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CompletedNCT03290248Updated Nov 25, 2022Results posted

Study to Assess the Safety, Tolerability, and Preliminary Efficacy of B244 in Healthy Volunteers and Subjects With Seasonal Allergic Rhinitis

A Phase 1/2 interventional study of B244 suspension and Vehicle in Allergic Rhinitis, Allergic Rhinitis Due to Grass Pollen and Healthy Volunteers, sponsored by AOBiome LLC. Completed at 2 sites in 2 countries. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-11-25.

Sponsored by AOBiome LLC · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
71
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

This is a Prospective, Controlled, Double Blinded, Single Center, Randomized, 3 Arm, Parallel Assignment, Phase 1b/2a Study to assess the safety, tolerability, and preliminary efficacy of B244 delivered as an intranasal spray in healthy volunteers and subjects with seasonal allergic rhinitis.

Read the detailed description

This is a Prospective, Controlled, Double Blinded, Single Center, Randomized, 3 Arm, Parallel Assignment, Phase 1b/2a Study to assess the safety, tolerability, and preliminary efficacy of B244 delivered as an intranasal spray in healthy volunteers and subjects with seasonal allergic rhinitis. This will be a 2-part study. In Part 1, safety and tolerability will be evaluated during 14 days of study treatment twice-a-day followed by 4 weeks of follow-up in healthy volunteers. In Part 2, preliminary efficacy will be evaluated in subjects with a history of seasonal allergic rhinitis outside of the local pollen season.

For Part 1 (safety and tolerability evaluation in healthy volunteers) we will enroll 24 subjects. Safety and tolerability will be assessed by reporting of AEs, physical examination and vital signs (blood pressure, heart rate, respiratory rate) during 14 days of treatment and up to 28 days of follow-up.

An internal safety committee meeting will review the 2 week Part 1 safety data and, if there are no safety concerns, the study will proceed to Part 2 to evaluate preliminary efficacy in subjects with a history of seasonal allergic rhinitis (SAR)

For Part 2 (preliminary efficacy evaluation in subjects with a history of SAR to ragweed pollen) will enroll 42 subjects. Safety and tolerability will be assessed in subjects with allergic rhinitis by reporting of AEs, physical examination and vital signs (blood pressure, heart rate, respiratory rate) during 14 days of treatment.

For Part 2, study will be paused for safety review using the same stopping criteria as in Part 1.

Rescue medications will not be allowed during the study.

02

Conditions studied

  • Allergic Rhinitis
  • Allergic Rhinitis Due to Grass Pollen
  • Healthy Volunteers
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Males and Females, 18 to 65 years of age (committed to consistent use of an acceptable method of birth control as described in Section 10).
  • In good general health as determined by a thorough medical history and physical examination, and vital signs.
  • Nonsmoker or ex-smoker (stopped >1 year prior to study entry).
  • Subjects willing and able to provide written informed consent.
  • Is willing and able to comply with the requirements of the protocol and must be available for the full duration of the study.
  • For Part 1, subjects asymptomatic from any seasonal or perennial allergens.
  • For Part 1, elevated systolic blood pressure greater than 120 but less than 160 and never been on antihypertensive medications or have been off any hypertensive treatment for a period of 12 weeks or longer.
  • For Part 2, subjects with a well-documented history of seasonal allergic rhinitis (specifically ragweed pollen) with documentation of sensitivity by positive skin testing and/or IgE testing to the relevant allergens 12 months prior to enrollment that correlate with clinical history.
  • For Part 2, a ragweed positive skin prick test with a wheal diameter at least 5 mm larger than the negative control and/or a ragweed specific IgE greater or equal to 0.7 kU/L.
  • For Part 2, subjects with confounding allergies, or sensitization to cat epithelia, dog epithelia, Dermatophagoides farinae, or Dermatophagoides pteronyssinus or prevalent and relevant seasonal allergens as per the skin prick test may be included if sensitization is not clinically relevant (ie. subject is non-symptomatic and/or can avoid the allergen during the study) at the discretion of the Investigator.
  • For Part 2, subjects with a baseline TNSS ≤ 3/12 at Visit 3 and a minimum qualifying TNSS score of a change of 6/12 from their baseline score after NAC #1 on at least 2 diary cards.
  • For Part 2, subjects' average post diluents nasal congestion score must be \< 1 at admission for each study visit.

