Clinical trial for the treatment of COVID-19 and COVID-like illness in primary care

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Medical Center Utrecht

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

3 Oct 2024 → ongoing

Decision date (initial)

2024-04-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

European Union

External identifiers

EU CT number

2022-501707-27-01

ISRCTN

ISRCTN55471843

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

The primary objective(s) of this platform study will be phase dependent.

To assess the efficacy of the study IP versus control (Usual Care) or versus a comparator (placebo, or comparator IP) on:
- Time to first self-report of feeling recovered from symptoms of COVID-19 or COVID-like-illness (for Phase IIb/III type evaluation, as specified in the relevant intervention specific appendix).
- Viral clearance and potentially viral load and/or impact on biomarkers, for example on illness severity or immunological response (for Phase IIa type evaluation as specified in the relevant intervention specific appendix).

For ISA A/B/C the primary objective is as per master protocol.

For ISA D the primary objective will be:
- 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).

Secondary objectives 24

1. Sustained recovery (participants’ reported recovery that was maintained until 28 days)
2. Presence, duration and severity of individual respiratory symptoms
3. Participant reported overall wellbeing
4. Evaluation of overall safety of the IP by monitoring of (serious) AEs and (serious) adverse drug reactions.
5. The occurrence of the complications (hospitalisation, death; all-cause, non-elective hospitalisation will be assessed)
6. Impact on usual daily activities
7. Health care utilisation (e.g. GP and hospital visits)
8. Long-term (up to 6 months) consequences of COVID-19 or COVID-like-illness
9. The incidence of COVID-19 and COVID-like-illness in other members of the household
10. Exploratory: The emergence of mutations in causative pathogens in index cases and potentially in household members (where specified in the relevant intervention specific appendix).
11. Exploratory: To assess the experiences of researchers/ network coordinators of setting up the trial in multiple countries, including views on optimising trial delivery, recruitment, and implementation (qualitative study).
12. Exploratory: To assess healthcare professionals’ views and experience of taking part in the trial (in the context of an epidemic or pandemic), the novel trial design, recruiting patients and views on the intervention(s) (qualitative study).
13. Exploratory: To assess patient views and experiences of taking part in the trial and trial interventions, including intervention adherence (qualitative study).
14. Time to first self-report of feeling recovered from symptoms of COVID-19 or COVID-like-illness (for Phase IIa type evaluation)
15. Viral clearance (for Phase IIb and III type evaluation)
16. The use of additional antiviral medication
17. The use of other prescribed and/or over-the-counter medication for the respiratory infection
18. The key secondary outcome will be Early sustained recovery which is defined recovery by day 14, sustained until day 28
19. Time to first self-report of return to usual daily activity
20. LTX-109 specific: Viral load reduction from baseline (Day 0) to Day 1, to Day 3 and to Day 5
21. LTX-109 specific: Viral clearance at Day 1 and Day 5
22. Reduction in viral load
23. Tolerability of the IP
24. IP intake adherence

Conditions and MedDRA coding

COVID-like-illness

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 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
2. LTX-109 specific: Inclusion within 3 days since onset of respiratory symptoms
3. 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).
4. Judged by recruiting medically qualified clinician or delegate that the illness is due to a respiratory infection
5. Onset of symptoms less than x days (x will be specified in the ISA
6. Willing and able to give informed consent for participation in the study
7. Willing and able to comply with all trial procedures (including availability of freezer at participant’s home to store self-collected swabs).
8. 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
9. NONS and SN Spray specific: Onset of symptoms within 3 days
10. 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.
11. NONS and SN Spray specific: For women of child-bearing potential, a negative urine pregnancy test.

Exclusion criteria 13

1. Requiring admission to the hospital on the day of inclusion.
2. NONS and SN Spray specific: Current of history of moderate to severe epistaxis or hereditary hemorrhagic telangiectasia
3. NONS and SN Spray specific: History of cerebral spinal fluid leaks via the sinuses/nose
4. Any personnel involved in the study
5. NONS and SN Spray specific: Recent nasal fracture, nasal tumors, nasal masses, meningoencephalocele, and/or nasal surgery within the previous 2 weeks
6. LTX-109 specific: Any known nasal anatomical anomalies
7. 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.
8. Known allergies or hypersensitivities to any of the components used in the formulation of the IP, or the control product.
9. 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.
10. Any planned major surgery in the next 28 days.
11. Currently participating in a trial of a pharmacological treatment.
12. NONS and SN Spray specific: Known to be currently pregnant or breastfeeding
13. NONS and SN Spray specific: Known glucose-6-phosphate-dehydrogenase (G6PD) deficiency.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Time to first self-report of feeling recovered from symptoms related to COVID-19 or COVID-like-illness.
2. 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
3. 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)

Secondary endpoints 23

1. Time to first self-report of return to usual daily activity.
2. 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.
3. Participant reported overall wellbeing, reported by rating of how well participant feels (scale 0-10)
4. Impact on usual daily activities (work/education, caring for (grand-) children, household activities, sports, social life), as: no, slight, moderate, severe, not applicable.
5. Complications (e.g. hospitalisation, death; all cause, non-elective hospitalisation).
6. Health care utilisation for COVID-19 or COVID-like-illness (GP and hospital visits).
7. 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).
8. 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)).
9. Exploratory: Emergence of mutations in causative pathogens in index cases and potentially in household members
10. 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).
11. 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).
12. Exploratory: Patient views and experiences of taking part in the trial and trial interventions, including how they conceptualise their illness and recovery (qualitative study).
13. Time to first self-report of feeling recovered from symptoms of COVID-19 or COVID-like-illness (for Phase IIa type evaluation)
14. Viral clearance at ISA-specified days
15. The use of additional antiviral medication (yes/no, name of medication)
16. 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)
17. Sustained recovery (participants’ reported recovery that was maintained until 28 days).
18. Key secondary outcome: Early sustained recovery (recovery by day 14 sustained until day 28)
19. Overall safety of the IP by reporting (serious) adverse drug reactions
20. LTX-109 specific: Viral load reduction from Day 0 (baseline) to Day 1, to Day 3 and to Day 5
21. LTX-109 specific: Viral clearance at Day 1 and Day 5
22. Reduction in viral load from baseline to ISA specified days
23. Tolerability of the IP, via reasons for stopping IP intake.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Medical Center Utrecht

Sponsor organisation

University Medical Center Utrecht

Address

Heidelberglaan 100

City

Utrecht

Postcode

3584 CX

Country

Netherlands

Scientific contact point

Organisation

University Medical Center Utrecht

Contact name

A.W. van der Velden

Public contact point

Organisation

University Medical Center Utrecht

Contact name

A.W. van der Velden

Third parties 11

Locations

6 EU/EEA countries · 41 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 192 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications