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Antiviral Nasal Sprays — Human Clinical Trials

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Trials by Ingredient (n = 51)

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Favors treatmentFavors controlMixedNo difference (null)Inconclusive / not assessableResult unknown

Trials by Year (n = 51)

Trials

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Showing 51 of 51 trials

Tolerance of one‐month intranasal interferon
Scott GM et al.. Journal of Medical Virology 17(2) 99-106. (1985)
leukocyte/lymphoblastoid interferonNasal spray
RCTN = 68
Discontinuation due to upper respiratory symptoms (definite cold or reaction) during treatment
InconclusiveRoB: Some Concerns
Azelastine Nasal Spray for Prevention of SARS-CoV-2 Infections
Thorsten Lehr et al.. JAMA Internal Medicine 185(11) 1309. (2025)
azelastineNasal spray
RCTN = 450
PCR-confirmed SARS-CoV-2 infection (primary endpoint)— Odds ratio 0.31 (0.11–0.87), p=0.02
Favors treatmentRoB: Some Concerns
Nasal spray of an IgM-like ACE2 fusion protein HH-120 prevents SARS-CoV-2 infection: Two investigator-initiated postexposure prophylaxis trials
Song et al.. Journal of Medical Virology. (2023)
igm-like ace2 fusion protein (hh-120)Nasal spray
RCT
SARS-CoV-2 infection rate (NS01 trial, continuous close contact)
No differenceRoB: Some Concerns
Clinical evaluation of prophylactic intranasal 1-phenyl-3-(4-phenyl-2-thiazolyl) guanidine (CL 88,277) medication against rhinovirus 44 challenge
Yasushi Togo et al.. Medical Microbiology and Immunology 163(1) 37-44. (1977)
1-phenyl-3-(4-phenyl-2-thiazolyl) guanidine (cl 88,277)Nasal spray
Human-ChallengeN = 20
Rhinovirus illness incidence (any illness)
No differenceRoB: Some Concerns
Intranasal interferon (rIFN-αA, Ro 22-8181) for contact prophylaxis against common cold: A randomized, double-blind and placebo-controlled field study
Christian Herzog et al.. Antiviral Research 6(3) 171-176. (1986)
interferon alpha (unspecified subtype)Nasal spray
RCTN = 587
Development of common cold in initially symptom-free contact persons (infection rate)
No differenceRoB: Some Concerns
The efficacy of intranasal interferonα-2a in respiratory syncytial virus infection in volunteers
Paul G. Higgins et al.. Antiviral Research 14(1) 3-10. (1990)
interferon alpha-2aNasal spray
Human-Challenge
Incidence of colds (prophylactic trial)
MixedRoB: Some Concerns
Failure to demonstrate synergy between interferon-α and a synthetic antiviral, enviroxime, in rhinovirus infections in volunteers
Peter G. Higgins et al.. Antiviral Research 10(1-3) 141-149. (1988)
interferon alpha (unspecified subtype)Nasal spray
Human-ChallengeN = 57
Clinically significant cold (clinical diagnosis)
No differenceRoB: Some Concerns
An effective dosage regimen for prophylaxis against rhinovirus infection by intranasal administration of HuIFN-α2
Phillpotts RJ et al.. Antiviral Research 3(2) 121-136. (1983)
interferon alpha (unspecified subtype)Nasal spray
Human-Challenge
Clinically diagnosed colds (mild or worse)
No differenceRoB: Some Concerns
A randomized controlled trial of low-dose recombinant human interferons α-2b nasal spray to prevent acute viral respiratory infections in military recruits
LuLu Gao et al.. Vaccine 28(28) 4445-4451. (2010)
interferon alpha-2bNasal spray
RCTN = 1,449
Influenza A virus infection rate (serum IgM seroconversion) - PP analysis— Risk ratio 0.24 (0.15–0.36), p=0.00
Favors treatmentRoB: Some Concerns
