Evaluating BMD in Participants ≥50 Years Old Switching From EVG/COBI/FTC/TAF or EVG/COBI/FTC/TDF to ABC/DTG/3TC (STRUCTR)

• ClinicalTrials.gov Identifier: NCT03275701
• Recruitment Status: Unknown
• First Posted: September 7, 2017
• Last Update Posted: September 7, 2017
• Sponsor: Mills Clinical Research
• Collaborator: ViiV Healthcare
• Information provided by (Responsible Party): Anthony Mills MD, Mills Clinical Research

Study Description

Brief Summary:

Phase IV, Single-Arm, Open-Label Study Evaluating Bone Mineral Density in HIV-1-Infected Adults ≥50 Years Old Switching from EVG/COBI/FTC/TAF (Genvoya) or EVG/COBI/FTC/TDF (Stribild) to ABC/DTG/3TC (Triumeq)

Condition or disease	Intervention/treatment	Phase
Infection, Human Immunodeficiency Virus	Drug: Triumeq	Not Applicable

Detailed Description:

Phase IV, Single-Arm, Open-Label Study Evaluating Bone Mineral Density in HIV-1-Infected Adults ≥50 Years Old Switching from EVG/COBI/FTC/TAF (Genvoya) or EVG/COBI/FTC/TDF (Stribild) to ABC/DTG/3TC (Triumeq)

To evaluate the impact on BMD, as measured by DEXA over 48 weeks, of switching from an INSTI-based regimen with either TDF or TAF to a regimen of ABC/DTG/3TC (administered as commercial Triumeq) in chronic HIV-infected patients over the age of 50

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase IV, Single-Arm, Open-Label Study Evaluating Bone Mineral Density in HIV-1-Infected Adults ≥50 Years Old Switching From EVG/COBI/FTC/TAF (Genvoya) or EVG/COBI/FTC/TDF (Stribild) to ABC/DTG/3TC (Triumeq)
• Study Start Date: July 2016
• Estimated Primary Completion Date: October 2019
• Estimated Study Completion Date: November 2019

Arms and Interventions

Arm	Intervention/treatment
Triumeq; Single Arm, Open Label	Drug: Triumeq; Open Label, Switch to Triumeq (ABC/DTG/3TC)

Outcome Measures

Primary Outcome Measures :

1. Percent change from Baseline at Week 48 in total hip BMD (measured by DEXA) [ Time Frame: 48 Weeks ]
2. Percent change from Baseline at Week 48 in lumbar spine BMD (measured by DEXA) [ Time Frame: 48 Weeks ]

Other Outcome Measures:

1. Change from Baseline in bone biomarkers for individuals switching to ABC/DTG/3TC [ Time Frame: 96 Weeks ]
2. Change from baseline in bone mineral density (in lumbar spine and total hip) assessed by T-scores and Z-scores from Baseline in individuals switching to ABC/DTG/3TC [ Time Frame: 96 Weeks ]
   Z-score = (Patient's BMD - expected BMD) / SD; T-score = (BMD-Reference BMD)/SD Units are numerical in value. BMD)/SD Units are numerical in value.
3. Number of adverse events (including long-term virologic/immunologic responses, abnormal laboratory values, or untoward medical conditions) for individuals switching to ABC/DTG/3TC [ Time Frame: 96 Weeks ]

Eligibility Criteria

• Ages Eligible for Study: 50 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Documented HIV-1 infection;
2. At least 50 years of age;
3. Currently on a stable antiretroviral regimen (for ≥3 months preceding Screening) of either EVG/COBI/FTC/TAF (Genvoya) or EVG/COBI/FTC/TDF (Stribild);

4. HIV is currently suppressed, defined as:

   1. Plasma HIV-1 RNA <50 c/mL for ≥3 months preceding Screening; AND
   2. Plasma HIV-1 RNA <50 copies/mL at the Screening assessment; INCL 5. Documentation that the participant is negative for the human leukocyte antigen (HLA)-B*5701 allele.

