| Primary | Percentage of Participants Achieving Complete Response in 5-FU Arm and Observation Arm Using ITT Population | Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. The percentage of participants achieving complete response in the 5-FU and observation arms will be reported and compared across sites, along with the corresponding p-value, using stratified Mantel-Haenszel-Cochran tests at a one-sided alpha level of 0.025. | | Posted | | Count of Participants | | Participants | | At week 20 | | | | ID | Title | Description |
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| OG000 | Arm C (Observation) | Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B. | | OG001 | Arm B (Fluorouracil) | Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. fluorouracil: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies |
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| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
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| | Cochran-Mantel-Haenszel | | 0.1877 | The threshold for statistical significance was p=0.05. | | | | | | | | | | | | | Superiority | | |
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| Primary | Percentage of Participants Achieving Complete Response (5-FU vs Observation ) Using Per Protocol Population | Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. The percentage of participants achieving complete response in the 5-FU and observation arms will be reported, along with the corresponding p-value, using stratified Mantel-Haenszel-Cochran tests to compare results across sites at a one-sided alpha level of 0.025. | | Posted | | Count of Participants | | Participants | | At week 20 | | | | ID | Title | Description |
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| OG000 | Arm B (Fluorouracil) | Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. fluorouracil: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG001 | Arm C (Observation) | Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B. |
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| Primary | Percentage of Participants Achieving Complete Response in 5-FU vs. Imiquimod, Using the ITT Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm. | Complete response is defined as an absence of HSIL histology for all biopsies and the absence of HSIL cytology. Compare the percentage of complete response in 5-FU vs Imiquimod arms across sites using stratified CMH test at one-sided 0.05 alpha. | ITT population. Since the imiquimod arm was stopped early, this comparison uses only the ITT subset with participants randomized to imiquimod and 5-FU prior to closure of the imiquimod arm. | Posted | | Count of Participants | | Participants | | Week 20 | | | | ID | Title | Description |
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| OG000 | Arm A (Imiquimod) | Patients apply imiquimod intra-anally QD for 16 weeks. imiquimod: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG001 | Arm B (Fluorouracil) | Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. fluorouracil: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies |
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| Primary | Percentage of Participants Achieving Complete Response in 5-FU vs. Imiquimod, Using the PP Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm. | Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. Compare the complete response by 5-FU vs Imiquimod across sites using stratified CMH test at one-sided 0.05 alpha using only the participants randomized to imiquimod and 5-FU prior to closure of the imiquimod arm. | PP population restricted to those randomized to either treatment prior to the closure of the imiquimod | Posted | | Count of Participants | | Participants | | Week 20 | | | | ID | Title | Description |
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| OG000 | Arm A (Imiquimod) | Patients apply imiquimod intra-anally QD for 16 weeks. imiquimod: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG001 | Arm B (Fluorouracil) | Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. fluorouracil: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies |
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| Primary | Percentage of Participants Achieving Complete Response in Imiquimod vs Observation Arm, Using ITT Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm. | Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. Compare the complete response by Observation vs Imiquimod across sites using stratified CMH test at two-sided 0.05 alpha using only the participants randomized to imiquimod and observation prior to closure of the imiquimod arm. | ITT population restricted to those randomized to either treatment prior to the closure of the imiquimod arm. | Posted | | Count of Participants | | Participants | | Week 20 | | | | ID | Title | Description |
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| OG000 | Arm A (Imiquimod) | Patients apply imiquimod intra-anally QD for 16 weeks. imiquimod: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG001 | Arm C (Observation) | Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B. |
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| Primary | Percentage of Participants Achieving Complete Response in Imiquimod vs Observation Arm, Using Per Protocol Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm. | Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. Compare the complete response by Observation vs Imiquimod across sites using stratified CMH test at two-sided 0.05 alpha using only the participants randomized to imiquimod and observation prior to closure of the imiquimod arm. | PP population restricted to those randomized to either treatment prior to the closure of the imiquimod arm. | Posted | | Count of Participants | | Participants | | Week 20 | | | | ID | Title | Description |
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| OG000 | Arm A (Imiquimod) | Patients apply imiquimod intra-anally QD for 16 weeks. imiquimod: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG001 | Arm C (Observation) | Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B. |
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| Primary | Number of Participants With Peri-anal HSIL Confirmed by Histology Across All Study Arms | Perianal HSIL are HSIL lesions detected in peri-anal region; These lesions will be detected by visual inspection using high resolution anoscopy and biopsy. Number of participants with presence of peri-anal HSIL on histology | Enrolled patients in each study arm | Posted | | Count of Participants | | Participants | | At week 20 | | | | ID | Title | Description |
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| OG000 | Arm A (Imiquimod) | Patients apply imiquimod intra-anally QD for 16 weeks. imiquimod: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG001 | Arm B (Fluorouracil) | Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. fluorouracil: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG002 | Arm C (Observation) | Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B. |
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| Primary | Number of Participants With Intra-anal HSIL | Intra-anal HSIL lesions are those lesions that are detected in intra-anal region. It will be detected using visual inspection using HRA followed by positive identification of HSIL using biopsy or cytology. Presence of intra-anal HSIL lesions will be descriptively reported across the three arms | | Posted | | Count of Participants | | Participants | | At week 20 | | | | ID | Title | Description |
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| OG000 | Arm A (Imiquimod) | Patients apply imiquimod intra-anally QD for 16 weeks. imiquimod: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG001 | Arm B (Fluorouracil) | Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. fluorouracil: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG002 | Arm C (Observation) | Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B. |
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| Secondary | Number of Participants Who Experienced an Adverse Event of Grade 1 to 5 by Week 44, Irrespective of Relatedness to the Intervention. AEs Were Stratified According to Those Reported at or Before Week 20 and After Week 20. | Adverse events are graded on a scale from 1 (mild) to 5 (death) as per CTCAE v. 5.0, with higher grades indicating greater severity. The number of participants who experienced an adverse event of grade 1 to 5 by Week 44, regardless of its relatedness to the intervention, will be reported. AEs were stratified according to those reported at or before Week 20 and after Week 20. | | Posted | | Count of Participants | | Participants | | Up to week 44 | | | | ID | Title | Description |
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| OG000 | Arm A (Imiquimod)- Up to Week 44 | Patients apply imiquimod intra-anally QD for 16 weeks. imiquimod: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG001 | Arm B (Fluorouracil)- Up to Week 44 | Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. fluorouracil: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG002 | Arm C (Observation)- Up to Week 20 |
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| Secondary | Percentage of Participants Achieving Complete or Partial Response in 5-FU vs Observation Using ITT Population | Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. Partial response is defined as either 1) The regression of HSIL histology but HSIL cytology is present, or 2) Reduction in number of octants with HSIL. Percentages will be compared across sites using the stratified Mantel-Haenszel-Cochran test at the two-sided 0.05 alpha level. | | Posted | | Count of Participants | | Participants | | Up to week 20 | | | | ID | Title | Description |
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| OG000 | Arm B (Fluorouracil) | Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. fluorouracil: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG001 | Arm C (Observation) | Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B. |
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| Secondary | Percentageof Patients Achieving Complete or Partial Response in Imiquimod vs Observation Arm, Using ITT Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm. | Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. Partial response is defined as 1) The regression of HSIL histology but HSIL cytology is present, or 2) Reduction in number of octants with HSIL. Percentage of patients achieving complete or partial responses with imiquimod will be compared to observation using participants randomized to imiquimod and observation prior to closure of the imiquimod arm. | ITT population restricted to those randomized to either treatment prior to the closure of the imiquimod arm. | Posted | | Count of Participants | | Participants | | Up to week 20 | | | | ID | Title | Description |
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| OG000 | Arm A (Imiquimod) | Patients apply imiquimod intra-anally QD for 16 weeks. imiquimod: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG001 | Arm C (Observation) | Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B. |
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| Secondary | Amount of Drug Consumed in 5-FU and Imiquimod Arm by Week 16 | Amount of study drug consumed by measuring the mass of study drug dispensed (weight of study drug container at baseline - weight of study drug at the end of treatment) by study arm (5FU vs imiquimod) by the time of receiving 8 cycle treatment | | Posted | | Mean | Standard Deviation | grams | | Week 16 | | | | ID | Title | Description |
