Study to Evaluate Safety, Pharmacokinetics, and Antiviral Activity of Lenacapavir Administered Subcutaneously in Human Immunodeficiency Virus (HIV) -1 Infected Adults

NCT ID: NCT03739866

Last Updated: 2021-04-09

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

53 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-11-26

Study Completion Date

2020-06-15

Brief Summary

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The primary objectives of this study are:

Part A: To evaluate the short-term antiviral activity of lenacapavir (formerly GS-6207) with respect to the maximum reduction of plasma HIV-1 RNA (log10 copies/mL) from Day 1 through Day 10 compared to placebo in HIV-1 infected adults who are antiretroviral treatment naive or are experienced but capsid inhibitor (CAI) naive.

Part B: To evaluate the short-term antiviral activity of tenofovir alafenamide (TAF) with respect to the maximum reduction of plasma HIV-1 RNA (log10 copies/mL) from Day 1 through Day 10 in HIV-1 infected adult subjects who are antiretroviral treatment naïve or are experienced but without resistance to TAF.

Detailed Description

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Conditions

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HIV-1 Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Part A: Lenacapavir 20 mg

Participants will receive single dose of lenacapavir 20 mg on Day 1 followed by bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) as per standard-care therapy starting on Day 10 through Day 225.

Group Type EXPERIMENTAL

Lenacapavir

Intervention Type DRUG

Administered subcutaneously in the abdomen

B/F/TAF

Intervention Type DRUG

50/200/25 mg tablets administered orally once daily

Part A: Lenacapavir 50 mg

Participants will receive single dose of lenacapavir 50 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.

Group Type EXPERIMENTAL

Lenacapavir

Intervention Type DRUG

Administered subcutaneously in the abdomen

B/F/TAF

Intervention Type DRUG

50/200/25 mg tablets administered orally once daily

Part A: Lenacapavir 150 mg

Participants will receive single dose of lenacapavir 150 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.

Group Type EXPERIMENTAL

Lenacapavir

Intervention Type DRUG

Administered subcutaneously in the abdomen

B/F/TAF

Intervention Type DRUG

50/200/25 mg tablets administered orally once daily

Part A: Lenacapavir 450 mg

Participants will receive single dose of lenacapavir 450 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.

Group Type EXPERIMENTAL

Lenacapavir

Intervention Type DRUG

Administered subcutaneously in the abdomen

B/F/TAF

Intervention Type DRUG

50/200/25 mg tablets administered orally once daily

Part A: Lenacapavir 750 mg

Participants will receive single dose of lenacapavir 750 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.

Group Type EXPERIMENTAL

Lenacapavir

Intervention Type DRUG

Administered subcutaneously in the abdomen

B/F/TAF

Intervention Type DRUG

50/200/25 mg tablets administered orally once daily

Part A: Placebo

Participants will receive single dose of placebo matched to lenacapavir on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Administered subcutaneously in the abdomen

B/F/TAF

Intervention Type DRUG

50/200/25 mg tablets administered orally once daily

Part B: TAF 200 mg

Participants will receive a single dose of TAF 200 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.

Group Type EXPERIMENTAL

B/F/TAF

Intervention Type DRUG

50/200/25 mg tablets administered orally once daily

TAF

Intervention Type DRUG

Tablets administered orally

Part B: TAF 600 mg

Participants will receive a single dose of TAF 600 mg on Day 1 followed by B/F/TAF as per standard-care therapy starting on Day 10 through Day 225.

Group Type EXPERIMENTAL

B/F/TAF

Intervention Type DRUG

50/200/25 mg tablets administered orally once daily

TAF

Intervention Type DRUG

Tablets administered orally

Interventions

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Lenacapavir

Administered subcutaneously in the abdomen

Intervention Type DRUG

Placebo

Administered subcutaneously in the abdomen

Intervention Type DRUG

B/F/TAF

50/200/25 mg tablets administered orally once daily

Intervention Type DRUG

TAF

Tablets administered orally

Intervention Type DRUG

Other Intervention Names

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GS-6207 Biktarvy®

Eligibility Criteria

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Inclusion Criteria

* Plasma HIV-1 RNA ≥ 5,000 copies/mL but ≤ 400,000 copies/mL and CD4+ cell count \> 200 cells/mm\^3
* Treatment naive or experienced but CAI (for Part A only) and integrase strand transfer inhibitor (INSTI) naïve, and have not received any antiretroviral therapy (ART) within 12 weeks of screening
* Screening genotype report must show sensitivity to B/F/TAF to allow its initiation on Day 10
* Screening genotype report must show sensitivity to at least one agent in either non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) class to allow its use as part of standard of care oral antiretroviral treatment in the future
* Have adequate renal function (estimated glomerular filtration rate ≥ 70 mL/min)
* No clinically significant abnormalities in electrocardiography (ECG) at Screening
* Willing to initiate B/F/TAF on Day 10 after completion of all assessments

Exclusion Criteria

* Pregnant or lactating females
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Ruane Clinical Research Group, Inc.

