VOXVOGANAN for COVID-19 | COVID-like illness

Inclusion criteria

• {"criterion_text":"- Participant is ≥18 years of age on the day of inclusion; if people aged <18 years are suitable for inclusion in the evaluation of an IP, then this will be described and justified in the relevant intervention specific appendix\n- NONS and SN Spray specific: For women of Child bearing potential, prepared to use an effective method of contraception or abstinence for 30 days before and after inclusion.\n- NONS and SN Spray specific: For women of child-bearing potential, a negative urine pregnancy test.\n- LTX-109 specific: Inclusion within 3 days since onset of respiratory symptoms\n- Presence of at least two symptoms suggestive of COVID-19 or COVID-like-illness, one respiratory (cough, sore throat, running or congested nose or sinuses, shortness of breath) and one systemic (fever, feeling feverish, sweats/chills or shivering, low energy or tiredness, headache, muscle, joint or body aches, loss of taste and/or smell).\n- Judged by recruiting medically qualified clinician or delegate that the illness is due to a respiratory infection\n- Onset of symptoms less than x days (x will be specified in the ISA\n- Willing and able to give informed consent for participation in the study\n- Willing and able to comply with all trial procedures (including availability of freezer at participant’s home to store self-collected swabs).\n- Any additional eligibility criteria relevant to women of child-bearing potential (WOCBP), including current pregnancy or breastfeeding will be specified in the ISA. Participants of childbearing potential are defined as participants who are potentially fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. Highly effective contraception methods include sterilisation, combined oestrogen and progestogen containing hormonal contraception (oral, intravaginal, transdermal), progestogen-only hormonal contraception (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner (provided that partner is the sole sexual partner of the WOCBP trial participant, and that the vasectomised partner has received medical assessment of the surgical success). If women have been abstinent of heterosexual sex for the 30 days before enrolling in the trial and will agree to continue to be abstinent of heterosexual sex for a further 30 days after the end of IP intake, where this is in line with their preferred and usual lifestyle, this would also count as effective contraception\n- NONS and SN Spray specific: Onset of symptoms within 3 days"}

Exclusion criteria

• {"criterion_text":"- Requiring admission to the hospital on the day of inclusion.\n- NONS and SN Spray specific: Current of history of moderate to severe epistaxis or hereditary hemorrhagic telangiectasia\n- NONS and SN Spray specific: History of cerebral spinal fluid leaks via the sinuses/nose\n- Any personnel involved in the study\n- NONS and SN Spray specific: Recent nasal fracture, nasal tumors, nasal masses, meningoencephalocele, and/or nasal surgery within the previous 2 weeks\n- LTX-109 specific: Any known nasal anatomical anomalies\n- NONS and SN Spray specific: Using any of the contradicted agents within 7 days before screening: o NO donors/derivatives: isosorbide dinitrate, isosorbide mononitrate, nitroglycerine/glyceryl trinitrate, nitroprusside, nicorandil. o Phosphodiesterase inhibitors: avanafil, sildenafil, tadalafil, vardenafil. o Guanylate cyclase activators: riociguat, linaclotide.\n- Known allergies or hypersensitivities to any of the components used in the formulation of the IP, or the control product.\n- Any disease, condition, or disorder, or language barrier that precludes participation in the trial, in the opinion of the person GP or delegate checking eligibility and taking consent.\n- NONS and SN Spray specific: Known to be currently pregnant or breastfeeding\n- NONS and SN Spray specific: Known glucose-6-phosphate-dehydrogenase (G6PD) deficiency.\n- NONS and SN Spray specific: Current of history of moderate to severe epistaxis or hereditary hemorrhagic telangiectasia\n- Currently participating in a trial of a pharmacological treatment."}

Primary endpoints

• {"endpoint_text":"- Time to first self-report of feeling recovered from symptoms related to COVID-19 or COVID-like-illness.","definition_or_measurement_approach":"Measured as time (days) from inclusion to first participant self-report of feeling recovered (participant-reported outcome). For Phase IIb/III evaluation as specified in relevant intervention-specific appendix."}
• {"endpoint_text":"- Viral clearance and potentially reduction in viral load and/or impact on biomarkers of illness severity (for Phase IIa type evaluation) from baseline to ISA-specified days between day 1 and 14","definition_or_measurement_approach":"Measured as viral clearance and reduction in viral load and biomarker changes from baseline to ISA-specified days between Day 1 and Day 14; specifics and exact days are defined in the intervention-specific appendix (ISA)."}
• {"endpoint_text":"- LTX-109 specific: Viral clearance by LTX-109 nasal spray (0.5% w/w) measured at Day 3 after inclusion as compared to placebo nasal spray (0% LTX-109)","definition_or_measurement_approach":"Measured viral clearance at Day 3 post-inclusion comparing LTX-109 (0.5% w/w) nasal spray versus placebo nasal spray (0% LTX-109)."}

