Pan African Clinical Trials Registry

South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202107692340845 Date of Registration: 20/07/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A Randomized, Double-Blind, Placebo-Controlled, Phase III Study to Evaluate the Safety and Efficacy of Aerosolized Novaferon + SOC vs. Placebo + SOC in Hospitalized Adult Patients with Moderate to Severe COVID-19
Official scientific title A Randomized, Double-Blind, Placebo-Controlled, Phase III Study to Evaluate the Safety and Efficacy of Aerosolized Novaferon + SOC vs. Placebo + SOC in Hospitalized Adult Patients with Moderate to Severe COVID-19
Brief summary describing the background and objectives of the trial The pandemic of COVID-19 caused by the infection from the novel coronavirus, SARS-CoV-2, continues to represent a major health challenge around the world. The current failure to contain the spread of COVID-19 is partially due to the lack of effective antiviral drugs against the SARS-CoV-2 virus. Effective antiviral drugs, if administered at an early stage in patients with mild and moderate disease are reasonably expected to help slow or stop the disease course of COVID-19, and reduce viral transmission via viral shedding (Wölfel, 2020). Effective antiviral drugs are also expected to enhance the recovery, and to slow down or help prevent disease progression, and possibly even reduce mortality in hospitalized patients. Despite the conduct of numerous clinical trials investigating both re-purposed and novel agents for COVID-19 treatments, the unmet need for an effective COVID-19 therapeutic agent remains extremely pressing. A pilot randomized clinical trial with Novaferon in 89 moderate and severe COVID-19 patients demonstrated that inhaled recombinant interferon is well tolerated. These preliminary safety and efficacy data support the further clinical investigation of Novaferon as a potential antiviral drug for COVID-19 and justify further evaluation of the efficacy of Novaferon in statistically powered double-blind randomized trials.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) NOVATION1
Disease(s) or condition(s) being studied Respiratory
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 05/09/2021
Actual trial start date
Anticipated date of last follow up 24/03/2022
Actual Last follow-up date
Anticipated target sample size (number of participants) 914
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using by using procedures such as coin-tossing or dice-rolling Central randomisation by phone/fax Masking/blinding used Care giver/Provider,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Novaferon Cohort A 20micrograms of aerosolized Novaferon Twice daily for 10 days or until discharge if it occurs before 10th day Novaferon is administered using a vibrating mesh nebulizer 40
Experimental Group Novaferon Cohort B 20micrograms of aerosolized Novaferon Twice daily for 10 days or until discharge if it occurs before 10th day Novaferon is administered using a vibrating mesh nebulizer 437
Control Group Placebo Cohort B Participants will have 10micrograms of Placebo Twice daily for 10 days or until discharge if it occurs before 10th day Placebo is administered using a vibrating mesh nebulizer 437 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Signed informed consent form by any patient capable of giving consent, or, when the patient is not capable of giving consent, by his or her legal/authorized representatives prior to initiation of any study procedures. 2. Men and women, ≥18 years of age at time of enrollment. 3. Laboratory-confirmed diagnosis of SARS-CoV-2 infection as determined by PCR, or other health authority-approved commercial assay or other validated public health assay in any specimen within 72 hours prior to randomization (point-of-care viral infection test allowable if RT-PCR test result not available only at the time of screening. Diagnosis to be confirmed by RT-PCR test on Day 1). 4. Less than or equal to 7 days from COVID-19 symptom onset to starting treatment. • Symptoms are defined as one or more of the following: cough, fever, shortness of breath, chest pain, abdominal pain, nausea/vomiting, diarrhea, body aches, weakness/fatigue, chills/sweating, headache, confusion, sore throat, runny nose/congestion, loss of taste or smell, or any other COVID-19 symptoms as determined by the Investigator. 5. Hospitalized for no more than 4 days duration, and: • i) requiring supplemental oxygen by face mask or nasal prongs, or ii) non-invasive ventilation or iii) high-flow oxygen (WHO category 4 or 5) 6. Female patients participating in this study must agree to avoid becoming pregnant and have a negative pregnancy test prior to randomization. Male patients must agree to use appropriate contraceptive methods to prevent pregnancy with their partner(s), during the study and up to post 30 days after the last dose of study drug. Female patients must be: ● unable to have children (e.g., post-menopausal*, bilateral tubal ligation, hysterectomy, bilateral oophorectomy) or where the partner is sterile (e.g., vasectomy) OR ● willing to remain abstinent (not engage in sexual intercourse for the duration of the screening period and throughout the study, and for 30 days after the last dose) OR ● willing to use two approved effective methods of birth control (male partner using condom and female partner using intrauterine device, hormonal or nonhormonal contraceptive, diaphragm plus spermicide, or contraceptive sponge) *Post-menopausal is defined as any female who is: (1) older than 55 years with amenorrhea for at least 12 consecutive months; or (2) less than 55 years with amenorrhea for at least two years 1. Known hypersensitivity or intolerance to Interferon (IFN) or Novaferon or any excipient(s) of Novaferon, including pre-existing allergy or hypersensitivity to ampicillin. 2. Currently undergoing invasive mechanical ventilation (including venous ECMO). 3. Inability to use a nebulizer with a mouthpiece. 