Study Examining PrEP-001 in Healthy Subjects

Screening took place up to 90 days before quarantine. Volunteers completed an informed consent and underwent screening assessments to determine their eligibility.

There were 2 study groups:

Cohort A: (Sentinel): determined the Challenge Virus infection rate after inoculation with Influenza Virus on Day 0. There was 12 subjects (open label, no randomisation) invited to attend Quarantine on Day -2 or -1.

Cohort B: Examined the prophylactic efficacy, safety and tolerability of PrEP-001 compared to placebo (randomised 1:1). Subjects attended on Day -4/-3, dosed with PrEP-001 or Placebo on Day -2 AND Day-1 and then challenged with virus (volume confirmed from Cohort A) on Day 0.

Volunteers remained in quarantine unit for 8 days after inoculation.

At day 28, end of study visit, volunteers seen and assessed by a study physician for well-being, on-going symptoms and adverse events.

• PrEP-001 (Drug), also known as JNJ-43260295-AAM
• Placebo Comparator (Other), also known as G-004

Primary outcomes

• Primary Efficacy Endpoint: The Area Under the Curve (AUC) of Total Symptom Score From Day 1 (Post Viral Challenge) to Day 8 (Quarantine Discharge). [8 days]: Area Under the Curve (AUC) of total symptom scores (upper respiratory tract (URT), lower respiratory tract (LRT) and systemic viral symptoms (SVS)). Total symptom scores (from the symptom diary card) were used to calculate the AUC. The time unit used was minutes. Thus, the AUC unit is the total symptom score multiplied by the time period from first to last assessment in minutes (i.e score*mins). The minimum AUC value would be 0, for a subject who did not report any symptoms. The maximum AUC value is not provided as it would be theoretical only, with no real meaning in terms of severity. Higher scores indicate worse outcome than lower scores.

Secondary outcomes

• Secondary Efficacy Endpoint: Symptom Scores: Peak Symptoms Score [8 days]: Using the scheduled protocol assessments from Day 1 to Day 8, this endpoint represented the highest total symptom score (defined as the sum of all 10 individual composite symptoms). The minimum value, for subjects who had no symptoms, would be 0. The maximum value would be 30. Higher scores indicate worse outcome than lower scores.
• Secondary Efficacy Endpoint: Incidence(s) of Illness and Infection: Viral Shedding [8 days]: The number of subjects with viral shedding. Viral shedding was measured by PCR, testing the nasopharyngeal swab samples.
• Secondary Efficacy Endpoint: Incidence(s) of Illness and Infection: Seroconversion [8 days]: The number of subjects with seroconversion. Seroconversion was measured by the ratio of Influenza A/Perth/16/2009 (H3N2) virus antibodies at follow-up versus pre-dose.
• Secondary Efficacy Endpoint: Viral Load Parameters: Area Under the Curve (AUC) of Viral Load, as Measured by Nasopharyngeal Swab RT-qPCR. [8 days]: Viral load data was supplied in Log10 Copies/mL. These values were used to calculate the Area Under the Curve (AUC) of Viral Load for each subject.
• Secondary Efficacy Endpoint: Total Weight of Nasal Discharge Produced Post Viral Challenge to Quarantine Discharge [8 days]: Total weight of nasal discharge (in grams) was calculated as the sum of mucus weights taken from Day 1 (Post viral challenge) to Day 8 (Quarantine Discharge).

Sex: All, ages: 18 Years to 55 Years, accepts healthy volunteers

Inclusion Criteria:

* Young healthy adults as determined by medical history, physical examination, serology (HIV and Hepatitis B and C) and clinical laboratory tests.
* Female subjects were required to provide of a history of reliable contraceptive practice.

Exclusion criteria:

* Subjects who have a significant history of any tobacco use at any time.
* Any history or evidence of any clinically significant cardiovascular, dermatological gastrointestinal, endocrinological, haematological, hepatic, immunological, metabolic, urological, neurological, psychiatric, renal disease.
* Abnormal ECG

Participant flow

Outcome results

• Primary Efficacy Endpoint: The Area Under the Curve (AUC) of Total Symptom Score From Day 1 (Post Viral Challenge) to Day 8 (Quarantine Discharge). (Primary), Mean, score*mins: Cohort A: Sentinel Group 17956.5 +/- 23780.83; Cohort B: PrEP-001 4502.6 +/- 6144.84; Cohort B: Placebo 9859.6 +/- 12215.84
• Secondary Efficacy Endpoint: Symptom Scores: Peak Symptoms Score (Secondary), Mean, Score: Cohort A: Sentinel Group 5.2 +/- 5.88; Cohort B: PrEP-001 1.7 +/- 1.9; Cohort B: Placebo 3.3 +/- 3.28
• Secondary Efficacy Endpoint: Incidence(s) of Illness and Infection: Viral Shedding (Secondary), Count of participants, Participants: Cohort A: Sentinel Group 7; Cohort B: PrEP-001 13; Cohort B: Placebo 21
• Secondary Efficacy Endpoint: Incidence(s) of Illness and Infection: Seroconversion (Secondary), Count of participants, Participants: Cohort A: Sentinel Group 9; Cohort B: PrEP-001 12; Cohort B: Placebo 16
• Secondary Efficacy Endpoint: Viral Load Parameters: Area Under the Curve (AUC) of Viral Load, as Measured by Nasopharyngeal Swab RT-qPCR. (Secondary), Mean, mins*log10 copy number/mL: Cohort A: Sentinel Group 33021.8 +/- 19676.07; Cohort B: PrEP-001 23781.6 +/- 14127.65; Cohort B: Placebo 32944.4 +/- 17059.07
• Secondary Efficacy Endpoint: Total Weight of Nasal Discharge Produced Post Viral Challenge to Quarantine Discharge (Secondary), Mean, grams: Cohort A: Sentinel Group 26.580 +/- 49.5158; Cohort B: PrEP-001 3.959 +/- 5.1349; Cohort B: Placebo 13.414 +/- 20.7986

Adverse events

Other adverse events by term

• Results publication: Malcolm BA, Aerts CA, Dubois KJ, Geurts FJ, Marien K, Rusch S, Van Dijck AH, Verloes R, Vingerhoets J. PrEP-001 prophylactic effect against rhinovirus and influenza virus - RESULTS of 2 randomized trials. Antiviral Res. 2018 May;153:70-77. doi: 10.1016/j.antiviral.2018.03.005. Epub 2018 Mar 19. PMID 29567461

• John Efthimiou, Study chair, Sponsor's representative