmail.com

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
CinnaGen Company
Full name of responsible person
Nasim Anjidani
Street address
CinnaGen research and production Company. Simin Dasht Industrial Park, Karaj, Alborz, Iran
City
Karaj
Province
Alborz
Postal code
6670337 263 98
Phone
+98 26 3667 0334
Email
cinnagen@cinnagen.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
CinnaGen Company
Proportion provided by this source
100
Public or private sector
Private
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Industry

Person responsible for general inquiries

Contact
Name of organization / entity
Orchid Phramed Co.
Full name of responsible person
Nasim Anjidani
Position
Pharmacist (PharmD), Medical Manager
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
No. 42, Atar St, Attar Sq
City
Tehran
Province
Tehran
Postal code
1468813112
Phone
+98 21 4347 3000
Email
anjidani.n@orchipharmed.com

Person responsible for scientific inquiries

Contact
Name of organization / entity
Shahid Beheshti University of Medical Sciences
Full name of responsible person
Payam Tabarsi
Position
Associate professor
Latest degree
Medical doctor
Other areas of specialty/work
Infectious diseases
Street address
Darabad, Shahid Bahonar Ave, Massih Daneshvari Hospital
City
Tehran
Province
Tehran
Postal code
1956944413
Phone
+98 21 2610 5050
Email
payamtabarsi@yahoo.com

Person responsible for updating data

Contact
Name of organization / entity
Orchid Pharmed Co.
Full name of responsible person
Nasim Anjidani
Position
Pharm.D./Clinical trial Department Manager
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
No. 42, Atar St, Attar Sq
City
Tehran
Province
Tehran
Postal code
1651655
Phone
009843473000
Email
anjidani.n@orchipharmed.com

Sharing plan

Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available
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