A study of intranasally administered interferon A (rIFN-α2A) for the seasonal prophylaxis of natural viral infections of the upper respiratory tract in healthy volunteers
Tannock GA et al.. Epidemiology and Infection 101(3) 611-621. (1988)
interferon alpha-2aNasal spray
RCTN = 412
Laboratory-documented viral infection (virus isolation and/or antibody response)— Risk ratio 1.11 (0.77–1.60)
No differenceRoB: Some Concerns
Post-exposure prophylaxis with SA58 (anti-SARS-CoV-2 monoclonal antibody) nasal spray for prevention of symptomatic COVID-19 in healthy adult workers: a randomized single-blind placebo-controlled study
Song et al.. Emerging Microbes & Infections. (2023)
sa58 (anti-sars-cov-2 monoclonal antibody)Nasal spray
RCTN = 1,222
Laboratory-confirmed symptomatic COVID-19— Rate ratio 0.19 (0.08–0.48)
Favors treatmentRoB: Some Concerns
Inhibition of Rhinovirus Replication In Vitro and In Vivo by Acid‐Buffered Saline
James E. Gern et al.. The Journal of Infectious Diseases 195(8) 1137-1143. (2007)
citrate/phosphate bufferNasal spray
Human-ChallengeN = 44
Clinical cold incidence (Jackson criteria: confirmed infection + symptom score ≥6 + rhinorrhea ≥3 days or subject impression of cold)
Favors treatmentRoB: Some Concerns
1524 Design and Implementation Of ICE-COVID, A Double-Blind Randomised Placebo-Controlled Trial on The Efficacy of Iota-Carrageenan Nasal and Throat Spray for Covid-19 Prophylaxis
Jia Yin Lim et al.. British Journal of Surgery 108(Supplement_6). (2021)
iota-carrageenanNasal spray
RCTN = 480
Acquisition of COVID-19 infection
InconclusiveRoB: Some Concerns
Interferon-β ser As Prophylaxis Against Experimental Rhinovirus Infection in Volunteers
Higgins PG et al.. Journal of Interferon Research 6(2) 153-159. (1986)
interferon beta serineNasal spray
Human-ChallengeN = 64
Clinically significant colds
No differenceRoB: Some Concerns
Recombinant Human Interferon-γ as Prophylaxis Against Rhinovirus Colds in Volunteers
Paul G. Higgins et al.. Journal of Interferon Research 8(5) 591-596. (1988)
interferon gammaNasal spray
Human-ChallengeN = 43
Significant clinical illness (cold)
Favors controlRoB: Some Concerns
Intranasal Lymphoblastoid Interferon ("Well fer on") Prophylaxis Against Rhinovirus and Influenza Virus in Volunteers
R.J. Phillpotts et al.. Journal of Interferon Research 4(4) 535-541. (1984)
leukocyte/lymphoblastoid interferonNasal spray
Human-ChallengeN = 96
Clinically significant cold (mild or worse) — Trial 1 (rhinovirus)
MixedRoB: Some Concerns
Interferon-α Nasal Spray Prophylaxis Reduces COVID-19 in Cancer Patients: A Randomized, Double-Blinded, Placebo-Controlled Trial
Michelle K. Yong et al.. Clinical Infectious Diseases 82(2) e208-e216. (2026)
interferon alpha (unspecified subtype)Nasal spray
RCTN = 433
Incidence of COVID-19 infection within 90 days (ITT)— Risk ratio 0.60 (0.33–0.97)
MixedRoB: Low
Efficacy and Tolerance of Intranasally Applied Recombinant Leukocyte A Interferon in Normal Volunteers
Samo TC et al.. Journal of Infectious Diseases 148(3) 535-542. (1983)
leukocyte/lymphoblastoid interferonNasal spray
Human-ChallengeN = 27
Frequency of illness (proportion of treated volunteers ill)
Favors treatmentRoB: Some Concerns
Effect of CP20,961, an Interferon Inducer, on Upper Respiratory Tract Infections Due to Rhinovirus Type 21 in Volunteers
Waldman RH et al.. Journal of Infectious Diseases 138(4) 531-535. (1978)
cp-20,961 (avridine)Nasal spray
Human-ChallengeN = 60
Clinical illness rate
No differenceRoB: Some Concerns
Intranasal Interferon- 2, Treatment of Experimental Rhinoviral Colds
Hayden FG et al.. Journal of Infectious Diseases 150(2) 174-180. (1984)
interferon alpha (unspecified subtype)Nasal spray
Human-ChallengeN = 52
Rhinovirus infection rate (viral isolation and/or seroconversion)
No differenceRoB: Some Concerns
Prevention of Experimental Coronavirus Colds with Intranasal  -2b Interferon
Turner RB et al.. Journal of Infectious Diseases 154(3) 443-447. (1986)
interferon alpha-2bNasal spray
Human-ChallengeN = 56
Met symptom criteria for a cold
Favors treatmentRoB: Some Concerns
Intranasally Applied Recombinant Leukocyte A Interferon in Normal Volunteers. II. Determination of Minimal Effective and Tolerable Dose
Samo Tc et al.. Journal of Infectious Diseases 150(2) 181-188. (1984)
interferon alpha (unspecified subtype)Nasal spray
Human-ChallengeN = 63
Frequency of illness (proportion of treated volunteers who became ill)
Favors treatmentRoB: Some Concerns
Intranasal Interferon- 2 Prophylaxis of Natural Respiratory Virus Infection
Douglas RM et al.. Journal of Infectious Diseases 151(4) 731-736. (1985)
interferon alpha (unspecified subtype)Nasal spray
RCTN = 413
Number of volunteers experiencing respiratory episodes (medication phase)
No differenceRoB: Some Concerns
Influenza b in households: virus shedding without symptoms or antibody response
HJORDIS M. FOY et al.. American Journal of Epidemiology 126(3) 506-515. (1987)
interferon alpha (unspecified subtype)Nasal spray
RCTN = 53
Influenza B infection (virus isolation or significant antibody titer rise) in households
No differenceRoB: Some Concerns
Intranasal Interferon- 2b for Seasonal Prophylaxis of Respiratory Infection
Monto AS et al.. Journal of Infectious Diseases 154(1) 128-133. (1986)
interferon alpha-2bNasal spray
RCTN = 550
Rhinovirus infection during prophylaxis (twice-daily schedule)— Risk ratio 0.24, p=0.01
Favors treatmentRoB: Some Concerns
Intranasal interferon as protection against experimental respiratory coronavirus infection in volunteers
Higgins PG et al.. Antimicrobial Agents and Chemotherapy 24(5) 713-715. (1983)
interferon alpha (unspecified subtype)Nasal spray
Human-ChallengeN = 83
Clinically diagnosed colds (mild or worse)
Favors treatmentRoB: Some Concerns
Intranasal interferon-alpha 2 for prevention of natural rhinovirus colds
Farr BM et al.. Antimicrobial Agents and Chemotherapy 26(1) 31-34. (1984)
interferon alpha (unspecified subtype)Nasal spray
RCTN = 304
Rhinovirus-documented respiratory illness (culture-confirmed rhinovirus infection during treatment)
Favors treatmentRoB: Some Concerns
Lack of Effect of an Interferon Inducer, N,N -Dihexadecyl- m -Xylylenediamine, on Rhinovirus Challenge in Humans
Douglas RG Jr et al.. Antimicrobial Agents and Chemotherapy 15(2) 269-272. (1979)
n,n-dihexadecyl-m-xylylenediamine (cp-28,888-27)Nasal spray
Human-ChallengeN = 62
Virus isolation from nasal washes
No differenceRoB: Some Concerns
Effect of Induced Interferon in Experimental Rhinovirus Infections in Volunteers
Douglas RG Jr et al.. Infection and Immunity 9(3) 506-510. (1974)
cp-20,961 (avridine)Nasal spray
Human-ChallengeN = 29
Clinical illness (number becoming ill)
No differenceRoB: Some Concerns
Safety and efficacy of intranasal pirodavir (R77975) in experimental rhinovirus infection
Frederick G. Hayden et al.. Antimicrobial Agents and Chemotherapy 36(4) 727-732. (1992)
pirodavirNasal spray
Human-ChallengeN = 132
Infection rate (virus shedding or seroconversion) — Prophylaxis Study 1 (6x/day)
Favors treatmentRoB: Some Concerns
Prophylactic intranasal alpha 2 interferon and viral exacerbations of chronic respiratory disease.
