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HIV PreventionPhase 1DREAM-01NCT02750540

Optimization of a Tenofovir Enema for HIV Prevention

A Phase 1 study testing Tenofovir enema and Saline enema in people with HIV Prevention, run by Johns Hopkins University at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

DREAM-01 is an early phase 1, open label, dose-escalation and variable osmolarity study to compare the safety, pharmacokinetics (PK), pharmacodynamics (PD), and acceptability of 3 formulations of a tenofovir (TFV) enema. Read more about this study

Who is it for?
Ages 18 years and older, men onlyHealthy volunteers can take part
Conditions the study is for
HIV Prevention
What is being tested?
Tenofovir enema and Saline enema
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
21 participants
Where
3 sitesUnited States
Study dates
Oct 2016to May 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 18 years of age or older at screening
  • Willing and able to communicate in English
  • Willing and able to provide written informed consent to take part in the study
  • Willing and able to provide adequate locator information
  • Understand and agree to local Sexually Transmitted Infection (STI) reporting requirements
  • Biologically male
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  • HIV-1 uninfected at screening as documented by Combo Ag/Ab HIV-1/HIV-2 immunoassay (refer to Appendix II for confirmatory testing algorithm)
  • Available to return for all study visits, barring unforeseen circumstances
  • Per participant report at screening, a history of consensual Receptive Anal Intercourse (RAI) at least five times in lifetime and at least once in the prior 3 months (Required to ensure that participants are sufficiently sexually active to complete take-home enema study requirements)
  • Per participant report at screening, experience with receiving or self-administering an enema or douche in the past year.
  • Willing to abstain from insertion of anything (drug/medication, penis, object, sex toy, or enema including take-home enema) into the anorectum for 72 hours before and after each research unit study product exposure and 7 days after each flexible sigmoidoscopy with biopsy collection.
  • Willing to refrain from aspirin and NSAID use for one week before and after each study biopsy visit
  • Willing and able to use condoms provided by the study for all Receptive Anal Intercourse (RAI) for the duration of participation
  • Agrees not to participate in other research studies involving drugs and/ or medical devices for the duration of the study

Who cannot join

  • History of chronic Hepatitis B infection, as documented by positive HBsAg at screening
  • ≥ Grade 2 laboratory abnormality at baseline as defined by The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0 dated November 2014
  • Significant colorectal symptom(s) as determined by medical history or by participant self-report (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, history of inflammatory bowel disease, presence of symptomatic external hemorrhoids, and presence of any painful anorectal conditions that would be tender to manipulation)
  • At screening or within the past 2 months: participant-reported symptoms and/or clinical or laboratory diagnosis of active rectal or reproductive tract infection requiring treatment per current Centers for Disease Control and Prevention (CDC) guidelines or symptomatic urinary tract infection (UTI). Infections requiring treatment include Chlamydia (CT), gonorrhea (GC), syphilis, active Herpes Simplex Virus (HSV) lesions, chancroid, genital sores or ulcers, and, if clinically indicated, genital warts. Note that HSV seropositivity with no active genital lesions is not an exclusion criterion, since treatment is not required.
  • History of an underlying cardiac arrhythmia or renal disease (including creatinine clearance <50 mL/min using Cockcroft-Gault equation)
  • History of severe or recent cardiac or pulmonary event
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  • History of aortic aneurysm
  • History of significant gastrointestinal bleeding
  • Current use of warfarin or heparin or other anticoagulant medications associated with increased risk for bleeding following mucosal biopsy (e.g., daily high dose aspirin [>81 mg], NSAIDs, or Pradaxa®)
  • Use of systemic or anorectal immunomodulatory medications within 4 weeks of enrollment or planned use at any time during study participation
  • Use of pre-exposure (PrEP) and post-exposure (PEP) prophylaxis for HIV exposure within 3 weeks of enrollment or planned use within 3 weeks prior to any study visit with PK sampling.
  • Per participant report, use of any rectally administered products containing N-9 (including condoms) or investigational products within 4 weeks of enrollment, or planned use of either at any time during study participation
  • Known allergic reaction to TFV or other components of the test articles
  • Current known HIV-infected partners
  • History of recurrent urticaria
  • For JHU only: Participants whose whole body (Effective Dose Equivalent or EDE) radiation exposure, per the investigator's records and/or participant report, exceeds 5000 Millirem (mRem)/year
  • Symptoms suggestive of acute HIV seroconversion at screening and enrollment
  • Any other condition or prior therapy that, in the opinion of the investigator, would preclude informed consent, make study participation unsafe, make the individual unsuitable for the study or unable to comply with the study requirements. Such conditions may include, but are not limited to, current or recent history of severe, progressive, or uncontrolled substance abuse, or renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, or cerebral disease.

Trial locations and contacts

3 sites in 1 country.

United States3 sites
  • The Johns Hopkins University

    Baltimore, Maryland, 21287

  • Center for Prevention Research, University of California Los Angeles

    Los Angeles, California, 90024

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

Other trials in United States

About this study

Official title: DREAM-01: Optimization of a Tenofovir Enema for HIV Prevention

DREAM-01 is an early phase 1, open label, dose-escalation and variable osmolarity study to compare the safety, pharmacokinetics (PK), pharmacodynamics (PD), and acceptability of 3 formulations of a tenofovir (TFV) enema. The goal of the study is to identify the dose and osmolarity of a TFV enema for human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) which achieves the desired colonic mucosal mononuclear cells (MMC) tenofovir diphosphate (TFV-DP) target concentrations that have previously been shown to confer protection from HIV acquisition in men who have sex with men (MSM).

Read the detailed description

DREAM-01 is an early phase 1, open label, dose-escalation and variable osmolarity study to compare the safety, pharmacokinetics (PK), pharmacodynamics (PD), and acceptability of 3 formulations of a tenofovir (TFV) enema. The goal of the study is to identify the dose and osmolarity of a TFV enema for human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) which achieves the desired colonic mucosal mononuclear cells (MMC) tenofovir diphosphate (TFV-DP) target concentrations that have previously been shown to confer protection from HIV acquisition in men who have sex with men (MSM).

Each participant will undergo screening to evaluate eligibility. Baseline visit will assess safety, PD, and behavioral readout baselines. Three products described below (Product A, B, and C) are dosed sequentially as a dose-escalation within each subject. Safety, PK, PD, and behavioral readouts are assessed at specified times for one week after each dose, followed by a variable washout period before the next escalation dose. Johns Hopkins University (JHU) participants only will have SPECT/CT imaging to assess distribution and permeability of radiolabeled product. After two of the study product doses (Product A and Product C) and their respective sampling periods, a normal saline (NS) solution and ½ normal saline (½ NS) solution will be taken at home in the context of receptive anal intercourse.

Study Duration: Participant accrual will take approximately 9 months and each participant will be on study for approximately 4-5 months. Total study duration is about 1 year.

Study Products: Three study products administered sequentially and estimated to approximate TFV 1% gel (Product A), 3 times the concentration and dose of Product A (Product B), and 2 times concentration and dose of Product B (Product C) as defined below. At JHU only, the study product will also be radiolabeled with Technetium-99m-DTPA (99mTc-DTPA) for SPECT/CT imaging. Take-home enemas consisting of normal saline (NS) or ½ normal saline (½ NS) will be self-administered at home.

  • Product A: Enema formulation of TFV 1.76 mg/mL (220 mg in 125 mL) in iso-osmolar solution
  • Product B: Enema formulation of TFV 5.28 mg/mL (*660 mg in 125 mL) in iso-osmolar solution
  • Product C: Rectal specific Enema formulation of TFV 5.28 mg/mL (*660 mg in 125 mL) in hypo-osmolar solution
  • Take-home enema to follow Product A: 120 mL of normal saline (NS) solution
  • Take-home enema to follow Product C: ½ normal saline (½ NS)
  • Note: the planned 660 mg TFV dose in Product B and C may be adjusted lower or higher based on Product A results in order to more closely achieve target concentrations - this is indicated by *660 mg, which will be used throughout the protocol to indicate the planned, but potentially modified Product B (or C as the case may be) dose.
Conditions
HIV Prevention
Being tested
Tenofovir enema, Saline enema
Keywords
Tenofovir enema

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tenofovir enemaDrug

  • Saline enemaOther

Study groups in NCT02750540
Study groupRoleWhat they receive
Product A doseActive comparatorProduct A will contain tenofovir (TFV) 220 mg in 125 mL iso-osmolar solution: Participants will have a single dose administered in clinic or a research unit, followed by various specimen collections over 8 days, according to individual sampling schedule assigned to each participant; specimens will be collected on Day 1, 2, 4, and 8.
Receives: Drug: Tenofovir enema
Product B doseActive comparatorProduct B will contain tenofovir (TFV) *660 mg in 125 mL iso-osmolar solution: Participants will have a single dose administered in clinic or a research unit, followed by various specimen collections over 8 days, according to individual sampling schedule assigned to each participant; specimens will be collected on Day 1, 2, 4, and 8.
Receives: Drug: Tenofovir enema
Product C doseActive comparatorProduct C will contain tenofovir (TFV) *660 mg in 125 mL hypo-osmolar solution at half the osmolarity of iso-osmolar solution: Participants will have a single dose administered in clinic or a research unit, followed by various specimen collections over 8 days, according to individual sampling schedule assigned to each participant; specimens will be collected on Day 1, 2, 4, and 8.
Receives: Drug: Tenofovir enema
Take-home normal saline (NS) enemaPlacebo comparatorThe normal saline (NS) solution will be provided following administration of Product A which is iso-osmolar. The volume of NS enema (120 mL) was selected to approximately match that of Product A (125 mL)
Receives: Other: Saline enema
Take-home half normal saline (½ NS) enemaPlacebo comparatorThe ½ normal saline (½ NS) solution will be provided following administration of Product C which is hypo-osmolar. The volume of the ½ NS enema (120 mL) was selected to approximately match that of Product C (125 mL)
Receives: Other: Saline enema

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Occurrence of adverse events Grade 2 or higher, using Division of AIDS Adverse Events Grading Tables

    Adverse events occurring between dosing and day 7 for each of 3 doses during the study (each will be assessed as a unique dose related event period lasting 7 days) will be assessed according to the following scale: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening

    Measured: A total number of adverse events will be assessed through study completion, time period of up to 9 months

  2. Area under the curve of tenofovir concentration matrix at 1 hr post dose

    TFV-DP concentration will be measured at 1 hr post dose in order to assess target concentrations in colonic mucosal mononuclear cells (MMC) for each study product

    Measured: 1 hr post dose

  3. Area under the curve of tenofovir concentration matrix at 3 hr post dose

    TFV-DP concentration will be measured at 3 hr post dose in order to assess target concentrations in colonic mucosal mononuclear cells (MMC) for each study product

    Measured: 3 hr post dose

  4. Area under the curve of tenofovir concentration matrix at 6 hr post dose

    TFV-DP concentration will be measured at 6 hr post dose in order to assess target concentrations in colonic mucosal mononuclear cells (MMC) for each study product

    Measured: 6 hr post dose

  5. Area under the curve of tenofovir concentration matrix at 12 hr post dose

    TFV-DP concentration will be measured at 12 hr post dose in order to assess target concentrations in colonic mucosal mononuclear cells (MMC) for each study product

    Measured: 12 hr post dose

  6. Area under the curve of tenofovir concentration matrix at 24 hr post dose

    TFV-DP concentration will be measured at 24 hr post dose in order to assess target concentrations in colonic mucosal mononuclear cells (MMC) for each study product

    Measured: 24 hr post dose

  7. Area under the curve of tenofovir concentration matrix at 72 hr post dose

    TFV-DP concentration will be measured at 72 hr post dose in order to assess target concentrations in colonic mucosal mononuclear cells (MMC) for each study product

    Measured: 72 hr post dose

  8. Area under the curve of tenofovir concentration matrix at 168 hr post dose

    TFV-DP concentration will be measured at 168 hr post dose in order to assess target concentrations in colonic mucosal mononuclear cells (MMC) for each study product

    Measured: 168 hr post dose

  9. Proportion of subjects who consider the tenofovir study products acceptable for use as assessed by a behavioral questionnaire

    For each product, descriptive statistics of overall product acceptability will be generated (i.e., mean and standard deviation for continuous variables and proportion of subjects who consider the products acceptable -- with score 3 or greater). In addition, a futility test will be conducted for each product to screen out non-acceptable product(s) and identify the product(s) with potential for being acceptable to users in a future study. The acceptability of each product is defined as a mean score of 3 on 4-point continuous acceptability measure (1=completely unacceptable; 2=somewhat unacceptable; 3=somewhat acceptable; 4=highly acceptable) that is defined in this study as the minimal clinically meaningful threshold for product acceptability.

    Measured: After each TFV enema product (at 1 to 6 hours post dose)

  10. Proportion of subjects who consider using the saline enemas at home acceptable as assessed by a behavioral questionnaire

    Descriptive statistics of overall product acceptability will be generated (i.e., mean and standard deviation for continuous variables and proportion of subjects who consider the products acceptable -- with score 3 or greater). In addition, a futility test will be conducted for each product to screen out non-acceptable product(s) and identify the product(s) with potential for being acceptable to users in a future study. The acceptability of each product is defined as a mean score of 3 on 4-point continuous acceptability measure (1=completely unacceptable; 2=somewhat unacceptable; 3=somewhat acceptable; 4=highly acceptable) that is defined in this study as the minimal clinically meaningful threshold for product acceptability.

    Measured: Within 30 days after completing the low dose TFV enema use and high dose TFV enema use in clinic

  11. Proportion of subjects who consider all enema study products acceptable for use as assessed by a behavioral questionnaire

    Descriptive statistics of overall product acceptability will be generated (i.e., mean and standard deviation for continuous variables and proportion of subjects who consider the products acceptable -- with score 3 or greater). In addition, a futility test will be conducted for each product to screen out non-acceptable product(s) and identify the product(s) with potential for being acceptable to users in a future study. The acceptability of each product is defined as a mean score of 3 on 4-point continuous acceptability measure (1=completely unacceptable; 2=somewhat unacceptable; 3=somewhat acceptable; 4=highly acceptable) that is defined in this study as the minimal clinically meaningful threshold for product acceptability.

    Measured: At the end of each subject's study participation, after all 3 products have been administered in clinic and at home, which is up to 1 month after the last product is administered at home. The total period of study depends on interim data analysis.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2016 (estimated)
  2. Study startOct 2016
  3. Primary completionMay 2019
  4. Study completionMay 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02750540
Sponsor's protocol ID
IRB00097186
Other IDs
DAIDS ES 12067, 5U19AI113127
Acronym
DREAM-01
Status last verified
Feb 2024
First submitted
11 Apr 2016
Last updated
7 Feb 2024
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Giguere R, Balan IC, Lentz C, Dolezal C, Carballo-Dieguez A, Fuchs EJ, Anton P, McGowan I, Ho K, Weld E, Hendrix CW. Acceptability of a rectal microbicide douche for HIV prevention: a mixed-methods analysis of a first-in-human formulation pilot study. Sex Transm Infect. 2025 Jan 29;101(1):49-54. doi: 10.1136/sextrans-2024-056209.

    PubMed 39237135
  • Weld ED, McGowan I, Anton P, Fuchs EJ, Ho K, Carballo-Dieguez A, Rohan LC, Giguere R, Brand R, Edick S, Bakshi RP, Parsons T, Manohar M, Seigel A, Engstrom J, Elliott J, Jacobson C, Bagia C, Wang L, Al-Khouja A, Hartman DJ, Bumpus NN, Spiegel HML, Marzinke MA, Hendrix CW. Tenofovir Douche as HIV Preexposure Prophylaxis for Receptive Anal Intercourse: Safety, Acceptability, Pharmacokinetics, and Pharmacodynamics (DREAM 01). J Infect Dis. 2024 Apr 12;229(4):1131-1140. doi: 10.1093/infdis/jiad535.

    PubMed 38019657

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tenofovir enema and Saline enema in people with HIV Prevention, run by Johns Hopkins University at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Occurrence of adverse events Grade 2 or higher, using Division of AIDS Adverse Events Grading Tables (time frame: A total number of adverse events will be assessed through study completion, time period of up to 9 months). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02750540, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2024.

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