Phase II Safety and Acceptability of an Investigational Injectable Product, TMC278LA, for Pre-Exposure Prophylaxis

NCT02165202 | Completed Phase 2 Results DMC

• 3 other identifiers: HPTN 0761015131UM1AI068619
• Study Type: interventional
• Target: 136
• Locations: 3 countries
• Sites: 4

Brief Summary

This is a multi-site, double-blinded, two-arm, two:one, randomized, trial comparing the safety of an intramuscular (IM) injection of TMC278 LA to a placebo given once every eight weeks over a 40 week period among sexually active, HIV- uninfected women.

Conditions

Human Immunodeficiency Virus (HIV)

Keywords

HIV Pre-exposure Prophylaxis;; long-acting injectable;; HIV PrEP;; biomedical HIV prevention research

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing Any Grade 2 or Higher AEs During Injection Phase

  Number of participants experiencing any Grade 2 or higher clinical and laboratory AEs to evaluate the safety of the injectable product, TMC278 LA (1200 mg dose administered at Weeks 4, 12, 20, 28, 36 and 44), through 48 weeks after initial injection (at Week 52) in women in SSA and the US.

  Up to 52 weeks

Study Arms (2)

Rilpivirine

ACTIVE COMPARATOR

Arm 1: Participants randomized to the active arm will receive rilpivirine 25 mg capsules once daily for four weeks to be taken orally with a meal. Participants will then receive IM injections of TMC278 LA, 1200 mg dose, at eight week intervals (at Weeks 4, 12, 20, 28, 36 and 44). On each dosing occasion 1200 mg of TMC278 LA will be delivered in two, 2 mL injections, one in each gluteus maximus muscle. All participants will receive a total of six doses (12 IM injections).

Drug: Rilpivirine

Placebo

PLACEBO COMPARATOR

Arm 2: Participants randomized to the placebo arm will receive placebo capsules once daily for four weeks to be taken orally with a meal. Participants will then receive IM injections of saline (0.9% NaCI) at eight week intervals (at Weeks 4, 12, 20, 28, 36 and 44). On each dosing occasion placebo will be delivered in two, 2 mL injections, one in each gluteus maximus muscle. All participants will receive a total of six doses (12 IM injections).

Drug: Placebo

Interventions

Rilpivirine DRUG

Rilpivirine (TMC278), a non-nucleoside reverse transcriptase inhibitor (NNRTI) is a substituted diaryl-pyrimidine (DAPY) derivative with potent antiviral activity against HIV. It is approved by the US FDA for once daily oral administration and is effective as part of treatment for ARV-na'ive HIV-infected patients as rilpivirine 25 mg capsules. It is also co-formulated with TDF and FTC for use as a once- daily single fixed-dose combination (Complera™).

Rilpivirine

Placebo DRUG

Participants randomized to the placebo arm will receive oral placebo capsules prior to injection of saline solution (0.9%NaCI). Participants will be observed while taking the study product by site staff on approximately six occasions during the first two weeks of the oral run-in at Week 0 (Enrollment), at Week 2 (Oral Run-in Safety Visit), and on four separate DOT visits between Weeks 0 and 2. Cervicovaginal and rectal fluid will be collected for PK studies at a single follow-up visit.

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women, 18- 45 years (inclusive) of age at Enrollment
• Female at birth
• Willing and able to provide informed consent to take part in the study
• Willing and able to provide adequate locator information
• Willing and able to provide acceptability and adherence assessments throughout the study
• Understands and agrees to local reporting requirements for sexually transmitted infections (STis)
• No evidence of an active STI, women who have an STI (Chlamydia trachomatis (CT), Neisseria gonorrhoeae (GC), or syphilis) identified at the Screening visit are ineligible\*
• Per participant report, no diagnosis of GC, CT, or syphilis in the last 6 months
• Availability to return for all study visits and participate in all study-related procedures, barring unforeseen circumstances
• Per participant report, using (or willing to use) an acceptable form of contraception (e.g., intrauterine device \[IUD\], hormonal contraception \[DMPA\], oral, injectable, transdermal patch, implants) from screening until one month after last study visit or surgical sterilization of the participant
• Must agree to use condoms for the duration of the study
• Must agree not to participate in other concurrent drug or vaccine trials
• Normal laboratory values\*\*
• (HIV tests performed at Screening and Enrollment are non- reactive/negative (see Study Specific Procedures (SSP) Manual)
• Hemoglobin (women) =:: 10.5 g/dL

You may not qualify if:

