Dolutegravir-Lamivudine as Dual Therapy in Naive HIV-Infected Patients: A Pilot Study

HIV-1 Infection Clinical Trial

— PADDLE  

Official title:

Dolutegravir-Lamivudine as Dual Therapy in Naive HIV-Infected Patients: A Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02211482
• Other study ID #: FH-18
• Status: Completed
• Phase: Phase 4
• First received: August 5, 2014
• Last updated: August 10, 2017
• Start date: October 2014
• Est. completion date: April 2017

Study information

• Verified date: August 2017
• Source: The Huesped Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the antiviral efficacy, safety and tolerability of dual therapy with 3TC and DTG as initial therapy among naïve HIV patients

Description:

The purpose of this study is to compare the antiviral efficacy, safety and tolerability of dual therapy with 3TC and DTG as initial therapy among naïve HIV patients.

Data collected in this study would inform the development of larger studies designed to evaluate metabolic and long term safety, impact on inflammatory biomarkers, efficacy, safety and cost effectiveness of this strategy among naïve and suppressed patients.

Primary endpoint:Proportion of patients with HIV-1 RNA levels of less than 50 copies/mL at week 48.

Secondary endpoints: Frequency, type and severity of adverse events and laboratory abnormalities, Proportion of patients with HIV-1 RNA <1000 copies/mL at week 12, Proportion of patients with HIV-RNA <400 at week 24 Number and type of resistance mutations in case of virologic failure (defined as a confirmed viral above 400 copies/mL after week 24 copies/mL or viral rebound at any timepoint) Changes in CD4+ lymphocyte count between baseline and 48 weeks, Estimation of the viral decay compared to historical data.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 2017
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. > 18 years of age

2. Documented HIV-1 infection (positive ELISA plus a confirmatory Western Blot; or plasma HIV-1 RNA =10,000 copies/mL)

3. Voluntarily signed and dated , IRB / IEC approved informed consent form

4. Agrees not to take any other medication during the study

5. Screening HIV RNA >5,000 copies/mL and = 100,000 copies/ml

6. Naïve to ARV therapies

7. CD4 =200 cells/mL

8. Subjects can comply with protocol requirements

9. Subject's general medical condition, in the investigator's opinion, does not interfere with assessments and completion of the trial

10. Patient is a male or a female not breastfeeding or pregnant

11. A female, may be eligible if she:

1. is of non-child-bearing potential

2. is of child-bearing potential with a negative pregnancy test at Screening and Day 1 and agrees to use one of the following methods:

• Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 2 weeks after

• Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide)

• IUD and male condom

• Male partner sterilization confirmed and male condom

• Approved hormonal contraception and male condom

• Any other method with published data showing that the expected failure rate is <1% per year and use male condom

• Any contraception method must be used for at least 2 weeks after discontinuation of IP

Exclusion Criteria:

1. Genotypic resistance to lamivudine at screening,as per IAS -USA Panel 2013 2. Alcohol or drug use that might impact on adherence 3. Subjects positive for Hepatitis B at screening (+HBsAg), or anticipated need for Hepatitis C virus (HCV) therapy during the study 4. Lactating, pregnancy or fertile women willing to be pregnant 5. Concomitant use of lowering lipid drugs, interferon, interleukin-2, cytotoxic chemotherapy, Dofetilide (or pilsicainide ) or immunosuppressors at study entry 6. Grade 4 lab abnormalities 7. Primary HIV infection (indeterminate WB or previous negative HIV in the last 6 months.) 8. Opportunistic infection (CDC C category) or other disease and/or clinical condition that, in the investigator's opinion, would compromise the patient's safety or outcome of the study; including malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia 9. Subjects who in the investigator's judgment, poses a significant suicidality risk 10. History or presence of allergy to the study drugs or their components or drugs of their class 11. Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; any immunomodulators that alter immune responses or treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening or exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of investigational product 12. Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the subject's participation in the study of an investigational compound 13. Alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN), or ALT = 3xULN and bilirubin = 1.5xULN (with >35% direct bilirubin) 14. Creatinine clearance of <50 mL/min via Cockcroft-Gault method 15. Subjects with moderate to severe hepatic impairment (Class B or greater) as determined by Child-Pugh classification

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• dolutegravir, lamivudine
single arm

Locations

Country	Name	City	State
Argentina	Fundacion Huesped	Caba	Buenos Aires

Sponsors (2)

Lead Sponsor	Collaborator
The Huesped Foundation	ViiV Healthcare

Country where clinical trial is conducted

Argentina, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	efficacy	Proportion of patients with HIV-RNA <400 at week 24	24 weeks
Other	safety	change in lipid profile between baseline and week 48.	48 weeks
Other	efficacy	Proportion of patients with HIV-1 RNA <1000 copies/mL at week 12	12 weeks
Other	Number and type of resistance mutations in case of virologic failure (defined as a confirmed viral above 400 copies/mL after week 24 copies/mL or viral rebound at any timepoint)	Number and type of resistance mutations in case of virologic failure (defined as a confirmed viral above 400 copies/mL after week 24 copies/mL or viral rebound at any timepoint)	48 weeks
Other	efficacy	Changes in CD4+ lymphocyte count between baseline and 48 weeks	48 weeks
Primary	Efficacy Outcome Measure	Percentage of Participants with HIV-1 RNA levels of less than 50 copies/mL at week 48 by ITT analysis	48 weeks
Secondary	safety	Frequency, type and severity of adverse events and laboratory abnormalities	48 week