Early Administration of Romidepsin and 3BNC117 in Treatment-naïve HIV Patients Starting ART

Hiv Clinical Trial

— eCLEAR  

Official title:

Early Administration of Latency Reversing Therapy and Broadly Neutralizing Antibodies to Limit the Establishment of the HIV-1 Reservoir During Initiation of Antiretroviral Treatment - a Randomized Controlled Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03041012
• Other study ID #: eCLEAR-001
• Secondary ID: 2015-002234-53
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 20, 2017
• Est. completion date: December 30, 2021

Study information

• Verified date: April 2021
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the effect of early viral reactivation by latency reversing agents (LRA) and/or administration of potent broadly neutralizing antibodies (bNAb) on the size of the latent HIV-1 reservoir in treatment naïve HIV-1 patients initiating antiretroviral therapy (ART)

Description:

The study will be conducted among ART naïve HIV-1-infected patients.

Subjects will continue ART while receiving LRA romidepsin and/or bNAb 3BNC117.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: December 30, 2021
• Est. primary completion date: August 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documented HIV-1 infection

• CD4+ T cell count >200/µL on last visit prior to study entry

• ART naïve

• Able to give informed consent

Exclusion Criteria:

• Any significant acute medical illness (not including primary HIV infection) in the past 8 weeks

• Any evidence of an active AIDS-defining opportunistic infection

• Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy

• The following laboratory values at screening, but the values can be repeated within the screening period, but test results must be available before baseline (day 0) and checked for eligibility:

• Hepatic transaminases (AST or ALT) =3 x upper limit of normal (ULN)

• Serum total bilirubin =3 ULN

• Estimated glomerular filtration rate (eGFR) =60 mL/min (based on serum creatinine or other appropriate validated markers)

• Platelet count =100 x10^9/L

• Absolute neutrophil count =1x10^9/L

• Serum potassium, magnesium, phosphorus outside =1.5 ULN/LLN

• Total calcium (corrected for serum albumin) or ionized calcium =1.5 ULN/LLN

• Hepatitis B or C infection as indicated by the presence of hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood

• ECG at screening that shows QTc >450 ms when calculated using the Fridericia formula from either lead V3 or V4 [86]

• Use of:

• Warfarin or warfarin-derivatives

• HDACi

• An agent definitely or possibly associated with effects on QT intervals within 2 weeks of screening

• Drugs that induce or inhibit CYP3A4 or P-gp

• History of:

• Clinically significant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for Torsades de pointes (e.g. heart failure)

• Malignancy or transplantation, including skin cancers or Kaposi sarcoma

• Diabetes mellitus

• Receipt of strong immunosuppressive or systemic chemotherapeutic agents within 28 days prior to study entry

• Known resistance to >2 classes of ART

• Known hypersensitivity to the components of romidepsin, 3BNC117 or their analogues

• Women who are pregnant or breastfeeding, or with a positive pregnancy test during screening or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method of non-estrogen containing contraceptions (according to the Danish Medicines Agency guidelines) to avoid pregnancy for the 3 week study period and 4 weeks after study treatment or until undetectable plasma HIV-1 RNA using standard assays

• Males or females who are unwilling or unable to use barrier contraception during sexual intercourse for the 3-week study period, and 4 weeks after study treatment or until undetectable plasma HIV-1 RNA using standard assays

Related Conditions & MeSH terms

• Hiv

Intervention

Drug:
• Romidepsin
5mg/m2 romidepsin will be administered IV on days 10, 17, and 24 after initiating ART
• 3BNC117
30 mg/kg 3BNC117 will be administered IV on day 7 and 21 after initiating ART
• Antiretrovirals
Combination antiretroviral therapy

Locations

Country	Name	City	State
Denmark	Department of Infectious Diseases	Aalborg
Denmark	Dept. of Infectious Diseases, Aarhus University Hospital	Aarhus
Denmark	Department of Infectious Diseases	Hvidovre
Denmark	Department of Infectious Diseases	København
Denmark	Department of Infectious Diseases	Odense
United Kingdom	Guy's and St Thomas'	London
United Kingdom	Imperial College Healthcare NHS Trust	London

Sponsors (8)

Lead Sponsor	Collaborator
Aarhus University Hospital	Aalborg University Hospital, Hammersmith Hospitals NHS Trust, Herning Hospital, Hvidovre University Hospital, Odense University Hospital, Rigshospitalet, Denmark, St Mary's Hospital, London

Countries where clinical trial is conducted

Denmark,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Plasma cytokine and immune activation biomarker levels	Soluble IL-6, sCD14, sCD163	1 year
Primary	Plasma HIV RNA kinetics	Time to undetectable (<20 c/mL)	3 months
Primary	Quantification of the size of the proviral HIV reservoir	Copies of total HIV-1 DNA per 106 CD4+ T cells as measured by digital droplet PCR	1 year
Primary	Time to viral rebound during ATI	Days from stopping ART to plasma HIV RNA >5,000 on two consecutive measurements	12 weeks
Secondary	Incidence of treatment emerging events (Safety and tolerability)	Frequence and severity of adverse events (AE), adverse reactions (AR), serious adverse events (SAE), serious adverse reactions (SAR) and suspected unexpected serious adverse reactions (SUSAR).	1 year
Secondary	Quantification of the intact proviral DNA	Intact HIV-1 DNA in CD4+ T cells (copies per million cells) as measured by dd-PCR.	1 year
Secondary	Quantification of HIV mRNA and/or p24 positive cells	Frequency of mRNA/p24 postive per 1 million CD4+ T cells by FISH-flow	30 days from study entry
Secondary	Immune reconstitution	Absolute CD4+ and CD8+ T cell count	1 year
Secondary	Analytic treatment interruption (ATI) study	Time to first plasma HIV RNA >5000 c/mL	64 weeks
Secondary	Impact of pre-ART virus sensitivity to 3BNC117 on ATI outcomes	3BNC117 sensitivity determined by PhenoSense and/or HIV env sequencing	Baseline and at viral rebound
Secondary	T cell mediated HIV specific immunity	T cell immunity as determined by the HIV AIM assay	First of 365 days