• Experiencing early menopause using clinical criteria (amenorrhea greater than six months in absence of pregnancy) or a prior report of an abnormal Follicle Stimulating Hormone (FSH) test
• PrEP or post-exposure prophylaxis (PEP) for HIV exposure within 90 days prior to Screening
• Pregnant or last pregnancy outcome 90 days or less prior to Screening
• Currently breastfeeding
• Intends to become pregnant during the period of study participation
• Experiencing uncontrolled depression or active suicidal ideation
• History of recurrent urticaria
• Any history of anaphylaxis or severe allergy resulting in angioedema
• Any serious acute, chronic, or progressive disease (e.g. known history of neoplasm, cancer, insulin-dependent diabetes, cardiac disease, auto-immune disease), or with signs of cardiac disease, renal failure, or severe malnutrition
• Any laboratory abnormalities that are Grade 2 or higher, according to the DAIDS Toxicology tables (please see Section 6.1 for a list of Screening laboratory tests)
• Recreational injection drug use in the 52 weeks prior to screening
• Participating or plans to participate in another research study involving study drugs, vaccines or medical devices
• Participated in another research study involving study drugs, vaccines or medical devices within the four weeks prior to screening; may be longer than four weeks depending on half-life of study drug
• Past participation in an HIV vaccine study
• Has plans to relocate and cannot attend the visits at the clinic

Sponsors & Collaborators

• PATH: lead
• Bill and Melinda Gates Foundation: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (4)

New Jersey Medical School Clinical Research Center

Newark, New Jersey, 07103, United States

Location

Bronx Prevention Center

The Bronx, New York, 10451, United States

Location

Emavundleni Clinical Research Site

Cape Town, South Africa

Location

Spilhaus Clinical Research Site

Belgravia, Harare, Zimbabwe

Location

Related Publications (12)

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• Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, Goicochea P, Casapia M, Guanira-Carranza JV, Ramirez-Cardich ME, Montoya-Herrera O, Fernandez T, Veloso VG, Buchbinder SP, Chariyalertsak S, Schechter M, Bekker LG, Mayer KH, Kallas EG, Amico KR, Mulligan K, Bushman LR, Hance RJ, Ganoza C, Defechereux P, Postle B, Wang F, McConnell JJ, Zheng JH, Lee J, Rooney JF, Jaffe HS, Martinez AI, Burns DN, Glidden DV; iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010 Dec 30;363(27):2587-99. doi: 10.1056/NEJMoa1011205. Epub 2010 Nov 23.

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• Seneviratne HK, Tillotson J, Lade JM, Bekker LG, Li S, Pathak S, Justman J, Mgodi N, Swaminathan S, Sista N, Farrior J, Richardson P, Hendrix CW, Bumpus NN. Metabolism of Long-Acting Rilpivirine After Intramuscular Injection: HIV Prevention Trials Network Study 076 (HPTN 076). AIDS Res Hum Retroviruses. 2021 Mar;37(3):173-183. doi: 10.1089/AID.2020.0155. Epub 2021 Jan 13.

  PMID: 33191765 DERIVED

• Tolley EE, Li S, Zangeneh SZ, Atujuna M, Musara P, Justman J, Pathak S, Bekker LG, Swaminathan S, Stanton J, Farrior J, Sista N. Acceptability of a long-acting injectable HIV prevention product among US and African women: findings from a phase 2 clinical Trial (HPTN 076). J Int AIDS Soc. 2019 Oct;22(10):e25408. doi: 10.1002/jia2.25408.

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MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Rilpivirine

Condition Hierarchy (Ancestors)

HIV Infections; 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; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Heather Kelly
• Organization: PATH

hkelly@path.org

650-392-2510

Study Officials

• Jessica Justman, MD

  Bronx-Lebanon Hospital Center Clinical Research Site

  PRINCIPAL INVESTIGATOR

• Shobha Swaminathan, MD

  New Jersey Medical School Clinical Research Site

  PRINCIPAL INVESTIGATOR

• Zvavahera Michael Chirenje, MD, MSc

  Spilhaus Clinical Research Site

  PRINCIPAL INVESTIGATOR

• Linda-Gail Bekker, PhD

  The Desmond Tutu HIV Centre

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2014
• First Posted: June 17, 2014
• Study Start: October 1, 2014
• Primary Completion: April 13, 2015
• Study Completion: March 9, 2017
• Last Updated: August 27, 2018
• Results First Posted: July 26, 2018

Record last verified: 2018-07

Locations

ZI (1); ZA (1); US (2)