Exclusion criteria

Exclusion Criteria:

  • Pregnancy or breast-feeding
  • Female of childbearing potential not using adequate contraceptive measures.
  • Smoking within the past year or during the protocol.
  • Systemic corticosteroid or other immunosuppressive medications use in the previous three months or during the protocol.*
  • Intranasal corticosteroid use in the previous month or during the protocol.*
  • Intranasal antihistamine or cromolyn use in the previous week or during the study.*
  • Allergen immunotherapy during previous 12 months or during the protocol.*
  • Omalizumab use in previous 12 months or during the protocol.*
  • Systemic antihistamine or leukotriene modifying medication use in the previous week or during the protocol.*
  • Use of antibiotics, NSAIDS, antihypertensives, beta-blockers, photosensitizing medications, or vitamin D supplements during study.
  • Use of any intranasally administered over-the-counter product or nasal irrigation (e.g., neti pot) during study.
  • Inability to give informed consent.
  • Persistent asthma or any medical condition that in the opinion of the investigator may compromise the subject's ability to safely participate in the study.
  • Subjects with any significant clinical abnormalities which may interfere with study participation.
  • Prior use of AO+ Mist.
  • Subjects with immunodeficiencies, nasal lesions, nasal polyps, or sinus infections.
  • Use of an investigational drug within 30 days before screening Visit 1. * Exclusionary criterion due to 1) medication use as marker of persistent comorbid allergic or inflammatory condition that may increase subject risk with study participation, 2) potential of medication to interfere with study outcome measures or results.
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
71 participants (actual)

Study arms

  • Placebo comparator
    Vehicle

    Intranasal application: 1 pump (140ul) per nostril BID for 14 days

    Biological: Vehicle

  • Active comparator
    B 244 1x (low dose)

    Intranasal application: 1 pump (140ul) per nostril BID for 14 days

    Biological: B244 suspension

  • Active comparator
    B244 4x (mid dose)

    Intranasal application: 1 pump (140ul) per nostril BID for 14 days

    Biological: B244 suspension

Interventions

  • BiologicalB244 suspension

    B244 suspension in 30ml/bottle

  • BiologicalVehicle

    Vehicle, 30ml/bottle

05

What researchers measure

Primary outcomes

  1. Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

    Safety and tolerability endpoints will consist of all treatment-related adverse events reporting during the study duration for subjects only from Part 1 of the study.

    Time frame: Baseline to Day 28

Secondary outcomes

  1. Change in Total Nasal Symptom Score (TNSS) After Prophylaxis Treatment

    Total Nasal Symptom Score (TNSS) is the sum of sub-scores for each of nasal congestion, sneezing, nasal itching, and rhinorrhea at each time point, using a four point scale (0-3; 0 = none; 1 = mild; 2 = moderate; 3 = severe), where 0 indicates no symptoms, a score of 1 for mild symptoms that are easily tolerated, 2 for awareness of symptoms which are bothersome but tolerable and 3 is reserved for severe symptoms that are hard to tolerate and interfere with daily activity. TNSS is calculated by adding the sub-score for each of the symptoms to a total out of 12. For TNSS and Area Under the Curve (AUC) analyses, an Analysis of Covariance with treatment and site as factors and Visit 3 (or Visit 2) value as a covariate was used to test for treatment effect at Visit 4. Observed AUC (0-2 Hours) was defined as TNSS from 0 to 120 minutes post Nasal Allergen Challenge (NAC). The Pre-NAC Adjusted AUC (0-2 Hours) was defined as the observed value minus the 0 minutes prior NAC value.

    Time frame: Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.

  2. Subjective Nasal Symptom Scores of Nasal Congestion After Prophylaxis Treatment

    All measurements were taken 120 minutes Post-Nasal Allergen Challenge (Post-NAC) at Visit 4 and compared to Baseline Visit 3. Visit 3 was considered Baseline. Visit 2 was considered an alternate Baseline. Nasal congestion was categorized as None, Mild, Moderate, or Severe.

    Time frame: Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.

  3. Subjective Nasal Symptom Scores of Rhinorrhea After Prophylaxis Treatment

    All measurements were taken 120 minutes Post-Nasal Allergen Challenge (Post-NAC) at Visit 4 and compared to Baseline Visit 3. Visit 3 was considered Baseline. Visit 2 was considered an alternate Baseline. Rhinorrhea was categorized as None, Mild, Moderate, or Severe.