4. ALT/AST > 5 times the Upper Limit of Normal (ULN) or a history of decompensated cirrhosis. 5. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR < 30 mL/min/ 1.73m2). 6. In the opinion of the Investigator, progression to death is imminent and inevitable within the next 48 - 72 hours, irrespective of the provision of treatment. 7. In the opinion of the Investigator, progression to mechanical ventilation is imminent and inevitable within the next 24 hours, irrespective of the provision of treatment. 8. Possibility of the patient being discharged from hospital within 24 hours. 9. Concurrent participation in other anti-COVID-19 therapeutic or interventional trials. Patients may, at the discretion of the Investigator, concurrently participate in other non-interventional COVID-19 studies. 10. Current use of other antiviral therapy (e.g., remdesivir, etc.) or other experimental therapy, including anti-inflammatory agents, convalescent plasma, ivermectin or hydroxychloroquine (see Section 9.4.1). 11. Has received or has a plan to receive within the 28-day treatment period, a SARS- CoV-2 vaccine. 12. Use of immunomodulatory drugs at, or within 3 months prior to, enrollment; use of chronic oral corticosteroids for a non-COVID-19-related condition at a dose higher than prednisone 20 mg (or equivalent) per day for the preceding 4 weeks. 13. Other known active infections or other clinical conditions (e.g., chronic obstructive pulmonary disease) that contraindicate aerosolized inhalation; coexisting pneumonia is allowed. 14. Patients with current or prior psychiatric illness, seizure disorders, retinal autoimmune disorders, pre-existing severe cardiovascular disease, and patients with prior transplants. 15. Females who are breast-feeding, lactating, pregnant or intending to become pregnant. 16. The subject has Acquired Immunodeficiency Syndrome (AIDS) or hepatitis, including hepatitis virus carriers (HBs-antigen or HCV-antibody-positive). The subject may be included in the study if HCV-antigen or HCV-RNA-negative. 80 and over: 80+ Year,Adolescent: 13 Year(s)-17 Year(s),Adult: 18 Year(s)-44 Year(s),Aged: 65 Year(s)-79 Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 105 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 01/08/2021 Scientific and Ethics Review Unit SERU
Ethics Committee Address
Street address City Postal code Country
P.O. Box 54840 00200 Off Mbagathi Road Nairobi 00000 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Cohort A Incidence, type, and severity of Adverse Events AEs, Serious Adverse Events SAEs, and Adverse Events of Special Interest AESIs Between beginning of treatment through Day 56
Primary Outcome Cohort B Proportion of patients requiring mechanical ventilation or that die Between beginning of treatment through Day 28
Secondary Outcome Cohort B Proportion of patients demonstrating clinical improvements At Day 28
Secondary Outcome Cohort B Rate of non-hospitalized, alive patients after the start of treatment At Day 28
Secondary Outcome Cohort B Mortality rate At Day 28
Secondary Outcome Cohort B Number of days hospitalized Between beginning of treatment through Day 56
Secondary Outcome Cohort B Incidence, type, and severity of AEs, SAEs, and AESIs Between beginning of treatment through Day 56
Secondary Outcome Cohort B All-cause mortality Between randomization through Day 28
Secondary Outcome Cohort B Time to clinical improvement by 2-points on eight-category WHO ordinal scale Between beginning of treatment through Day 28
Secondary Outcome Cohort B Ventilator-free days Between beginning of treatment through Day 28
Secondary Outcome Cohort B Duration of ventilation in Days Between beginning of treatment through Day 28
Secondary Outcome Cohort B Rate of alive patients without using Extracorporeal Membrane Between beginning of treatment through Day 28
Secondary Outcome Cohort B Oxygenation, ECMO, and mechanical ventilation Between beginning of treatment through Day 28
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
CREATES Strathmore University Medical Centre Ole Sangale Road off Langata Road Nairobi Kenya
KEMRI Kericho PO Box 1357 Hospital Road Kericho Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Genova Inc Rm 1603, 6 Wilmer St, Wai Wah Commercial Ctr Sai Ying Pun Hong Kong
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Genova Inc. Rm 1603, 6 Wilmer St., Wai Wah Commercial Ctr Sai Ying Pun Hong Kong Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Bernhards Ogutu ogutu6@gmail.com +254733966065 Ole Sangale Road, off Langata Road
City Postal code Country Position/Affiliation
Nairobi Kenya Principal Investigator
Role Name Email Phone Street address
Principal Investigator Isaac Tsikhutsu tsikhutsu.isaac@usamru-k.org +254722749789 PO Box 1357 Hospital Road
City Postal code Country Position/Affiliation
Kericho Kenya Principal Investigator
Role Name Email Phone Street address
Public Enquiries Qiujin Lyu qjlv@genova.cn +86136010812 Rm 1603, 6 Wilmer St, Wai Wah Commercial Ctr
City Postal code Country Position/Affiliation
Sai Ying Pun Hong Kong Senior Vice President Medical and Clinical Operation
Role Name Email Phone Street address
Scientific Enquiries Qiujin Lyu qjlv@genova.cn +861360108120 Rm 1603, 6 Wilmer St, Wai Wah Commercial Ctr
City Postal code Country Position/Affiliation
Sai Ying Pun Hong Kong Senior Vice President Medical and Clinical Operation
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Sponsor is committed to responsible data sharing regarding the clinical trials they sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. The includes requests for clinical trial data for unlicensed products and indications. Clinical Study Report,Statistical Analysis Plan,Study Protocol This will be done within 12 months of the study completion date Access is provided after a research proposal is submitted and has received approval from the Independent Review panel and after a Data Sharing Agreement is in place.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information