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| OG000 | Arm A (Imiquimod) | Patients apply imiquimod intra-anally QD for 16 weeks. imiquimod: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG001 | Arm B (Fluorouracil) | Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. fluorouracil: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies |
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| Secondary | Percentage of Participants Achieving Complete or Partial Response in 5-FU vs Observation Using ITT Population | Complete response is defined as the Complete response is defined as the absence of HSIL histology for all biopsies and the absence of HSIL cytology. Partial response is defined as 1) The regression of HSIL histology but HSIL cytology is present, or 2) Reduction in number of octants with HSIL. Percentage will be compared across sites using the stratified Mantel-Haenszel-Cochran test at the two-sided 0.05 alpha level. | | Posted | | Count of Participants | | Participants | | At 44 weeks | | | | ID | Title | Description |
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| OG000 | Arm B (Fluorouracil) | Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. fluorouracil: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG001 | Arm C (Observation) | Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B. |
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| Secondary | Percentage of Patients Achieving Complete or Partial Response in Imiquimod vs Observation Arm, Using ITT Population Restricted to Those Randomized to Either Treatment Prior to the Closure of the Imiquimod Arm. | The proportion of patients achieving complete or partial responses with imiquimod will be compared to observation using participants randomized to imiquimod and observation prior to closure of the imiquimod arm. Complete response is defined as the absence of HSIL based on central pathology review, if available; otherwise, local biopsy results will be used. Partial Response is defined as: 1) The regression of HSIL histology but HSIL cytology is present, or 2) Reduction in number of octants with HSIL. | ITT population restricted to those randomized to either treatment prior to the closure of the imiquimod arm. | Posted | | Count of Participants | | Participants | | Up to week 44 | | | | ID | Title | Description |
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| OG000 | Arm A (Imiquimod) | Patients apply imiquimod intra-anally QD for 16 weeks. imiquimod: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG001 | Arm C (Observation) | Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B. |
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| Secondary | Persistence and New Infections of HPV Type Specific Infections | The proportion of participants with persistent HPV infection, defined as the presence of the same HPV type detected at both baseline and Week 20. The proportion of participants who acquire a new HPV infection at Week 20 that was not detected at baseline is new infection. Persistence and new infection will be assessed separately for each HPV type. | | Posted | | Count of Participants | | Participants | | At week 20 | | | | ID | Title | Description |
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| OG000 | Arm A (Imiquimod) | Patients apply imiquimod intra-anally QD for 16 weeks. imiquimod: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG001 | Arm B (Fluorouracil) | Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. fluorouracil: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG002 | Arm C (Observation) | Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B. |
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| Secondary | Comparison of the Number of hrHPV Genotypes in Each Arm Observed at Baseline vs at Week 20 | hrHPV genotypes will be detected in anal swabs specimens processed using polymerase chain reaction (PCR) and reverse line blot analysis. Comparison of mean number of hrHPV genotypes in each arm observed at baseline vs at week 20 | | Posted | | Mean | Standard Deviation | hrHPV genotypes | | week 20 | | | | ID | Title | Description |
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| OG000 | Arm A (Imiquimod) | Patients apply imiquimod intra-anally QD for 16 weeks. imiquimod: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG001 | Arm B (Fluorouracil) | Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. fluorouracil: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG002 | Arm C (Observation) | Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B. |
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| Secondary | HPV Genotypes Present at Baseline But no Longer Detected at Week 20 | Count of HPV genotypes present at baseline but no longer detected at week 20. | | Posted | | Count of Units | | Unique HPV genotypes | | 20 weeks | Unique HPV genotypes | Unique HPV genotypes | | ID | Title | Description |
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| OG000 | Arm A (Imiquimod) | Patients apply imiquimod intra-anally QD for 16 weeks. imiquimod: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG001 | Arm B (Fluorouracil) | Patients apply fluorouracil intra-anally BID on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. fluorouracil: Given intra-anally questionnaire administration: Ancillary studies laboratory biomarker analysis: Correlative studies | | OG002 | Arm C (Observation) | Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B. |
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