Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

CC-11050 in Human Immunodeficiency Virus-1-Infected Adults With Suppressed Plasma Viremia on Antiretroviral Therapy (APHRODITE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier:
NCT02652546
First received: January 9, 2016
Last updated: May 16, 2017
Last verified: May 15, 2017
  Purpose

Background:

When there is a threat to the body, the immune system triggers inflammation. Too much inflammation can damage the body or cause painful symptoms. Some people with HIV feel sick after they start HIV drugs because their recovering immune systems cause too much inflammation. Or their immune systems can become activated all the time. This can cause serious health problems. Researchers want to test if the drug CC-11050 helps treat inflammation in people taking HIV drugs.

Objectives:

To test if CC-11050 is safe and well-tolerated for people with HIV who are taking HIV drugs. To see if it reduces inflammation.

Eligibility:

People ages 18 and older with HIV who have been on antiretroviral therapy for at least 1 year.

Design:

Participants will be screened with:

Medicine review

Physical exam and medical history

Blood and urine tests

Chest x-ray

Electrocardiogram (ECG): Soft electrodes on the skin record heart signals.

Participants will be randomly assigned to take capsules of either CC-11050 or a placebo. They will take the capsules every day for 12 weeks. They will continue to take their HIV drugs.

Participants will have a baseline visit within 2 months of screening. This includes:

Physical exam and medical history

Blood and urine tests

ECG

Leukapheresis: Blood is removed by a needle in one arm and passed through a machine that removes white blood cells. The rest of the blood is returned through a needle in the other arm.

Participants will have follow-up visits 2, 4, 8, 12, and 16 weeks after the baseline visit. These may include repeats of some of the baseline tests.


Condition Intervention Phase
HIV, Inflammation
Drug: Assess Safety
Drug: Effect of drug on viral load
Drug: Effect of drug on T-cell count
Drug: Effect of drug on inflammatory biomarkers
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Participant, Care Provider, Investigator
Primary Purpose: Treatment
Official Title: A Phase 1 Study of CC-11050 in Human Immunodeficiency Virus-1-Infected Adults With Suppressed Plasma Viremia on Antiretroviral Therapy

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Frequency and severity of AEs and SAEs in subjects receiving study agent vs placebo [ Time Frame: 12/30/2016 ]

Secondary Outcome Measures:
  • Plasma HIV-1 RNA levels by both conventional and single-copy assay at Weeks 0,2,4,8, and 12 [ Time Frame: week 12 ]
  • CD4+ T cell counts and percentages at weeks 2,4,8 and 12 [ Time Frame: week 12 ]
  • Markers of systemic inflammation (TNF, IL-6, CRP, IFNy, sCD14, D-dimer) at weeks 2,4,8 and 12 [ Time Frame: week 12 ]

Enrollment: 36
Study Start Date: December 24, 2015
Study Completion Date: May 15, 2017
Primary Completion Date: May 15, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
CC-11050 200mg (2 capsules) BID with food
Drug: Assess Safety
Assess the safety of a 12-week course if CC-1150 in HIV-infected adults who have been on ART for greater than or equal to 1 year and have suppressed plasma viremia
Drug: Effect of drug on viral load
Evaluate the effect of CC-11050 on plasma HIV-1 RNA levels by both conventional and single copy assay at week 12 and over all evaluable time points
Drug: Effect of drug on T-cell count
Evaluate the effect of CC-11050 on CD4+ T cell counts and percentages at week 12 and over all evaluable time points
Drug: Effect of drug on inflammatory biomarkers
Evaluate the effect of CC-11050 on markers of markers of systemic inflammation (TNF, IL-^, CRP, IFNg, sCD14, D-dimer) at week 12 and over all evaluable time points.
Placebo Comparator: B
Placebo (2 capsules) BID with food
Drug: Assess Safety
Assess the safety of a 12-week course if CC-1150 in HIV-infected adults who have been on ART for greater than or equal to 1 year and have suppressed plasma viremia