    Time frame: Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.

  4. Subjective Nasal Symptom Scores of Nasal Itching After Prophylaxis Treatment

    All measurements were taken 120 minutes Post-Nasal Allergen Challenge (Post-NAC) at Visit 4 and compared to Baseline Visit 3. Visit 3 was considered Baseline. Visit 2 was considered an alternate Baseline. Nasal itching was categorized as None, Mild, Moderate, or Severe.

    Time frame: Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.

  5. Subjective Nasal Symptom Scores of Sneezing After Prophylaxis Treatment

    All measurements were taken 120 minutes Post-Nasal Allergen Challenge (Post-NAC) at Visit 4 and compared to Baseline Visit 3. Visit 3 was considered Baseline. Visit 2 was considered an alternate Baseline. Sneezing was categorized as None, Mild, Moderate, or Severe.

    Time frame: Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.

  6. Nasal Symptom-free Response Rate in Nasal Congestion Scores After Prophylaxis Treatment

    Nasal symptom free response rate was assessed 120 minutes Post-Nasal Allergen Challenge (Post-NAC) to be scored as Yes or No to nasal congestion at Visit 4 (yes indicates subject is free from nasal congestion symptom and no indicates subject still has nasal itching symptom). Visit 3 was considered Baseline. Visit 2 was considered an alternate Baseline.

    Time frame: Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.

  7. Nasal Symptom-free Response Rate in Rhinorrhea Scores After Prophylaxis Treatment

    Nasal symptom free response rate was assessed 120 minutes Post-Nasal Allergen Challenge (Post-NAC) to be scored as Yes or No to rhinorrhea at Visit 4 (yes indicates subject is free from rhinorrhea symptom and no indicates subject still has nasal itching symptom). Visit 3 was considered Baseline. Visit 2 was considered an alternate Baseline.

    Time frame: Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.

  8. Nasal Symptom-free Response Rate in Nasal Itching Scores After Prophylaxis Treatment

    Nasal symptom free response rate was assessed 120 minutes Post-Nasal Allergen Challenge (Post-NAC) to be scored as Yes or No to nasal itching at Visit 4 (yes indicates subject is free from nasal itching symptom and no indicates subject still has nasal itching symptom). Visit 3 was considered Baseline. Visit 2 was considered an alternate Baseline.

    Time frame: Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.

  9. Nasal Symptom-free Response Rate in Sneezing Scores After Prophylaxis Treatment

    Nasal symptom free response rate was assessed 120 minutes Post-Nasal Allergen Challenge (Post-NAC) to be scored as Yes or No to sneezing at Visit 4 (yes indicates subject is free from sneezing symptom and no indicates subject still has nasal itching symptom). Visit 3 was considered Baseline. Visit 2 was considered an alternate Baseline.

    Time frame: Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.

  10. Nasal Symptom-free Response Rate in TNSS After Prophylaxis Treatment

    Number of subjects that had 25% and 50% reduction in Observed Area Under the Curve (AUC) (0-120 minutes)/Pre-NAC Adjusted AUC (0-120 minutes) at Visit 4 (Day 28) from Visit 2 Observed AUC (0-120 minutes)/Pre-NAC Adjusted AUC (0-120 minutes). For TNSS and Area Under the Curve (AUC) analyses, an Analysis of Covariance with treatment and site as factors and Visit 3 (or Visit 2) value as a covariate was used to test for treatment effect at Visit 4. Observed AUC (0-2 Hours) was defined as TNSS from 0 to 120 minutes post Nasal Allergen Challenge (NAC). The Pre-NAC Adjusted AUC (0-2 Hours) was defined as the observed value minus the 0 minutes prior NAC value.

    Time frame: Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.

Other outcomes

  1. Change in Peak Nasal Inspiratory Flow (PNIF)

    Peak Nasal Inspiratory Flow (PNIF) is a commonly used method for assessing nasal patency and provides an objective measurement of nasal airflow obstruction. The outcome is a direct representation of nasal congestion. Change in PNIF Observed Inverted Area Under the Curve (AUC) was measured between baseline and Visit 4. A decrease in PNIF Observed Inverted AUC(0-2 Hours) was considered an improvement in nasal airflow obstruction. Visit 3 was considered Baseline. Visit 2 was considered an alternate Baseline.

    Time frame: Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.

  2. Nasal Inflammation Score Using Otoscope

    Nasal inflammation were graded by a clinician using a 0-3 nasal inflammation scale based on otoscope measurement where 0 = none, 1 = mild, 2 = moderate, and 3 = severe inflammation 120 minutes Post Nasal Allergen Challenge (Post-NAC).

    Time frame: Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.

  3. Intranasal Nitric Oxide Levels

    Exhaled nasal nitric oxide (NO) was measured from the nasal cavity by a NO analyzer 120 minutes Post Nasal Allergen Challenge (Post-NAC).

    Time frame: Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.

  4. Change in Cytokine Concentration in Nasal Cavity and Blood

    To evaluate if B244 administration will affect the levels of cytokine biomarkers in nasal cavity and blood.

    Time frame: Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.

06

Results

Posted Nov 25, 2022

Participant flow

Study Part 1
Participant flow — Study Part 1
MilestoneVehicleB 244 1x (Low Dose)B244 4x (Mid Dose)
Started888
Completed888
Not completed000
Study Part 2
Participant flow — Study Part 2
MilestoneVehicleB 244 1x (Low Dose)B244 4x (Mid Dose)
Started151616
Completed151616
Not completed000

Outcome measures

PrimaryNumber of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

Safety and tolerability endpoints will consist of all treatment-related adverse events reporting during the study duration for subjects only from Part 1 of the study.

Time frame:
Baseline to Day 28
Reported as:
Count of participants · Participants
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
ParticipantsVehicleB 244 1x (Low Dose)B244 4x (Mid Dose)
Drug Related TEAE000
Drug Related Severe TEAE000
Drug Related Serious TEAE000
SecondaryChange in Total Nasal Symptom Score (TNSS) After Prophylaxis Treatment

Total Nasal Symptom Score (TNSS) is the sum of sub-scores for each of nasal congestion, sneezing, nasal itching, and rhinorrhea at each time point, using a four point scale (0-3; 0 = none; 1 = mild; 2 = moderate; 3 = severe), where 0 indicates no symptoms, a score of 1 for mild symptoms that are easily tolerated, 2 for awareness of symptoms which are bothersome but tolerable and 3 is reserved for severe symptoms that are hard to tolerate and interfere with daily activity. TNSS is calculated by adding the sub-score for each of the symptoms to a total out of 12. For TNSS and Area Under the Curve (AUC) analyses, an Analysis of Covariance with treatment and site as factors and Visit 3 (or Visit 2) value as a covariate was used to test for treatment effect at Visit 4. Observed AUC (0-2 Hours) was defined as TNSS from 0 to 120 minutes post Nasal Allergen Challenge (NAC). The Pre-NAC Adjusted AUC (0-2 Hours) was defined as the observed value minus the 0 minutes prior NAC value.

Time frame:
Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.
Reported as:
Mean · score on a scale*hours
Change in Total Nasal Symptom Score (TNSS) After Prophylaxis Treatment
score on a scale*hoursVehicleB 244 1x (Low Dose)B244 4x (Mid Dose)
Observed AUC (0-2 Hours)-5.1 ± 3.53-2.5 ± 4.51-4.9 ± 3.66
Pre-NAC Adjusted (0-2 Hours)-5.9 ± 3.88-3.7 ± 6.84-4.9 ± 3.29
SecondarySubjective Nasal Symptom Scores of Nasal Congestion After Prophylaxis Treatment

All measurements were taken 120 minutes Post-Nasal Allergen Challenge (Post-NAC) at Visit 4 and compared to Baseline Visit 3. Visit 3 was considered Baseline. Visit 2 was considered an alternate Baseline. Nasal congestion was categorized as None, Mild, Moderate, or Severe.

Time frame:
Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.
Reported as:
Count of participants · Participants
Subjective Nasal Symptom Scores of Nasal Congestion After Prophylaxis Treatment
ParticipantsVehicleB 244 1x (Low Dose)B244 4x (Mid Dose)
Visit 2 (Day 0) — None425
Visit 2 (Day 0) — Mild864
Visit 2 (Day 0) — Moderate054
Visit 2 (Day 0) — Severe333
Visit 3 (Day 14) — None344
Visit 3 (Day 14) — Mild434
Visit 3 (Day 14) — Moderate655
Visit 3 (Day 14) — Severe243
Visit 4 (Day 28) — None347
Visit 4 (Day 28) — Mild866
Visit 4 (Day 28) — Moderate333
Visit 4 (Day 28) — Severe130
SecondarySubjective Nasal Symptom Scores of Rhinorrhea After Prophylaxis Treatment

All measurements were taken 120 minutes Post-Nasal Allergen Challenge (Post-NAC) at Visit 4 and compared to Baseline Visit 3. Visit 3 was considered Baseline. Visit 2 was considered an alternate Baseline. Rhinorrhea was categorized as None, Mild, Moderate, or Severe.

Time frame:
Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.
Reported as:
Count of participants · Participants
Subjective Nasal Symptom Scores of Rhinorrhea After Prophylaxis Treatment
ParticipantsVehicleB 244 1x (Low Dose)B244 4x (Mid Dose)
Visit 2 (Day 0) — None898
Visit 2 (Day 0) — Mild254
Visit 2 (Day 0) — Moderate303
Visit 2 (Day 0) — Severe221
Visit 3 (Day 14) — None566
Visit 3 (Day 14) — Mild655
Visit 3 (Day 14) — Moderate313
Visit 3 (Day 14) — Severe142
Visit 4 (Day 28) — None111010
Visit 4 (Day 28) — Mild234
Visit 4 (Day 28) — Moderate212
Visit 4 (Day 28) — Severe020
SecondarySubjective Nasal Symptom Scores of Nasal Itching After Prophylaxis Treatment

All measurements were taken 120 minutes Post-Nasal Allergen Challenge (Post-NAC) at Visit 4 and compared to Baseline Visit 3. Visit 3 was considered Baseline. Visit 2 was considered an alternate Baseline. Nasal itching was categorized as None, Mild, Moderate, or Severe.

Time frame:
Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.
Reported as:
Count of participants · Participants
Subjective Nasal Symptom Scores of Nasal Itching After Prophylaxis Treatment
ParticipantsVehicleB 244 1x (Low Dose)B244 4x (Mid Dose)
Visit 2 (Day 0) — None61010
Visit 2 (Day 0) — Mild442
Visit 2 (Day 0) — Moderate213
Visit 2 (Day 0) — Severe311
Visit 3 (Day 14) — None679
Visit 3 (Day 14) — Mild454
Visit 3 (Day 14) — Moderate532
Visit 3 (Day 14) — Severe011
Visit 4 (Day 28) — None111113
Visit 4 (Day 28) — Mild433
Visit 4 (Day 28) — Moderate010
Visit 4 (Day 28) — Severe010
SecondarySubjective Nasal Symptom Scores of Sneezing After Prophylaxis Treatment

All measurements were taken 120 minutes Post-Nasal Allergen Challenge (Post-NAC) at Visit 4 and compared to Baseline Visit 3. Visit 3 was considered Baseline. Visit 2 was considered an alternate Baseline. Sneezing was categorized as None, Mild, Moderate, or Severe.

Time frame:
Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.
Reported as:
Count of participants · Participants
Subjective Nasal Symptom Scores of Sneezing After Prophylaxis Treatment
ParticipantsVehicleB 244 1x (Low Dose)B244 4x (Mid Dose)
Visit 2 (Day 0) — None91311
Visit 2 (Day 0) — Mild533
Visit 2 (Day 0) — Moderate102
Visit 2 (Day 0) — Severe000
Visit 3 (Day 14) — None91313
Visit 3 (Day 14) — Mild511
Visit 3 (Day 14) — Moderate121
Visit 3 (Day 14) — Severe001
Visit 4 (Day 28) — None101313
Visit 4 (Day 28) — Mild533
Visit 4 (Day 28) — Moderate000
Visit 4 (Day 28) — Severe000
SecondaryNasal Symptom-free Response Rate in Nasal Congestion Scores After Prophylaxis Treatment

Nasal symptom free response rate was assessed 120 minutes Post-Nasal Allergen Challenge (Post-NAC) to be scored as Yes or No to nasal congestion at Visit 4 (yes indicates subject is free from nasal congestion symptom and no indicates subject still has nasal itching symptom). Visit 3 was considered Baseline. Visit 2 was considered an alternate Baseline.

Time frame:
Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.
Reported as:
Count of participants · Participants
Nasal Symptom-free Response Rate in Nasal Congestion Scores After Prophylaxis Treatment
ParticipantsVehicleB 244 1x (Low Dose)B244 4x (Mid Dose)
Yes347
No12129
SecondaryNasal Symptom-free Response Rate in Rhinorrhea Scores After Prophylaxis Treatment

Nasal symptom free response rate was assessed 120 minutes Post-Nasal Allergen Challenge (Post-NAC) to be scored as Yes or No to rhinorrhea at Visit 4 (yes indicates subject is free from rhinorrhea symptom and no indicates subject still has nasal itching symptom). Visit 3 was considered Baseline. Visit 2 was considered an alternate Baseline.

Time frame:
Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.
Reported as:
Count of participants · Participants
Nasal Symptom-free Response Rate in Rhinorrhea Scores After Prophylaxis Treatment
ParticipantsVehicleB 244 1x (Low Dose)B244 4x (Mid Dose)
Yes111010
No466
SecondaryNasal Symptom-free Response Rate in Nasal Itching Scores After Prophylaxis Treatment

Nasal symptom free response rate was assessed 120 minutes Post-Nasal Allergen Challenge (Post-NAC) to be scored as Yes or No to nasal itching at Visit 4 (yes indicates subject is free from nasal itching symptom and no indicates subject still has nasal itching symptom). Visit 3 was considered Baseline. Visit 2 was considered an alternate Baseline.

Time frame:
Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.
Reported as:
Count of participants · Participants
Nasal Symptom-free Response Rate in Nasal Itching Scores After Prophylaxis Treatment
ParticipantsVehicleB 244 1x (Low Dose)B244 4x (Mid Dose)
Yes111113
No453
SecondaryNasal Symptom-free Response Rate in Sneezing Scores After Prophylaxis Treatment

Nasal symptom free response rate was assessed 120 minutes Post-Nasal Allergen Challenge (Post-NAC) to be scored as Yes or No to sneezing at Visit 4 (yes indicates subject is free from sneezing symptom and no indicates subject still has nasal itching symptom). Visit 3 was considered Baseline. Visit 2 was considered an alternate Baseline.

Time frame:
Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.
Reported as:
Count of participants · Participants
Nasal Symptom-free Response Rate in Sneezing Scores After Prophylaxis Treatment
ParticipantsVehicleB 244 1x (Low Dose)B244 4x (Mid Dose)
Yes101313
No533
SecondaryNasal Symptom-free Response Rate in TNSS After Prophylaxis Treatment

Number of subjects that had 25% and 50% reduction in Observed Area Under the Curve (AUC) (0-120 minutes)/Pre-NAC Adjusted AUC (0-120 minutes) at Visit 4 (Day 28) from Visit 2 Observed AUC (0-120 minutes)/Pre-NAC Adjusted AUC (0-120 minutes). For TNSS and Area Under the Curve (AUC) analyses, an Analysis of Covariance with treatment and site as factors and Visit 3 (or Visit 2) value as a covariate was used to test for treatment effect at Visit 4. Observed AUC (0-2 Hours) was defined as TNSS from 0 to 120 minutes post Nasal Allergen Challenge (NAC). The Pre-NAC Adjusted AUC (0-2 Hours) was defined as the observed value minus the 0 minutes prior NAC value.

Time frame:
Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.
Reported as:
Count of participants · Participants
Nasal Symptom-free Response Rate in TNSS After Prophylaxis Treatment
ParticipantsVehicleB 244 1x (Low Dose)B244 4x (Mid Dose)
25% Reduction from Visit 2 Observed AUC (0-120 minutes) — Yes9612
25% Reduction from Visit 2 Observed AUC (0-120 minutes) — No6104
25% Reduction from Visit 2 Pre-NAC Adjusted AUC (0-120 minutes) — Yes9815
25% Reduction from Visit 2 Pre-NAC Adjusted AUC (0-120 minutes) — No681
50% Reduction from Visit 2 Observed AUC (0-120 minutes) — Yes336
50% Reduction from Visit 2 Observed AUC (0-120 minutes) — No121310
50% Reduction from Visit 2 Pre-NAC Adjusted AUC (0-120 minutes) — Yes768
50% Reduction from Visit 2 Pre-NAC Adjusted AUC (0-120 minutes) — No8108
Other pre-specifiedChange in Peak Nasal Inspiratory Flow (PNIF)

Peak Nasal Inspiratory Flow (PNIF) is a commonly used method for assessing nasal patency and provides an objective measurement of nasal airflow obstruction. The outcome is a direct representation of nasal congestion. Change in PNIF Observed Inverted Area Under the Curve (AUC) was measured between baseline and Visit 4. A decrease in PNIF Observed Inverted AUC(0-2 Hours) was considered an improvement in nasal airflow obstruction. Visit 3 was considered Baseline. Visit 2 was considered an alternate Baseline.