Los Angeles, California, United States

Site Status

Mills Clinical Research

Los Angeles, California, United States

Site Status

One Community

Sacramento, California, United States

Site Status

The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Center

Torrance, California, United States

Site Status

Midway Immunology and Research Center

Ft. Pierce, Florida, United States

Site Status

Orlando Immunology Center PA

Orlando, Florida, United States

Site Status

Triple O Research Institute, P.A.

West Palm Beach, Florida, United States

Site Status

Be Well Medical Center

Berkley, Michigan, United States

Site Status

AIDS Arms, Inc., DBA Prism Health North Texas

Dallas, Texas, United States

Site Status

North Texas Infectious Diseases Consultants, P.A.

Dallas, Texas, United States

Site Status

Tarrant County Infectious Disease Associates

Fort Worth, Texas, United States

Site Status

The Crofoot Research Center, INC (dba Gordon E. Crofoot MD PA)

Houston, Texas, United States

Site Status

Countries

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United States

References

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Daar ES, McDonald C, Crofoot G, Ruane P, Sinclair G, Begley R, et al. Dose-response relationship of subcutaneous long-acting HIV capsid inhibitor GS-6207 [Poster]. Presented at: Conference on Retroviruses and Opportunistic Infections; 2020 March 8-11; Boston, MA, USA

Reference Type RESULT

Daar ES, McDonald C, Crofoot G, Ruane P, Sinclair G, Patel H, et al. Single doses of long acting capsid inhibitor GS-6207 administered by subcutaneous injection are safe and efficacious in people living with HIV [Poster]. Presented at: 17th European AIDS Conference; 2019 November 6-9; Basel, Switzerland.

Reference Type RESULT

Daar ES, McDonald C, Crofoot G, Ruane P, Sinclair G, Patel H, et al. Safety and antiviral activity over 10 days following a single dose of subcutaneous GS-6207, a first-in-class, long acting HIV capsid inhibitor in people living with HIV [Poster]. Presented at: 10th IAS Conference on HIV Science; 2019 21-24 July; Mexico City, Mexico.

Reference Type RESULT

Link JO, Rhee MS, Tse WC, Zheng J, Somoza JR, Rowe W, Begley R, Chiu A, Mulato A, Hansen D, Singer E, Tsai LK, Bam RA, Chou CH, Canales E, Brizgys G, Zhang JR, Li J, Graupe M, Morganelli P, Liu Q, Wu Q, Halcomb RL, Saito RD, Schroeder SD, Lazerwith SE, Bondy S, Jin D, Hung M, Novikov N, Liu X, Villasenor AG, Cannizzaro CE, Hu EY, Anderson RL, Appleby TC, Lu B, Mwangi J, Liclican A, Niedziela-Majka A, Papalia GA, Wong MH, Leavitt SA, Xu Y, Koditek D, Stepan GJ, Yu H, Pagratis N, Clancy S, Ahmadyar S, Cai TZ, Sellers S, Wolckenhauer SA, Ling J, Callebaut C, Margot N, Ram RR, Liu YP, Hyland R, Sinclair GI, Ruane PJ, Crofoot GE, McDonald CK, Brainard DM, Lad L, Swaminathan S, Sundquist WI, Sakowicz R, Chester AE, Lee WE, Daar ES, Yant SR, Cihlar T. Clinical targeting of HIV capsid protein with a long-acting small molecule. Nature. 2020 Aug;584(7822):614-618. doi: 10.1038/s41586-020-2443-1. Epub 2020 Jul 1.

Reference Type RESULT
PMID: 32612233 (View on PubMed)

Margot N, Ram R, Parvangada P, Martin R, Hyland R, Rhee M, Callebaut C. Lenacapavir resistance analysis in a phase Ib clinical proof-of-concept study [oral]. Presented at: HIV Glasgow; 2020 October 5 - 8; Virtual.

Reference Type RESULT

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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GS-US-200-4072

Identifier Type: -

Identifier Source: org_study_id

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