Detailed Description:

CC-11050 is a novel anti-inflammatory compound with potential to treat a variety of chronic inflammatory conditions and cytokine storms associated with infectious diseases. CC-11050 is a selective phosphodiesterase-4 inhibitor (PDE4) that is active in several in vivo models of inflammatory disease, inhibiting systemic TNF- production, colitis symptoms of the colon, psoriasiform features in the skin, arthritogenic swelling in the joints, neutrophilia and eosinophilia in the lung, and reducing choroidal neovascularization. These data suggest that CC-11050 may have therapeutic potential for chronic inflammatory conditions and/or as an antiangiogenic treatment. The safety profile of CC-11050 has been investigated in healthy males and in subjects with cutaneous lupus erythematosus; the most frequently reported adverse events were fatigue, headache, upper respiratory infection and pruritus; there were no deaths or serious adverse events.

Inflammation is an important contributor to HIV pathogenesis both prior to and after ART initiation. Inflammatory responses can occur abruptly upon ART initiation (known as immune reconstitution inflammatory syndrome or IRIS) and can be chronic in persons with suppressed plasma HIV viremia who are treated with ART, and has been linked to an excess risk of non-AIDS serious events such as cardiovascular, liver and kidney disease and accelerated bone loss. Corticosteroids to reduce levels of inflammatory cytokines in plasma are a standard therapeutic intervention for IRIS, however a more targeted anti-inflammatory and less broadly immunosuppressive intervention is desirable.

We propose a double-blind, randomized trial to assess the safety of CC-11050 in adults with HIV infection who have taken ART for at least 1 year and have suppressed plasma viremia. Enrolled subjects will be randomized 2:1 to 200 mg CC-11050 or placebo twice daily for 12 weeks. Participants will be evaluated at weeks 0, 2, 4, 8, 12 and 16. Changes in in plasma HIV-1 RNA levels (by clinical assay), CD4+ T cell counts and percentages, and the effect on markers of systemic inflammation (e.g., TNF, IL-6, CRP, IFNg, sCD14, D-dimer) will be measured. The effect of CC-11050 on cellular immune activation (T cells and monocytes), and on viral reservoirs (cell associated HIV DNA and RNA) will also be assessed.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. Adults (greater than or equal to 18 years)
    2. Body mass index (BMI) less than or equal to 35 kg/m2
    3. On ART for a minimum of 1 year and on a stable regimen (according to DHHS guidelines) for at least 3 months prior to screening
    4. Plasma HIV-1 RNA level <50 copies/mL at screening (patients with 50-499 <500 copies/mL at screening may be asked to return for rescreening in four (4) weeks or later
    5. Men and women must be willing to take appropriate precautions to prevent pregnancy as described below
    6. Willingness to undergo genetic testing
    7. Willingness to allow storage of specimens for future analysis
    8. Negative serum or urine pregnancy test (for women of childbearing potential)
    9. Under the care of a primary care physician outside of the NIH

Contraception: The effects of CC-11050 on the developing human fetus are unknown. For this reason, subjects must agree to not become pregnant. Females of childbearing potential must have a pregnancy test before initiating the study agent and at each study visit. Because of the risk involved, male and female study participants who engage in sexual activities that can result in pregnancy must agree to use of a male or female condom at every potentially reproductive sexual encounter, AS WELL AS one of the other methods listed below, beginning at the baseline visit and continuing until 3 months after discontinuation of the study agent. Acceptable methods are as follows:

  • Hormonal contraception [e.g. consistent use of oral contraceptive pill daily or other hormonal method such as contraceptive implant or injection] (must be started 1 month prior to receiving the first dose of study agent)
  • Diaphragm or cervical cap
  • Intrauterine device (IUD)
  • Male partner with a vasectomy

During the study, if a participant becomes pregnant or suspects they are pregnant, they should inform the study staff and their primary care physician immediately. The study medication will be stopped immediately and if on CC-11050 they will be referred to a high risk pregnancy specialist and followed by the study team for the remainder of the pregnancy or the rest of the study, whichever occurs later.