Time frame:
Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.
Reported as:
Mean · L*Hr/min
Change in Peak Nasal Inspiratory Flow (PNIF)
L*Hr/minVehicleB 244 1x (Low Dose)B244 4x (Mid Dose)
Change from Visit 3 to Visit 4-60.8 ± 57.83-8.6 ± 39.62-60.9 ± 57.48
Change from Visit 2 to Visit 4-51.2 ± 99.99-30.4 ± 96.76-59.8 ± 57.77
Other pre-specifiedNasal Inflammation Score Using Otoscope

Nasal inflammation were graded by a clinician using a 0-3 nasal inflammation scale based on otoscope measurement where 0 = none, 1 = mild, 2 = moderate, and 3 = severe inflammation 120 minutes Post Nasal Allergen Challenge (Post-NAC).

Time frame:
Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.
Reported as:
Count of participants · Participants
Nasal Inflammation Score Using Otoscope
ParticipantsVehicleB 244 1x (Low Dose)B244 4x (Mid Dose)
Visit 3 (Day 14) — None000
Visit 3 (Day 14) — Mild548
Visit 3 (Day 14) — Moderate8108
Visit 3 (Day 14) — Severe220
Visit 4 (Day 28) — None226
Visit 4 (Day 28) — Mild995
Visit 4 (Day 28) — Moderate345
Visit 4 (Day 28) — Severe110
Other pre-specifiedIntranasal Nitric Oxide Levels

Exhaled nasal nitric oxide (NO) was measured from the nasal cavity by a NO analyzer 120 minutes Post Nasal Allergen Challenge (Post-NAC).

Time frame:
Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.
Reported as:
Mean · ppb
Intranasal Nitric Oxide Levels
ppbVehicleB 244 1x (Low Dose)B244 4x (Mid Dose)
Visit 3 (Day 14)61.9 ± 57.7733.9 ± 26.6881.9 ± 104.88
Visit 4 (Day 28)63.6 ± 55.4227.3 ± 25.2552.7 ± 41.13
Other pre-specifiedChange in Cytokine Concentration in Nasal Cavity and Blood

To evaluate if B244 administration will affect the levels of cytokine biomarkers in nasal cavity and blood.

Time frame:
Visit 3 (or alternative baseline at Visit 2) to Visit 4 (14 days prophylaxis treatment). Visit 2 was used as an alternate baseline to report baseline values prior to any nasal allergen challenge (NAC) to minimize any potential priming effects.

No measurements were reported for this outcome.

Adverse events

Collected over Part 1: Baseline to end of study (Day 42). Part 2: Baseline to end of study (Day 28).. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Part 1: Vehicle0/8 (0%)0/8 (0%)1/8 (12.5%)
Part 1: B244 1x (Low Dose)0/8 (0%)0/8 (0%)1/8 (12.5%)
Part 1: B244 4x (Mid Dose)0/8 (0%)0/8 (0%)1/8 (12.5%)
Part 2: Vehicle0/15 (0%)0/15 (0%)1/15 (6.7%)
Part 2: B244 1x (Low Dose)0/16 (0%)0/16 (0%)0/16 (0%)
Part 2: B244 4x (Mid Dose)0/16 (0%)0/16 (0%)4/16 (25%)
Most frequent other events
Most frequent other events
EventPart 1: VehiclePart 1: B244 1x (Low Dose)Part 1: B244 4x (Mid Dose)Part 2: VehiclePart 2: B244 1x (Low Dose)Part 2: B244 4x (Mid Dose)
Upper respiratory tract infectionInfections and infestations0/81/80/80/150/161/16
Nasal discomfortRespiratory, thoracic and mediastinal disorders0/80/81/80/150/160/16
Nasal drynessRespiratory, thoracic and mediastinal disorders1/80/80/80/150/160/16
Throat irritationRespiratory, thoracic and mediastinal disorders0/80/80/81/150/160/16
Ear congestionEar and labyrinth disorders0/80/80/80/150/161/16
Chest discomfortGeneral disorders0/80/80/80/150/161/16
HeadacheNervous system disorders0/80/80/80/150/161/16
Nasal congestionRespiratory, thoracic and mediastinal disorders0/80/80/80/150/161/16
WheezingRespiratory, thoracic and mediastinal disorders0/80/80/80/150/161/16
Pain of skinSkin and subcutaneous tissue disorders0/80/80/80/150/161/16

Baseline characteristics

Population includes patients from Part 1 (n=24) Part 2 (n=47) of the study.

