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Trial registered on ANZCTR


Registration number
ACTRN12622000258752
Ethics application status
Approved
Date submitted
20/01/2022
Date registered
11/02/2022
Date last updated
11/02/2022
Date data sharing statement initially provided
11/02/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
INFINiTE-CV2 Phase IIa Trial: INterFeron type 1 Intra-Nasal gel Therapy for Early treatment of SARS-CoV2 (COVID-19)
Scientific title
Phase IIa double blind randomized controlled trial of Type 1 Interferon (IFN -1)/ Hyaluronic Acid formulation for the early treatment of SARS-CoV2 infection (COVID-19)
Secondary ID [1] 306253 0
Nil known
Universal Trial Number (UTN)
U1111-1273-3552
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 324982 0
Condition category
Condition code
Respiratory 322423 322423 0 0
Other respiratory disorders / diseases
Infection 322424 322424 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Phase 2a is a double blinded randomised controlled trial involving 100 patients
- To assess whether nasal delivery of an Interferon (IFN -1)/ Hyaluronic Acid formulation improves clinical course of COVID-19 infection and viral clearance through clinical and virological measures.
- To monitor safety and acceptability of the nasal spray
- To monitor disease progression and immunological markers

Arm 1 (treatment) - Interferon + hyaluronic acid nasal spray
Route of administration: Nasal spray, both nostrils
Frequency of administration: Twice daily for five days
Dose administered: 0.28 ml sprayed into each nostril
Intervention: Test article will be 1.0ml/24M IU IFNß1a (2X (0.5ml/12M IU) Rebif 44) in 5.5ml of 3% micronized crosslinked sodium hyaluronate.
Total dose administered: The cumulative dose will be 76mcg/20.6M IU IFN in 3% hyaluronic acid (HA) suspension.

Arm 2 (placebo) - hyaluronic acid nasal spray
Route of administration: Nasal spray, both nostrils
Frequency of administration: Twice daily for five days
Dose administered: 0.28 ml sprayed into each nostril
Intervention: Solution of 3% micronized crosslinked sodium hyaluronate vehicle.
Total dose administered: The cumulative dose will be 5.6 ml of a 3% hyaluronic acid (HA) suspension.

Standardised clinical assessment (may be performed virtually) will occur at baseline (pre-randomisation, 7 days, 2 weeks, 4 weeks post-randomisation). Nasopharyngeal swabs will be obtained at day 0 and 7 to detect and quantify viral load and daily self-collected salivary samples will be collected.

Patients will be virtually contacted by a Clinical Trials Nurse to ensure compliance during the treatment program as well as follow up at trial completion
Intervention code [1] 322657 0
Treatment: Drugs
Comparator / control treatment
Arm 3 (no treatment) - surveillance (if decline participation in one of the treatment arms)

Standardised clinical assessment (may be performed virtually) will occur at baseline (pre-randomisation, 7 days, 2 weeks, 4 weeks post-randomisation). Nasopharyngeal swabs will be obtained at day 0 and 7 to detect and quantify viral load and daily self-collected salivary samples will be collected.
Control group
Active

Outcomes
Primary outcome [1] 330185 0
The affect of nasal delivery of an Interferon (IFN -1)/ Hyaluronic Acid formulation on the clinical course of COVID-19 infection determined by time to resolution of symptoms.
Timepoint [1] 330185 0
To be assessed via Total Nasal Symptom Score: The sum of 5 individual participant-assessed symptom scores using ordinal scales for each of the following symptoms: Sneezing, rhinorrhoea, nasal itching, nasal pain and nasal obstruction