Wiselka MJ et al.. Thorax 46(10) 706-711. (1991)
interferon alpha (unspecified subtype)Nasal spray
RCTN = 123
Lower respiratory tract infection
No differenceRoB: Some Concerns
Phase II, Randomized, Double-Blind, Placebo-Controlled Studies of Ruprintrivir Nasal Spray 2-Percent Suspension for Prevention and Treatment of Experimentally Induced Rhinovirus Colds in Healthy Volunteers
Frederick G. Hayden et al.. Antimicrobial Agents and Chemotherapy 47(12) 3907-3916. (2003)
ruprintrivirNasal spray
Human-ChallengeN = 202
Proportion of subjects with positive viral culture (prophylaxis 5x/day)
Favors treatmentRoB: Some Concerns
Safety and Efficacy of Once Daily Intranasal Zanamivir in Preventing Experimental Human Influenza a Infection
David P. Calfee et al.. Antiviral Therapy 4(3) 143-149. (1999)
zanamivirNasal spray
Human-ChallengeN = 47
Viral shedding (isolation of challenge virus from nasal blow or throat gargle)
MixedRoB: Some Concerns
Evaluation of Intranasal TLR2/6 agonist INNA-051: Safety, Tolerability and Proof of Pharmacology
Francesca A. Mercuri et al.. ERJ Open Research 10(6) 00199-2024. (2024)
inna-051Nasal spray
Human-ChallengeN = 119
Laboratory-confirmed infection incidence (two quantifiable qRT-PCR samples on 2 consecutive days) — ITT population
No differenceRoB: Some Concerns
Efficacy of a Nasal Spray Containing Iota-Carrageenan in the Postexposure Prophylaxis of COVID-19 in Hospital Personnel Dedicated to Patients Care with COVID-19 Disease
Juan Manuel Figueroa et al.. International Journal of General Medicine Volume 14 6277-6286. (2021)
iota-carrageenanNasal spray
RCTN = 400
RT-PCR confirmed symptomatic COVID-19— Odds ratio 0.19 (0.05–0.77), p=0.03
Favors treatmentRoB: Some Concerns
A field trial of recombinant human interferon alpha-2b for nasal spray to prevent SARS and other respiratory viral infections
Yu DX et al.. Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of ex 19(3) 216-9. (2005)
(Extracted from abstract only)
interferon alpha-2bNasal spray
RCTN = 14,391
SARS IgG antibody positive rate
No differenceRoB: Some Concerns
Prevention from naturally acquired viral respiratory infection by interferon nasal spray
Saito H et al.. Rhinology 23(4) 291-5. (1985)
(Extracted from abstract only)
interferon alpha (unspecified subtype)Nasal spray
RCTN = 73
Subjects without elevated antibody titers and without symptoms
No differenceRoB: High
The Limited Effect of Nasal Interferon Induced by Rhinovirus and a Topical Chemical Inducer on the Course of Infection
Gatmaitan BC et al.. Journal of Infectious Diseases 127(4) 401-407. (1973)
cp-20,961 (avridine)Nasal spray
Human-ChallengeN = 38
Clinical illness (common cold)
No differenceRoB: Some Concerns
Purified interferon as protection against rhinovirus infection.
Scott GM et al.. BMJ 284(6332) 1822-1825. (1982)
leukocyte/lymphoblastoid interferonNasal spray
Human-Challenge
Incidence of colds
Favors treatmentRoB: Some Concerns
Short-Term Treatment with Zanamivir to Prevent Influenza: Results of a Placebo-Controlled Study
Kaiser L. et al.. Clinical Infectious Diseases 30(3) 587-589. (2000)
(Extracted from abstract only)
zanamivirNasal spray
RCTN = 575
Symptomatic influenza during 5 days of prophylaxis— Odds ratio 0.90 (0.30–2.72), p=0.85
No differenceRoB: Some Concerns
Prophylactic efficacy and tolerance of low-dose intranasal interferon-alpha2 in natural respiratory viral infections
Frederick G. Hayden et al.. Antiviral Research 5(2) 111-116. (1985)
interferon alpha (unspecified subtype)Nasal spray
RCTN = 287
Respiratory illness episodes
Favors controlRoB: Some Concerns
Human monoclonal antibody F61 nasal spray effectively protected high-risk populations from SARS-CoV-2 variants during the COVID-19 pandemic from late 2022 to early 2023 in China
Ying Liu et al.. Emerging Microbes & Infections 13(1) 2284297. (2024)
human monoclonal antibody f61Nasal spray
RCTN = 2,008
Cumulative SARS-CoV-2 infection rate at Day 7 (one-dose cohort)
Favors treatmentRoB: Some Concerns
Intranasal chalcone, Ro 09–0410, as prophylaxis against rhinovirus infection in human volunteers
Al-Nakib W. et al.. Journal of Antimicrobial Chemotherapy 20(6) 887-892. (1987)
chalcone ro 09-0410Nasal spray
Human-ChallengeN = 50
Significant colds (clinical illness)
No differenceRoB: Some Concerns
PROphylaxis for paTiEnts at risk of COVID-19 infecTion (PROTECT-V)
Toby J. L. Humphrey et al.. Trials 24(1) 185. (2023)
(Extracted from abstract only)
niclosamideNasal spray
RCT
Symptomatic SARS-CoV-2 infection
InconclusiveRoB: Some Concerns
Prophylactic activity of intranasal enviroxime against experimentally induced rhinovirus type 39 infection
Hayden FG et al.. Antimicrobial Agents and Chemotherapy 21(6) 892-897. (1982)
enviroximeNasal spray
Human-ChallengeN = 40
Total infection rate (virus isolation or seroconversion)
No differenceRoB: Some Concerns
Therapeutic activity of enviroxime against rhinovirus infection in volunteers
Phillpotts RJ et al.. Antimicrobial Agents and Chemotherapy 23(5) 671-675. (1983)
enviroximeNasal spray
Human-ChallengeN = 55
Clinically diagnosed cold (mild or worse) — all HRV9-challenged volunteers
No differenceRoB: Some Concerns
Suppression of colds in human volunteers challenged with rhinovirus by a new synthetic drug (R61837)
al-Nakib W. et al.. Antimicrobial Agents and Chemotherapy 33(4) 522-525. (1989)
r61837Nasal spray
Human-Challenge
Number of significant colds (Trial 1: First Prophylactic)
No differenceRoB: Some Concerns
Prophylaxis for renal patients at risk of COVID-19 infection: results from the intranasal niclosamide randomised, double blinded, placebo controlled arm of the PROTECT-V platform trial
Toby J. L. Humphrey et al.. BMC Infectious Diseases 25(1) 204. (2025)
niclosamideNasal spray
RCTN = 1,651
Confirmed symptomatic COVID-19 infection during trial treatment— Hazard ratio 1.02 (0.79–1.32)
No differenceRoB: Some Concerns
Topical enviroxime against rhinovirus infection
Levandowski RA et al.. Antimicrobial Agents and Chemotherapy 22(6) 1004-1007. (1982)
enviroximeNasal spray
Human-ChallengeN = 101
RV4-specific cold (clinical cold meeting case definition)
No differenceRoB: Some Concerns
Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19
Zaki F. Aref et al.. International Journal of Nanomedicine Volume 16 4063-4072. (2021)
ivermectinNasal spray
RCTN = 114
PCR negative conversion (2 consecutive negative nasopharyngeal swabs)
Favors treatmentRoB: High
Safety and efficacy of the neuraminidase inhibitor GG167 in experimental human influenza.
Hayden FG et al.. JAMA 275(4) 295-9. (1996)
(Extracted from abstract only)
4-guanidino-neu5ac2en (gg167)Nasal spray
Human-ChallengeN = 166
Laboratory-confirmed infection (viral shedding and/or seroconversion) — prophylaxis— Risk difference -0.82, p=0.01
Favors treatmentRoB: Some Concerns