A phase II feasibility study to assess changes in patients who have been identified as having cognitive function impairment following the addition of a new drug to an existing effective regime of three HIV antiretrovirals drugs

Phase 1

• Conditions: Human Immunodeficiency Virus; MedDRA version: 19.0 Level: PT Classification code 10020161 Term: HIV infection System Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2015-002955-85-GB
• Lead Sponsor: Imperial College London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-12-14
• Study Completion: 2017-01-06
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 7

Inclusion Criteria

1. Aged 18 or over at Screening, male or female subjects
2. Documented HIV-1 infected
3. Undetectable plasma HIV RNA (<200 copies/mL) for at least 6 months
4. Demonstrated clinically significant cognitive impairment (see section 8.3)
5. On cART comprising of BHIVA guideline recommended therapies (2015 guidelines) with the exception of elvitegravir/cobicistat and rilpivirine
6. Comorbidities, if present, are stably managed for at least 6 months
7. No clinically significant recreational drug use or alcohol dependence
8. Male subjects who are heterosexually active must either:
a. Use 2 forms of highly effective barrier contraception (e.g. condom & diaphragm) during heterosexual intercourse from screening through to at least 3 months after discontinuation of study medication
b. Be truly abstinent, when this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception]
9. Female subjects may be eligible to enter and participate into the study if she:
a. Is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and = 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or,
b. Is of child-bearing potential with a negative pregnancy test at both Screening and Day 0 and agrees to use one of the following methods of contraception to avoid pregnancy;
c. Is truly abstinent, when this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception].
d. Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide);
e. Reliable highly effective contraceptives unaffected by enzyme inducers such as copper-bearing intrauterine device (Cu-IUD), Levonorgestrel-containing Intrauterine system (IUS) or progestogen-only injectable with published data showing that the expected failure rate is <1% per year;
f. Male partner sterilization confirmed prior to the female subject’s entry into the study, and this male is the sole partner for that subject;
g. Approved hormonal contraception such as the combined oral, patch or ring contraceptive, and progestogen only pill (POP) or implant must be used with an additional contraceptive precaution, such as condoms, during and for 28 days after stopping Cenicriviroc. This is because Cenicriviroc, a CYP3A4 enzyme inducer, may increase the rate at which these hormonal contraceptives are metabolised;
h. Any other method with published data showing that the expected failure rate is <1% per year
Any contraception method must be used consistently, in accordance with the approved product label and for at least 3 months after discontinuation of study medication.

Are the trial subjects under 18? no
Number

Exclusion Criteria

1. Current major depression (score of 15 or more on PHQ-9 score at study screening)
2. Chronic neurological diseases (e.g. epilepsy and stroke; at the discretion of the investigator)
3. History of severe head injury (with loss of consciousness for >30 minutes)
4. Cerebral AIDS defining infections
5. Current intravenous drug use (past six months)
6. Severe psychiatric disease (at the discretion of the investigator)
7. Contra-indication for MRI scan (e.g. claustrophobia, metal in body, physically unable to lie flat)
8. Contraindications to lumbar-puncture examination (at the discretion of the investigator)
9. Current or previous use of CCR5 inhibitors (maraviroc, cenicriviroc or others)
10. Disallowed medication which may interact with cenicriviroc (section 11.2)
11. Chronic liver disease
12. Breastfeeding
13. Laboratory investigations at screening out with the follow cut-offs:
• Haemoglobin < 8.5 g/dL;
• Absolute neutrophil count < 1000;
• Platelet count < 100,000;
• ALT or AST> 2.5 X upper limit of normal ;
• estimated creatinine clearance < 60 mL/min (Cockcroft and Gault 1979)
14. In the opinion of the investigator unable to comply with study procedures

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified