First Time in Human Study of Long Acting VH4524184 Formulations

ViiV Healthcare

Status and phase: Enrolling; Phase 1

Conditions: HIV Infections

Treatments: Drug: Placebo Formulation A IM; Drug: Placebo Formulation B SC; Drug: VH4524184 Formulation B IM; Drug: Placebo Formulation B IM; Drug: VH4524184 Formulation B SC; Drug: Placebo Formulation C SC; Drug: rHuPH20; Drug: Oral VH4524184; Drug: Placebo Formulation A SC; Drug: VH4524184 Formulation A SC; Drug: VH4524184 Formulation C SC; Drug: VH4524184 Formulation A IM

Study type: Interventional

Funder types: Industry

Identifiers

NCT06310551

218804

Details and patient eligibility

About

The purpose of this study is to identify 1 or more doses of parenterally administered VH4524184 that are safe, well tolerated and yield a PK drug exposure profile necessary to deliver a long-acting antiretroviral therapy for the treatment of HIV-1 infection.

Enrollment: 72 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Age

1. Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent.

   Type of Participant and Characteristics

2. Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.

3. Participants who are negative for SARS-CoV-2, performed on admission/readmission to the Phase 1 unit, using an approved molecular test (PCR).

4. Participants who are able to understand and comply with protocol requirements and timetables, instructions, and protocol-stated restrictions.

   Weight

5. Body weight ≥50.0 kg (110 lbs) for men and ≥45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 32.0 kg/m2 (inclusive).

   Sex and Contraceptive/Barrier Requirements

6. Male or female

   1. Male Participants: No restrictions for male participants
   2. Participants of female sex assigned at birth is eligible to participate as long as the participant is not breastfeeding and is of non-childbearing potential.

   Informed Consent

7. Capable of providing signed informed consent.

Exclusion criteria

Medical Conditions

1. History or presence of clinical condition or disorder that could be capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study drug, interfering with the interpretation of data or would make the participant unsuitable for the study; unable to comply with dosing requirements; or unable to comply with study visits.

2. Abnormal blood pressure as determined by the investigator.

3. Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.

4. Breast cancer within the past 10 years.

5. Current or chronic history of liver disease or known hepatic or biliary abnormalities.

6. Medical history of cardiac arrhythmias or cardiac disease or a family and personal history of long QT syndrome.

7. Underlying skin disease or disorder that would interfere with the administration of study product and/or assessment of injection site reactions.

8. History of drug hypersensitivity, delayed-type hypersensitivity or severe hypersensitivity reactions, as well as history of /sensitivity to any of the study interventions including hyaluronidases.

9. Current or anticipated need for chronic anti-coagulation except for the use of low dose acetylsalicylic acid (≤325 mg) or hereditary coagulation and platelet disorders such as hemophilia or Von Willebrand Disease.

10. History of seizure.

11. Any known or suspected pre-existing psychiatric condition, including depression, anxiety and insomnia/sleep disturbances, at the discretion of the investigator.

12. Any positive (abnormal) response confirmed by the investigator or clinician (or qualified designee) administered C-SSRS at screening.

13. Insufficient muscle mass (gluteus medius or thigh) to support IM dose administration in the opinion of the investigator.

14. Presence of tattoos or skin piercings that may interfere with the administration of study product and/or assessment of ISRs, if they occur.

15. History of or on-going high-risk behaviors that may put the participant at increased risk for HIV acquisition in the opinion of the investigator. This includes participants in HIV discordant relationships, or men who report current or prior unprotected anal sex with other men and those reporting prior or current injecting drug use.

    Prior/Concomitant Therapy

16. Past or intended use of over-the-counter or prescription medication within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to dosing and for the duration of the study.

17. Receipt of any live vaccine(s) or vaccines against SARS-CoV-2 within 28 days prior to screening or 14 days before or after scheduled SC or IM dosing.

    Prior/Concurrent Clinical Study Experience

18. Exposure to more than 4 new investigational products (including long-acting investigational products) within 12 months prior to the first dosing day.

19. Current enrollment or past participation in another investigational study in which an investigational intervention was administered within the last 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product before signing of consent (OR screening) any other clinical study.

20. Participation in the study would result in loss of blood in excess of 500 mL over a 56-day period.

21. Current enrollment or past participation in this clinical study or prior participation in study 218803.

    Diagnostic Assessments

22. eGFR <60 mL/min or serum creatinine >1.1 x ULN.

23. Hemoglobin <12.5 g/dL for men and <11 g/dL for women

24. ALT or AST >1.5x upper limit of normal (ULN)

25. Total bilirubin >1.5xULN.

26. Any significant arrhythmia or ECG finding.

27. Exclusion criteria for Screening ECG - a single repeat is allowed for eligibility determination.

28. Presence of HBsAg at screening.

29. Positive Hepatitis C antibody test result at screening.

30. Positive pre-study drug/alcohol screen.

31. Positive HIV antibody test. Other Exclusions

32. Regular alcohol consumption within 6 months prior to the study defined as: An average weekly intake of >14 units for males or >7 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.

33. Regular use of known drugs of abuse.

34. Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening and at admission.

35. Sensitivity to the study drug, or components thereof, or other drug or other allergy that, in the opinion of the investigator or Sponsor Medical Monitor, contraindicates participation in the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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72 participants in 6 patient groups

Formulation A SC Group

Experimental group

Description:

Participants receive a Formulation A starting dose of VH4524184 LAI subcutaneously (SC).

Treatment:

Drug: rHuPH20

Drug: VH4524184 Formulation A SC

Drug: Placebo Formulation A SC

Drug: Oral VH4524184

Formulation B SC Group

Experimental group

Description:

Participants receive a Formulation B starting dose of VH4524184 LAI subcutaneously.

Treatment:

Drug: rHuPH20

Drug: VH4524184 Formulation B SC

Drug: Placebo Formulation B SC

Drug: Oral VH4524184

Formulation C SC Group

Experimental group

Description:

Participants receive a Formulation C starting dose of VH4524184 LAI subcutaneously. This intervention is optional and initiated only if Formulation B is poorly tolerated.

Treatment:

Drug: Placebo Formulation C SC

Drug: rHuPH20

Drug: VH4524184 Formulation C SC

Drug: Oral VH4524184

Formulation A IM Group

Experimental group

Description:

Participants receive a Formulation A starting dose of VH4524184 LAI intramuscularly (IM).

Treatment:

Drug: VH4524184 Formulation A IM

Drug: Placebo Formulation A IM

Drug: Oral VH4524184

Formulation B IM Group

Experimental group

Description:

Participants receive a Formulation B starting dose of VH4524184 LAI intramuscularly (IM).

Treatment:

Drug: Placebo Formulation B IM

Drug: VH4524184 Formulation B IM

Drug: Oral VH4524184

Multiple doses Group

Experimental group

Description:

VH4524184 LAI formulations administered SC or IM as single doses that achieve adequate PK exposure targets, may be evaluated for safety and tolerability as multiple doses.

Treatment:

Drug: Placebo Formulation C SC

Drug: rHuPH20

Drug: VH4524184 Formulation A IM

Drug: VH4524184 Formulation C SC

Drug: VH4524184 Formulation B SC

Drug: VH4524184 Formulation A SC

Drug: Placebo Formulation B IM

Drug: VH4524184 Formulation B IM

Drug: Placebo Formulation A SC

Drug: Placebo Formulation B SC

Drug: Placebo Formulation A IM

Drug: Oral VH4524184