Timepoints: baseline (pre-randomisation), then 7 days, 2 weeks, 4 weeks post-randomisation
Primary outcome [2] 330194 0
The affect of nasal delivery of an Interferon (IFN -1)/ Hyaluronic Acid formulation on viral clearance of COVID-19 infection
Timepoint [2] 330194 0
Determined by daily decline in viral load from Day 0 to Day 5: based on cycle threshold value from nasopharyngeal PCR.
Secondary outcome [1] 405177 0
Incidence of Hospitalization - determined during telehealth patient follow up by clinical trials nurse
Timepoint [1] 405177 0
Timeframe 28 days (outcomes measures collected at day 7, 14, 28 post randomisation)
Secondary outcome [2] 405250 0
Time to negative salivary swab based on daily saliva collections
Timepoint [2] 405250 0
Timeframe 14 days (outcomes measures collected at day 7, 14 post randomisation)
Secondary outcome [3] 405251 0
Incidence of Symptoms Compatible with COVID19 including anosmia, thrombotic or inflammatory - total nasal symptom score, pathology (full blood count, c-reactive protein)
Timepoint [3] 405251 0
Timeframe 28 days (outcomes measures collected at day 7, 14, 28 post randomisation)
Secondary outcome [4] 405252 0
Incidence of All-Cause Study Medicine Discontinuation or Withdrawal - determined during telehealth patient follow up by clinical trials nurse
Timepoint [4] 405252 0
Timeframe 14 days (outcomes measures collected at day 7, 14 post randomisation)
Secondary outcome [5] 405253 0
WHO clinical progression scale severity score at 7 and 14 days
Timepoint [5] 405253 0
Timeframe 14 days (outcomes measures collected at day 7, 14 post randomisation)
Secondary outcome [6] 405254 0
Serious adverse events and adverse events (anaphylaxis, headache, nasal bleeding, irritation or pain requiring treatment) by Individual chart review and Safety assessment by DSMB
Timepoint [6] 405254 0
Timeframe 28 days (outcomes measures collected at day 7, 14, 28 post randomisation)
Secondary outcome [7] 405255 0
Immunological markers of effective immune response (CRP, ferritin, D dimer, IL-6, LDH, troponin, interferon levels at D0, 7, 14) and serological conversion at D14
Timepoint [7] 405255 0
Timeframe 14 days (outcomes measures collected at day 14 post randomisation)
Secondary outcome [8] 406088 0
Incidence of death
Timepoint [8] 406088 0
Timeframe 28 days (outcomes measures collected at day 7, 14, 28 post randomisation)
Secondary outcome [9] 406089 0
Incidence of ED presentation - determined during telehealth patient follow up by clinical trials nurse
Timepoint [9] 406089 0
Timeframe 28 days (outcomes measures collected at day 7, 14, 28 post randomisation)

Eligibility
Key inclusion criteria
1. Males or females, aged greater than or equal to 18 years
2. Body mass index (BMI) less than or equal to 40.0 kg/m2 and greater than 15kg/m2
3. Diagnosis of SARS-CoV2 infection by PCR of nasopharyngeal swab, conducted by a NATA accredited laboratory (or international GLP equivalent) within the past 48hrs
4. enrolment within 96 hours from symptom onset (symptoms include: runny nose, headache, sore throat, fever or cough)
5. Willing and able to provide informed consent and comply with all study procedures and restrictions and the required visit schedule
6. Total Nasal Symptom Score at baseline less than 5
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Age < 18 years old
2. Concurrent enrolment in other COVID-19 trials involving investigational agents administered within the last 30 days
3. Symptoms of pre-existing or intercurrent respiratory tract illness or infection such as pneumonia, bacterial or fungal sinusitis
4. Recent sinus surgery (last 2 weeks)
5. Suspected or confirmed convalescent COVID-19, defined as any previous positive test in the prior 4 weeks before the most recent positive test
6. Inability to operate a nasal spray device
7. Inability to provide verbal consent and written consent via eREDCAP
8. Known sensitivity/allergy to interferon
9. Current use of interferon for another indication
10. Major comorbidities increasing risk of study drug including i. Hematologic malignancy, ii. Advanced (stage 4-5) chronic kidney disease or dialysis therapy (eGFR< 29 ml/min), iii. Known history of ventricular arrhythmias iv. Current use of drugs that prolong the QT interval
11. Presence or history of substance abuse, including but not limited to cocaine, opioids and marijuana
12. Current use of systemic immunosuppressive therapy that cannot be suspended for duration of trial
13. Psychiatric disorders that are considered by the treating clinician to be a contraindication to interferon therapy. [i.e., those with mild or well-controlled psychiatric disorders (e.g., mild depression) may be included]
14. Any infection requiring IV antibiotics within 4 weeks of Screening, or oral antibiotics within 2 weeks of Screening.
15. Females who are pregnant, lactating, or who have a positive pregnancy test.
The effects of Gelferon on the unborn child and on the newborn baby are not known. Because of this, participants must not participate in the research if pregnant, trying to become pregnant, breastfeeding, or planning ovum donation.
16. Known or suspected hypersensitivity or contraindication to any of the ingredients in the study drug
17. Any condition that in the opinion of investigator is a contraindication to the study
18. Regular use of topical nasal spray or nasal douching

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Phase IIa, participants and treatment nurses and clinical assessors will be blinded to treatment allocation. Both treatment arms will receive their intervention in the form of a nasopharyngeal spray.

Allocation involved contacting the holder of the allocation schedule who was "off-site". Both treatment arms will receive their intervention in the form of a nasopharyngeal spray
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will occur using an interactive voice response system, through the NHMRC randomisation service. Subjects who are enrolled into the study will be randomly allocated either to a treatment group.

Participants who wish to opt-out of the study are invited to be an observational cohort. This cohort will continue to receive normal care. Their progress will be tracked according to the same study procedure.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Phase 2a: Both primary outcomes will be recorded as continuous variables and compared using t-test reporting standard error, standard deviation and corresponding 95% confidence intervals.

The primary analysis of both primary and secondary endpoints will be according to modified intention to treat principles (all participants with data available for the endpoint will be analysed according to the treatment allocation, regardless of what treatment they received). No assumptions will be made about those with missing data.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/03/2022
Actual
Date of last participant enrolment
Anticipated
30/06/2022
Actual
Date of last data collection
Anticipated
31/07/2022
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 21523 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 36430 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 310600 0
Commercial sector/Industry
Name [1] 310600 0
IntraVital Pty Ltd
Country [1] 310600 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
IntraVital
Address
IntraVital c/o Royal Prince Alfred Hospital, 50 Missenden Road, Camperdown 2050, NSW
Country
Australia
Secondary sponsor category [1] 311992 0
None
Name [1] 311992 0
Address [1] 311992 0
Country [1] 311992 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310205 0
Belberry
Ethics committee address [1] 310205 0
123 Glen Osmond Road, Eastwood SA 5063
Ethics committee country [1] 310205 0
Australia
Date submitted for ethics approval [1] 310205 0
Approval date [1] 310205 0
02/11/2021
Ethics approval number [1] 310205 0
[REGIS Application ID:2020ETH03123]

Summary
Brief summary
The INFINiTE-CV2 Phase IIa trial aims to assess whether nasal delivery of an Interferon (IFN -1)/ Hyaluronic Acid formulation improves clinical course of COVID-19 infection and viral clearance.

This study is being performed to address an unmet urgent clinical need for a simple effective treatment for a pathogen of global health significance. It is hoped that this treatment is shown to be safe and effective with potential implications for both treatment and prevention of COVID-19.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 116858 0
A/Prof Edmund Lau
Address 116858 0
Royal Prince Alfred Hospital, 50 Missenden Rd, Camperdown NSW 2050
Country 116858 0
Australia
Phone 116858 0
+61 295158806
Fax 116858 0
Email 116858 0
[email protected]
Contact person for public queries
Name 116859 0
Edmund Lau
Address 116859 0
Royal Prince Alfred Hospital, 50 Missenden Rd, Camperdown NSW 2050
Country 116859 0
Australia
Phone 116859 0
+61 295158806
Fax 116859 0
Email 116859 0
[email protected]
Contact person for scientific queries
Name 116860 0
Edmund Lau
Address 116860 0
Royal Prince Alfred Hospital, 50 Missenden Rd, Camperdown NSW 2050
Country 116860 0
Australia
Phone 116860 0
+61 295158806
Fax 116860 0
Email 116860 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Only aggregate data will be available.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.