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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03198559




Registration number
NCT03198559
Ethics application status
Date submitted
14/06/2017
Date registered
26/06/2017

Titles & IDs
Public title
Combination Latency Reversal With High Dose Disulfiram Plus Vorinostat in HIV-infected Individuals on ART
Scientific title
Combination Latency Reversal With High Dose Disulfiram Plus Vorinostat in HIV-infected Individuals on ART (DIVA): A Single Arm Clinical Trial
Secondary ID [1] 0 0
MSD IIS-55750
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Disulfiram, (National Drug Code) NDC 0378-4141-01
Treatment: Drugs - Vorinostat, NDC 00006-0568-40

Experimental: Experimental - Participants current ART regimen:

2 grams disulfiram by mouth per day for a total of 28 days

400mg vorinostat by mouth per day on days 8, 9,10 and days 22, 23, 24


Treatment: Drugs: Disulfiram, (National Drug Code) NDC 0378-4141-01
This study will provide open label disulfiram. Participants will take 2 grams (4x500mg tablets) of disulfiram per day for a total of 28 days

Treatment: Drugs: Vorinostat, NDC 00006-0568-40
This study will provide open label vorinostat. Participants will take 400mg (4x100mg capsules) of vorinostat per day on days 8, 9, 10 and days 22, 23, 24.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Day 11 Plasma HIV RNA Relative to Baseline
Timepoint [1] 0 0
Baseline and 11 days
Secondary outcome [1] 0 0
Incidence of Treatment-Emergent Adverse Events
Timepoint [1] 0 0
Adverse events were collected continuously throughout the study duration from day 1 on treatment until 2 months since last dose of study drug, an average duration of 3 months
Secondary outcome [2] 0 0
Plasma HIV RNA Relative to Baseline at Additional Time Points
Timepoint [2] 0 0
Baseline to Days 8, 15, 21, 38, 59, 196, 197. Data is reported for days where samples were collected for each participant.

Eligibility
Key inclusion criteria
* Age 18-65 years with documented HIV-1 infection (antibody positive or detectable plasma HIV-1 RNA)
* Receiving combination ART with plasma HIV RNA <50 copies/mL for >3 years
* CD4+ T cell count >350 microliter at screening
* Able to provide informed consent
* Willing to abstain from alcohol consumption from one day before to 14 days after completing 28 days of disulfiram
* One month post influenza vaccine (from screening visit)
* Women of non-child-bearing potential defined as > 12 months of spontaneous amenorrhea and = 45 years of age, or documented medical history of one of the following: hysterectomy, bilateral oophorectomy or tubal ligation.
* Women of Child Bearing Potential (WOCBP) with a negative pregnancy test at Screening and agrees to use one of the study protocol specified methods of contraception to avoid pregnancy
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Current alcohol use disorder or hazardous alcohol use (>7 drinks per week for women or > 14 drinks per week for men) as determined by clinical evaluation
* Current or recent (in the last 4 days) use of metronidazole or any drug formulation that contains alcohol or that might contain alcohol, including the gelatin capsule and liquid formulations of ritonavir, ritonavir/lopinavir, amprenavir and fosamprenavir, and alcohol-containing preparations such as cough syrups, tonics etc.
* Current use of tipranavir or Maraviroc
* Current use of zidovudine, stavudine or didanosine (as disulfiram potentially has potent irreversible inhibitory effects on mitochondrial metabolism and hence could exacerbate the toxicity of these drugs)
* Concurrent use of rivaroxaban (a CYP3A metabolized medication) as the cytochrome P450 inhibitory effects of disulfiram on rivaroxaban are unknown
* Current use of warfarin
* Individuals who intend to modify antiretroviral therapy during the study period for any reason
* Significant myocardial disease (current myocarditis or reduced left ventricular ejection fraction below the lower limit of normal) or diagnosed coronary artery disease
* Significant renal disease (eGFR <50 milliliter/minute)
* History of psychosis, seizure disorder, abnormal electroencephalogram or brain damage with significant persisting neurological deficit
* Prior malignancy active within the previous 3 years except for local curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the prostate, cervix or breast.
* Known hypersensitivity to disulfiram or vorinostat or contraindications to treatment with these agents
* Participation in another latency reversal study or receipt of vorinostat or disulfiram in the previous 12 months before starting the investigational treatment
* Any significant acute medical illness requiring hospitalization within preceding 8 weeks
* Hepatitis B (HBV) or hepatitis C (HCV) co-infection as determined by detection of HBsAg or HCV RNA (Individuals with prior hepatitis infection that is now cleared are eligible for enrolment)
* Receipt of immunomodulating agents (excluding immunization) or systemic chemotherapeutic agents within 28 days prior to study entry
* Current or recent gastrointestinal disease or surgery that may impact the absorption of the investigational drug
* Active substance use that in the opinion of the investigator will prevent adequate compliance with study procedures
* Women who are currently pregnant or breastfeeding
* Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy
* Unable or unwilling to adhere to protocol procedures
* The following laboratory values within 6 weeks before starting the investigational drug (lab tests may be repeated to obtain acceptable values before failure at screening is concluded)

* Hepatic transaminases (AST or ALT) =3 x upper limit of normal (ULN)
* Serum total bilirubin =1.5 x ULN
* eGFR <50 milliliter/min
* Hemoglobin <11.0 g/deciliter
* Platelet count =100 x10^9/L (liter)
* Absolute neutrophil count =1.5x10^9/L
* Serum potassium, magnesium, phosphorus outside normal limits
* Total calcium (corrected for serum albumin) or ionized calcium = lower normal limits

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/08/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/04/2019
Sample size
Target
Accrual to date
Final
5
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Department of Infectious Diseases, Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
University of Melbourne
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
The Alfred
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sharon R Lewin, FRACP, PhD
Address 0 0
The Doherty Institute, University of Melbourne
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No plan to share individual participant data


What supporting documents are/will be available?




Results publications and other study-related documents

TypeCitations or Other Details
Journal McMahon JH, Evans VA, Lau JSY, Symons J, Zerbato J... [More Details]


Results are available at https://clinicaltrials.gov/study/NCT03198559