Exclusion Criteria:

1. Pregnant, breastfeeding, or planning to become pregnant during the study period;
2. Bilateral hip replacement;
3. Exceeds weight limit for DEXA equipment (i.e., weighs >350 lbs or >159 kg);
4. History or presence of allergy to the study treatment (Triumeq) or any of its components (to ABC, DTG, or 3TC);
5. Active Centers for Disease Control and Prevention (CDC) Category C HIV-1 disease (see Section 17.1 for definition), with the exception of cutaneous Kaposi's sarcoma, not requiring systemic therapy and historic CD4+ cell counts of <200 cells/mm3;
6. Positive for hepatitis B virus surface antigen (HBsAg) at Screening;
7. Ongoing malignancies (other than localized malignancies, such as cutaneous Kaposi's sarcoma, basal cell carcinoma, cervical intraepithelial neoplasia);
8. Significant suicidal risk in the investigator's opinion;
9. Metabolic disease;
10. Treatment with HIV immunotherapeutic vaccine within 90 days of Screening;
11. Radiation, cytotoxic chemotherapy, or any immunomodulator (that alters immune responses) within 28 days of Screening;
12. Exposure to any experimental drug or vaccine within 28 days or 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to first dose of study treatment on Day 1;
13. History of use of only mono or dual NRTI therapy prior to starting combination ART for the treatment of HIV infection (except that prior NRTI use for the purpose of pre-exposure prophylaxis [PrEP] or postexposure prophylaxis [PEP] is not excluded);
14. Became HIV-positive (i.e., had a detectable plasma HIV-1 viral load) while taking PrEP or PEP;

15. Documented resistance to any component of the study treatment (ABC, DTG, or 3TC) as indicated by either:

    1. Historical genotype in the participant's medical record; OR
    2. Genotype obtained by GenoSure Archive evaluation at Screening;
16. Any verified screening Grade 4 laboratory abnormality that in the investigator's opinion is clinically significant;
17. Moderate to severe hepatic impairment (Class B or greater) as determined by Child-Pugh classification;

18. Either of the following liver chemistry elevations:

    1. Alanine amintotransferase (ALT) ≥5 x the upper limit of normal (ULN); OR
    2. ALT ≥3 x ULN and bilirubin ≥1.5 x ULN (with >35% direct bilirubin);
19. Creatinine clearance (CrCl) of <50 mL/min (calculated by CockroftGault equation)
20. QT interval corrected for heart rate according to Bazett's formula (QTcB) ≥450 msec or QTcB ≥480 msec for participants with bundle branch block;
21. Any other condition or substance use that in the opinion of the investigator places the participants at undue risk from participation in the study or that may negatively impact the integrity of the study analyses.

Contacts and Locations

Contacts

Contact: Anthony Mills, MD; 310-550-2271; tony.mills@millsclinicalresearch.com

Contact: Ron Knight; 310-550-2271; ron.knight@millsclinicalresearch.com

Locations

United States, California

Mills Clinical Research; Recruiting

Los Angeles, California, United States, 90069

Contact: Ron Knight 310-550-2271 ron.knight@millsclinicalresearch.com

Contact: Jake Collins 310-550-2271 jake.collins@millsclinicalresearch.com

Sponsors and Collaborators

Mills Clinical Research

ViiV Healthcare

Investigators

• Principal Investigator: Anthony M Mills, MD; Mills Clinical Research

More Information

• Responsible Party: Anthony Mills MD, Clinical Research Director, Mills Clinical Research
• ClinicalTrials.gov Identifier: NCT03275701
• Other Study ID Numbers: 205773
• First Posted: September 7, 2017
• Last Update Posted: September 7, 2017
• Last Verified: September 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Additional relevant MeSH terms:

Acquired Immunodeficiency Syndrome; HIV Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Triumeq; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents