Safety and Efficacy of Fixed Dose Combination Dolutegravir/Abacavir/Lamivudine FDC Initiated During Acute HIV Infection

• Status: Completed
• Trial end date: 2021-08-11
• Target enrollment: 0
• Participant gender: All

Summary

This is a multicenter, single arm, 96-week open-label study of the safety and virologic efficacy of fixed dose combination Dolutegravir/Lamivudine/Abacavir (DTG/3TC/ABC FDC) initiated during acute HIV infection (AHI).

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cynthia L Gay, MD; University of North Carolina, Chapel Hill
• Collaborators: National Cancer Institute (NCI); ViiV Healthcare
• Treatments: Abacavir; Dideoxynucleosides; Dolutegravir; Lamivudine

Criteria

Inclusion Criteria

1. Documentation of Acute HIV infection at or within 30 days of study entry.

2. Men and women age ≥18 years.

3. ART naive, defined as ≤14 days of antiretroviral treatment at any time prior to entry. The only exceptions are:

• Pre-exposure prophylaxis (PrEP) and documented as HIV-1 negative at least 1 month prior to AHI diagnosis during PrEP, and

• Post-exposure prophylaxis (PEP) provided the participant was documented as HIV-1 negative at least 3-6 months following completion of PEP treatment.

4. Lab values obtained within 30 days prior to study entry:

• Absolute neutrophil count >500/mm3

• Hemoglobin > 8.5 g/dL for men and > 8.0 g/dL for women

• Platelet count >50,000/mm3

• Lipase ≤ 3 X upper limit of normal (ULN), single repeat test is allowed to determine eligibility

• Calculated creatinine clearance (Cockcroft-Gault formula) ≥ 50mL/min:

CrCl = (140-age) x body weight (kg) (x 0.85 if female) Serum creatinine [mg/dL] x (72)

5. Testing for HBsAg is pending. Note: Participants who test positive for HBsAg will be terminated from the study prior to starting study treatment.

6. Testing for HLA-B57 and/or HLA-B*5701 is pending. Note: Participants who test positive for HLA-B*5701 will be terminated from the study prior to starting study treatment.

7. A female is eligible to enter and participate in the study if she:

• Is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy; or,

• Is of child-bearing potential, with a negative pregnancy test at screening and at enrollment, who agrees to use one of the methods of contraception listed below.

• Complete abstinence from intercourse from 2 weeks prior to administration of study medication, throughout the study, and for at least 2 weeks after discontinuation of all study medication;

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

• Approved hormonal contraception - used alone is not considered a sufficient form of contraception for the study see Protocol Appendix 1 for a listing of examples of approved hormonal contraception;

• Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year; see Protocol Appendix 2 for a listing of IUDs meeting this criterion;

• Male partner sterilization confirmed prior to the female participant's entry into the study, and this male is the sole partner for that patient;

• Any other method with published data showing that the expected failure rate is <1% per year.

• Any contraception method must be used consistently, in accordance with the approved product label and for at least 2 weeks after discontinuation of the study medication.

8. Females who meet the post-menopausal definition, noted in inclusion criterion 7, will have a follicle stimulation hormone (FSH) test to verify menopause,

9. Ability and willingness of participant to give written informed consent.

Exclusion Criteria

1. ALT ≥ 5 times Upper Limit of Normal (≥5xULN)

2. AST ≥ 3x ULN

3. Bilirubin ≥1.5x ULN (with >35% direct bilirubin)

4. Weight <40 kg

5. Women who are breast-feeding.

6. Women with a positive pregnancy test on enrollment or prior to study drug administration.

7. Women and men of child bearing potential unwilling to agree to use an effective methods of contraception required by the study.

8. History or presence of allergy to the study drugs or their components.

9. Requires or is anticipated to require any of the prohibited concomitant therapy:

barbiturates, dofetilide, fampridine (dalfampridine), modafinil, oxcarbazepine, pioglitazone, pilsicainide, pimozide, rifampin, rifapentine, phenytoin, phenobarbital, carbamazepine, and St. John's wort.

• Dofetilide, fampridine, and pilsicainide are prohibited, as DTG may inhibit its renal tubular secretion resulting in increased dofetilide concentrations and potential for toxicity.

10. Unable to discontinue any current medications that are excluded during study treatment.

11. Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), radiation therapy, HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry.

• Prednisone at a daily dose of 10 mg or less (physiologic replacement dose) is permitted.

12. Treatment with radiation therapy or cytotoxic chemotherapeutics agents within 28 days prior to screening or has an anticipated need for these agents during the study.

13. Administration of an HIV-1 immunotherapeutic vaccine within 90 days prior to screening.

14. Prior treatment with any other experimental drug for any indication (within 30 days of initiating study treatment).

15. Difficulty swallowing capsules/tablets.

16. Inability to communicate effectively with study personnel.

17. Incarceration; prisoner recruitment and participation are not permitted.

18. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements or confound the analysis of study endpoints.

19. Any condition (including but not limited to alcohol and drug use) or any active clinically significant disease or findings during screening of medical history or physical examination, which, in the opinion of the Investigator would interfere with patient safety or compliance.

20. Serious illness requiring systemic treatment and/or hospitalization until patient either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry.

NOTE: Oral candidiasis, vaginal candidiasis, mucocutaneous herpes simplex, and other minor illnesses (as judged by the site investigator) have no restriction.

21. A life expectancy less than twelve months.

22. Acute viral hepatitis, including, but not limited to, hepatitis A, B, or C.

23. History of myocardial infarction or diagnosis of coronary artery disease.

24. History of ongoing or clinically relevant pancreatitis within the previous 6 months.

25. Chronic hepatitis C infection with an anticipated need for treatment during the study period (through week 96).

26. Chronic hepatitis B infection (see inclusion criterion 5).

27. Evidence for moderate to severe hepatic impairment (as defined by the presence of cirrhosis, ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice or Child-Pugh class B or greater hepatic impairment).

28. Evidence of biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

29. Any verified grade 4 laboratory abnormality with exception of ALT as defined in exclusion criterion 1