Secondary endpoints

• {"endpoint_text":"- Time to first self-report of return to usual daily activity.","definition_or_measurement_approach":"Participant-reported time (days) to first report of return to usual daily activities."}
• {"endpoint_text":"- Presence, duration, and severity of individual respiratory symptoms (runny/congested nose, sore throat, cough, fever shortness of breath, fatigue/tiredness, sweats/chills, headache, muscle, joint and/or body aches, loss of taste/smell, diarrhoea, other) as: absent, mild, moderate, severe.","definition_or_measurement_approach":"Symptoms recorded and rated by participants (absent/mild/moderate/severe) over study-specified diary days."}
• {"endpoint_text":"- Participant reported overall wellbeing, reported by rating of how well participant feels (scale 0-10)","definition_or_measurement_approach":"Participant self-rating on a 0-10 scale."}
• {"endpoint_text":"- Impact on usual daily activities (work/education, caring for (grand-) children, household activities, sports, social life), as: no, slight, moderate, severe, not applicable.","definition_or_measurement_approach":"Participant-reported impact categories recorded in diary/questionnaires."}
• {"endpoint_text":"- Complications (e.g. hospitalisation, death; all cause, non-elective hospitalisation).","definition_or_measurement_approach":"Clinical events captured through follow-up and healthcare utilisation records."}
• {"endpoint_text":"- Health care utilisation for COVID-19 or COVID-like-illness (GP and hospital visits).","definition_or_measurement_approach":"Recorded GP and hospital visit occurrences related to illness."}
• {"endpoint_text":"- Long-term consequences of COVID-19 or COVID-like-illness (e.g. cough, shortness of breath and/or difficulty breathing, fast heart rate, fatigue, tiredness and/or loss of energy, sleep alterations, loss of smell and/or taste, emotional sensitivity, depression and/or anxiety, concentration problems and/or difficulty thinking, muscle aches and or generalised body pains, diarrhoea and/or stomach pain, other).","definition_or_measurement_approach":"Participant-reported long-term symptoms up to specified follow-up (e.g. up to 6 months)."}
• {"endpoint_text":"- The incidence of COVID-19 and COVID-like-illness in other members of the household (using participants diaries and/or swabbing the symptomatic household member(s)).","definition_or_measurement_approach":"Incidence measured via participant diaries and swab testing of symptomatic household members where specified."}
• {"endpoint_text":"- Exploratory: Emergence of mutations in causative pathogens in index cases and potentially in household members","definition_or_measurement_approach":"Genomic analysis of pathogens from swabs to detect emergence of mutations (exploratory; ISA-specific)."}
• {"endpoint_text":"- Exploratory: Experiences of researchers and network coordinators of setting up the trial in multiple countries, including views on optimising trial delivery, recruitment, and implementation (qualitative study).","definition_or_measurement_approach":"Qualitative interviews / studies with researchers and coordinators."}
• {"endpoint_text":"- Exploratory: Healthcare professionals’ views and experience of taking part in the trial (in the context of a pandemic), the novel trial design, recruiting patients and views on the intervention(s) (qualitative study).","definition_or_measurement_approach":"Qualitative interviews with healthcare professionals."}
• {"endpoint_text":"- Exploratory: Patient views and experiences of taking part in the trial and trial interventions, including how they conceptualise their illness and recovery (qualitative study).","definition_or_measurement_approach":"Qualitative interviews with patients."}
• {"endpoint_text":"- Time to first self-report of feeling recovered from symptoms of COVID-19 or COVID-like-illness (for Phase IIa type evaluation)","definition_or_measurement_approach":"Participant-reported time to feeling recovered (for Phase IIa evaluations as per ISA)."}
• {"endpoint_text":"- Viral clearance at ISA-specified days","definition_or_measurement_approach":"Laboratory-measured viral clearance on ISA-specified days."}
• {"endpoint_text":"- The use of additional antiviral medication (yes/no, name of medication)","definition_or_measurement_approach":"Record of additional antiviral medication use (yes/no) with medication name."}
• {"endpoint_text":"- The use of other prescribed and/or over-the-counter medication for the respiratory infection (antibiotics, antiviral medication, ibuprofen, other pain/fever medication, inhaled medication, intranasal medication, other)","definition_or_measurement_approach":"Recorded concomitant medication use for respiratory infection."}
• {"endpoint_text":"- Sustained recovery (participants’ reported recovery that was maintained until 28 days).","definition_or_measurement_approach":"Participant-reported recovery sustained through Day 28."}
• {"endpoint_text":"- Key secondary outcome: Early sustained recovery (recovery by day 14 sustained until day 28)","definition_or_measurement_approach":"Recovery by Day 14 that is maintained until Day 28 (participant-reported)."}
• {"endpoint_text":"- Overall safety of the IP by reporting (serious) adverse drug reactions","definition_or_measurement_approach":"Safety monitoring via AE/SAE and adverse drug reaction reporting."}
• {"endpoint_text":"- LTX-109 specific: Viral load reduction from Day 0 (baseline) to Day 1, to Day 3 and to Day 5","definition_or_measurement_approach":"Quantitative viral load change from baseline to Day 1, Day 3 and Day 5 for LTX-109 participants."}
• {"endpoint_text":"- LTX-109 specific: Viral clearance at Day 1 and Day 5","definition_or_measurement_approach":"Laboratory-assessed viral clearance at Days 1 and 5 for LTX-109 participants."}
• {"endpoint_text":"- Reduction in viral load from baseline to ISA specified days","definition_or_measurement_approach":"Viral load reduction measured at ISA-specified days (laboratory assays)."}
• {"endpoint_text":"- Tolerability of the IP, via reasons for stopping IP intake.","definition_or_measurement_approach":"Recorded reasons for discontinuation of IP intake as tolerability measure."}