EXCLUSION CRITERIA:

  1. Body mass index (BMI) less than or equal to 18.5 kg/m2
  2. Protease inhibitor-based ART regimen
  3. ART regimen which includes Cobicistat
  4. Absence of alternate available ART options in case of virologic failure
  5. Serum ALT or AST value Grade >2 or total bilirubin greater than the ULN unless it is indirect due to Gilbert s disease
  6. History of chronic hepatitis B (+HbsAg or +HBV DNA in plasma) and/or C - treated chronic hepatitis C with SVR > 2 years will be accepted.
  7. Cirrhosis of the liver, or any known active or chronic liver disease
  8. Recent history (<30 days) of infection requiring inpatient hospitalization or systemic therapy
  9. Depression. Patients who report depression or, are suspected or known to have depression and are on stable anti-depressants will undergo Psychiatry evaluation and clinical assessments to determine eligibility. These assesments will be done by a psychiatrist and may include: Beck Depression Inventory (BDI), Spielberger State-Trait Anxiety Inventory (STAI), Montreal Cognitive Assessment(MoCA). The BDI, STAI, and MoCA will be administered to patients being considered for study enrollment. The BDI and STAI may be repeated at least once during follow-up visits in those deemed eligible to participate.
  10. Current breastfeeding
  11. Current or anticipated treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (other than antiretrovirals approved for use in the treatment of HIV)
  12. Any experimental medications within 4 weeks prior to screening or anticipated use of such medications during the trial.
  13. Current (4 weeks prior to the first dose of study drug,) or anticipated use of antimetabolites; alkylating agents; or drugs other than ART, herbal preparations (including St. John s wort), and foods (including grapefruit) known to affect activity of the CYP3A4 enzyme pathway
  14. Use of thalidomide, lenalidomide, pomalidomide, systemic corticosteroids within 4 weeks of screening
  15. Any prior history of PDE4 inhibitor use
  16. History of pancreatitis, elevated lipase (less than or equal to 1.5 above the upper limit of normal) or triglyceride level >500 mg/dL.
  17. History of clinically significant metabolic, endocrine, hepatic, renal, hematologic, pulmonary, gastrointestinal, autoimmune or cardiovascular disorders
  18. Uncontrolled hypertension (persistent measurements over 140/90)
  19. Bradycardia, defined as a sinus rhythm <50 beats/min (bpm)
  20. History or presence of a clinically significant abnormal ECG
  21. History of malignancy except cured basal or squamous cell carcinoma of the skin or cutaneous Kaposi s sarcoma not requiring systemic therapy during the trial
  22. Receipt of radiation or cytotoxic chemotherapeutic agents, unless fully recovered from disease by the time of the first dose of study drug as determined by the opinion of the Investigator, or anticipated use of such agents during the study period
  23. Any condition or significant problems that, based on the judgment of the investigator, would increase risk to the subject or would interfere with the subject s ability to comply with protocol requirements.

Co-enrollment Guidelines: Co-enrollment in other trials is restricted, other than enrollment on observational studies or those evaluating the use of a licensed medication. Study staff should be notified of co-enrollment as it may require the approval of the study investigators.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02652546

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Irini Sereti, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02652546     History of Changes
Other Study ID Numbers: 160044
16-I-0044
Study First Received: January 9, 2016
Last Updated: May 16, 2017

Keywords provided by National Institutes of Health Clinical Center (CC):
HIV/AIDS
Immune Activation
Anti-Inflammatory
TNF
Phosphodieterase Inhibitor

Additional relevant MeSH terms:
Inflammation
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Viremia
Pathologic Processes
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Sepsis
Systemic Inflammatory Response Syndrome

ClinicalTrials.gov processed this record on May 25, 2017