Impact of Recombinant Human Growth Hormone on HIV Persistence

• Status: Unknown status
• Trial end date: 2020-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Antiretroviral therapy (ART) has improved the health of more than 18 million people infected with HIV by controlling viral replication, AIDS and non-AIDS events, and by reducing the risk of transmission. However, the existence of latent viral reservoirs in long-lived memory CD4 T cells remains a hurdle to curing HIV infection; consequently patients must remain on ART for the rest of their lives. Recently, a more realistic approach under limelight is to identify strategies leading to a functional cure, which is defined as the natural control of viral reservoir by the host. Use of recombinant human growth hormone has been shown to improve immune function by several mechanisms. This study hypothesizes that treatment with recombinant human growth hormone will decrease the size of the replication competent HIV reservoir in HIV-infected immune-reconstituted individuals.

The specific study objectives include:

• To evaluate the effect of recombinant human growth hormone administration for 48 weeks on the size of the replication competent HIV reservoir

• To evaluate the safety and tolerability of recombinant human growth hormone administration for 48 weeks in HIV-infected individuals on suppressive ART.

For this purpose, the investigators will add recombinant human growth hormone treatment for the patients receiving stable ART. Approximately 22 participants will be enrolled in this study at the Chronic Viral Illness Service of the McGill University Health Centre (Montreal, Canada), which will last about 52 weeks. Participants will be treated with recombinant human growth hormone for a total of 48 weeks. The initial recombinant human growth hormone dose will be 3 mg/day (30-40 µg/kg/d) for 24 weeks administered by subcutaneous injection on an outpatient basis, followed by dose reduction to 1.5 mg/day for the final 24 weeks of the treatment period, also conducted on an outpatient basis. The study inclusion criteria include male and female participants, ≥18 and <40 years of age, with an undetectable viral load (the quantity of the HIV virus in the blood must be less than 50 copies/ml) during last 24 months and with a CD4 T-cell count ≥350 cells/mm3 obtained within 30 days prior to study entry. The findings from this study will contribute to the development of novel strategies to eradicate HIV.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborator: EMD Serono
• Treatments: Hormones

Criteria

Inclusion Criteria:

• HIV-1 infected male or female adults aged ≥18 and <40 years

• Able to provide written consent

• Currently on continuous ART for at least 24 months with no change in regimen in 12 weeks prior to study entry. Some modifications of ART doses during the 12 weeks prior to study entry are permitted. In addition, the change in formulation (e.g., from standard formulation to fixed-dose combination) is allowed within 12 weeks prior to study entry. A within class single drug substitution (e.g., switch from tenofovir to abacavir or raltegravir to dolutegravir) is allowed within 12 weeks prior to study entry

• CD4+ T-cell count ≥350 cells/mm3 obtained within 30 days prior to study entry.

• HIV-1 RNA level below the limit of quantification using an FDA-approved assay for at least 24 months prior to study entry and confirmed within 60 days prior to study entry. Single determinations that are between the assay quantification limit and 200 copies/mL are allowed as long as the preceding and subsequent determinations are below the level of quantification

• Female participants, may be eligible to enter and participate in the study if they are: of non-child-bearing potential (defined as physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy), or of child- bearing potential with a negative pregnancy test at both Screening and Day 1 and agree to use one of the following methods of contraception to avoid pregnancy:

1. Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 2 weeks after discontinuation of all study medications

2. Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide); barrier methods must be in use at least 14 days prior to study drug administration

3. Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs meet this criterion. IUD must be in use at least 30 days prior to first study drug administration

4. Male partner sterilization confirmed prior to the female subject's entry into the study, and this male is the sole partner for that subject; the vasectomy must be completed 3 months prior to first study drug administration or in the alternative that a 0 sperm count will suffice

5. Approved hormonal contraception

6. Any other method with published data showing that the expected failure rate is <1% per year Note: Any contraception method must be used consistently, in accordance with the approved product label and for at least 2 weeks after discontinuation of recombinant human growth hormone.

Exclusion Criteria:

• Fasting glucose ≥100 mg/dL

• Hemoglobin A1c ≥ 5.7%

• ALT [serum glutamic pyruvic transaminase (SGPT)] > 2 times upper limit of normal (ULN)

• AST [serum glutamic oxaloacetic transaminase (SGOT)] > 2 x ULN

• Estimated creatinine clearance ≤ 50 mL/min by Cockcroft-Gault

• Hemoglobin < 11.5 g/dL

• Platelets <100,000/mm3

• ANC < 1000/mm3

• Any active or past history of malignancy, except for localized cutaneous Kaposi's sarcoma (fewer than 10 lesions, none of which are larger than 2 cm, and not on active therapy)

• Prior therapy with growth hormone or tesamorelin during 12 months preceding screening visit

• Unstable or untreated hypertension, defined as ≥ 160/90 mm Hg at the time of the screening visit

• History of pancreatitis, carpal tunnel syndrome (unless resolved by surgical release), diabetes mellitus, angina pectoris, coronary artery disease, or any disorder associated with moderate to severe edema (e.g. ascites, nephrotic syndrome, congestive heart failure, lymphedema)

• Acute or serious illness requiring systemic treatment and/or hospitalization within 90 days prior to study entry

• Receipt of antibiotic therapy within 30 days prior to study entry

• Chronic hepatitis C infection defined as a positive hepatitis C antibody and positive hepatitis C RNA at any time prior to study entry. Subjects who are positive for hepatitis C antibody but who are HCV RNA negative are permitted in the study

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

• Known allergy/sensitivity or any hypersensitivity to components of study drug or their formulation

• Recent vaccination within 30 days prior to study entry or expected vaccination after screening but before baseline visit

• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements

• Receive testosterone therapy for hypogonadism unless prior testosterone deficiency is documented

• Change in regimen or supraphysiological dose of testosterone in men (measured by elevated free testosterone above normal levels) within 2 months prior to screening

• Use of anabolic steroids, GH, GH secretagogue, GHRF products or analogs, IGF-1, or IGF binding protein 3 (IGFBP 3) within 6 months prior to screening

• Women who are lactating