Age, Continuous
Age, Continuous(years)VehicleB 244 1x (Low Dose)B244 4x (Mid Dose)Total
Part 147.29 ± 11.17944.60 ± 11.19345.36 ± 10.31645.76 ± 10.477
Part 247.20 ± 9.47045.49 ± 12.14542.30 ± 12.75444.95 ± 11.516
Sex: Female, Male
Sex: Female, Male(Participants)VehicleB 244 1x (Low Dose)B244 4x (Mid Dose)Total
Part 1 — Female35311
Part 1 — Male53513
Part 2 — Female1012931
Part 2 — Male54716
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)VehicleB 244 1x (Low Dose)B244 4x (Mid Dose)Total
Part 1 — Hispanic or Latino35513
Part 1 — Not Hispanic or Latino5218
Part 1 — Unknown or Not Reported0123
Part 2 — Hispanic or Latino3137
Part 2 — Not Hispanic or Latino12151340
Part 2 — Unknown or Not Reported0000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)VehicleB 244 1x (Low Dose)B244 4x (Mid Dose)Total
Part 1 — American Indian or Alaska Native0000
Part 1 — Asian0123
Part 1 — Native Hawaiian or Other Pacific Islander0000
Part 1 — Black or African American2215
Part 1 — White65516
Part 1 — More than one race0000
Part 1 — Unknown or Not Reported0000
Part 2 — American Indian or Alaska Native1001
Part 2 — Asian32611
Part 2 — Native Hawaiian or Other Pacific Islander0000
Part 2 — Black or African American59519
Part 2 — White65516
Part 2 — More than one race0000
Part 2 — Unknown or Not Reported0000
Tobacco History
Tobacco History(Participants)VehicleB 244 1x (Low Dose)B244 4x (Mid Dose)Total
Part 1 — Never88521
Part 1 — Current0000
Part 1 — Former0033
Part 2 — Never12161644
Part 2 — Current0000
Part 2 — Former3003
Screening Height
Screening Height(cm)VehicleB 244 1x (Low Dose)B244 4x (Mid Dose)Total
Part 1174.0 ± 8.20169.8 ± 8.40172.8 ± 11.60172.2 ± 9.24
Part 2169.0 ± 3.73165.9 ± 8.38167.1 ± 9.88167.3 ± 8.39
Screening Weight
Screening Weight(kg)VehicleB 244 1x (Low Dose)B244 4x (Mid Dose)Total
Part 181.83 ± 22.31677.94 ± 10.67989.55 ± 21.37683.10 ± 18.699
Part 276.89 ± 15.27979.69 ± 14.57779.72 ± 17.63378.81 ± 15.604
Screening BMI
Screening BMI(kg/m^2)VehicleB 244 1x (Low Dose)B244 4x (Mid Dose)Total
Part 126.77 ± 5.89027.15 ± 4.19729.76 ± 5.01327.89 ± 5.046
Part 226.86 ± 4.80328.93 ± 4.86828.59 ± 6.05328.15 ± 5.250
07

Study locations

2 sites
  • Orange County Research Center
    Tustin, California 92780, United States
  • Inflamax
    Mississauga, Ontario M6G 3V1, Canada
08

References and documents

Study documents

  • Study protocol · Aug 29, 2018
  • Statistical analysis plan · Jan 3, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03290248
Lead sponsor
AOBiome LLC
Collaborators
Orange County Research Center, Integrium
Responsible party
Sponsor
First posted
Sep 21, 2017
Start date
Sep 19, 2017
Primary completion
Dec 21, 2018
Completion
Dec 21, 2018
Results posted
Nov 25, 2022
Last update
Nov 25, 2022

Study contacts

Joel Neutel, MD
principal investigator · Study PI

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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