Methods

• Webpage (K2_Recruitment material Webpage) — public-facing recruitment information/webpage
• Printed recruitment materials: Flyer and Poster (K2_Recruitment material Flyer/Poster) — distributed to target audiences (patients visiting primary care sites) in participating countries
• Social media text (documented) — social media channel messaging for recruitment
• Email invites (L2_Other subject information material Email invites) — direct email invitations to potential participants
• Patient Card and recruitment materials in local languages (L2_Other subject information material Patient Card) — distributed at recruiting GP sites
• Recruitment arrangements and informed consent procedure documents (K1_Recruitment and informed consent procedure) — procedures for site-based recruitment via primary care practices

France

Earliest CTIS Part Ii Submission Date

21-02-2024

Latest Decision Or Authorization Date

06-08-2025

Processing Time Days

532

Number Of Sites

1

Number Of Participants

126

Belgium

Earliest CTIS Part Ii Submission Date

25-03-2024

Latest Decision Or Authorization Date

11-09-2025

Processing Time Days

535

Number Of Sites

14

Number Of Participants

183

Poland

Earliest CTIS Part Ii Submission Date

28-03-2024

Latest Decision Or Authorization Date

22-10-2025

Processing Time Days

573

Number Of Sites

6

Number Of Participants

183

Ireland

Earliest CTIS Part Ii Submission Date

27-03-2024

Latest Decision Or Authorization Date

28-08-2025

Processing Time Days

519

Number Of Sites

8

Number Of Participants

147

Germany

Earliest CTIS Part Ii Submission Date

07-03-2024

Latest Decision Or Authorization Date

10-10-2025

Processing Time Days

582

Number Of Sites

3

Number Of Participants

107

Spain

Earliest CTIS Part Ii Submission Date

21-02-2024

Latest Decision Or Authorization Date

21-10-2025

Processing Time Days

608

Number Of Sites

9

Number Of Participants

165

Primary sponsor

Full Name

University Medical Center Utrecht

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"Germany","full_name":"Zentrum für Klinische Studien","duties_or_roles":"Safety management","organisation_type":"Health care"}
• {"country":"Germany","full_name":"Wurzburg University Hospital","duties_or_roles":"National Coordinating Team","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United Kingdom","full_name":"University Of Oxford","duties_or_roles":"National Coordinating Team","organisation_type":"Educational Institution"}
• {"country":"Georgia","full_name":"Arner ScienceManagement","duties_or_roles":"National Coordinating Team","organisation_type":"Health care"}
• {"country":"Spain","full_name":"Fundació Institut Universitari per a la Investigació en la Atenció Primària Jordi Gol i Gurina","duties_or_roles":"National Coordinating Team","organisation_type":"Health care"}
• {"country":"Poland","full_name":"Medical University Of Bialystok","duties_or_roles":"National Coordinating Team","organisation_type":"Educational Institution"}
• {"country":"Ireland","full_name":"University College Dublin","duties_or_roles":"National Coordinating Team","organisation_type":"Educational Institution"}
• {"country":"France","full_name":"Centre Hospitalier Et Universitaire De Limoges","duties_or_roles":"National Coordinating Team","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Belgium","full_name":"University Of Antwerp","duties_or_roles":"National Coordinating Team and central lab","organisation_type":"Educational Institution"}
• {"country":"Netherlands","full_name":"ALEA Clinical Services","duties_or_roles":"unspecified (sponsor duty code 3)","organisation_type":"Health care"}
• {"country":"Germany","full_name":"Myonex GmbH","duties_or_roles":"sponsor duty code 14","organisation_type":"Pharmaceutical company"}