Clinical trial NCT02483078 (phase 2/phase 3, status: completed)
Conditions: hiv
ICD codes: B20, Z71.7, O98.72, Z21, O98.73, R75, Z11.4
Drugs: pro 140, placebo, optimized background regimen
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(C)=O)[C@@H](C)O)[C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=CC=C1)C(N)=O
Eligibility criteria:

        Inclusion Criteria:

          1. Males and females, age ≥ 18 years

          2. Exclusive CCR5-tropic virus at Screening Visit

          3. Have a history of at least 3 months on current antiretroviral regimen

          4. Treatment-experienced HIV-infected patients with documented genotypic or phenotypic
             resistance to at least one ART drug within three drug classes

             OR

             Treatment-experienced HIV-infected patients with documented genotypic or phenotypic
             resistance to at least one ART drug within two drug classes and have limited treatment
             options. The options may be limited as a result of drug antiretroviral class
             cross-resistance or documented treatment intolerance.

          5. Be willing to remain on treatment without any changes or additions to the OBT regimen,
             except for toxicity management or upon meeting criteria for treatment failure.

          6. Plasma HIV-1 RNA ≥ 400 copies/mL at Screening Visit and documented detectable viral
             load (HIV-1 RNA >50 copies/ml) within the last 3 months prior to Screening Visit.

          7. Laboratory values at Screening of:

               -  Absolute neutrophil count (ANC) ≥ 750/mm3

               -  Hemoglobin (Hb) ≥ 10.5 gm/dL (male) or ≥ 9.5 gm/dL (female)

               -  Platelets ≥ 75,000 /mm3

               -  Serum alanine transaminase (SGPT/ALT) < 5 x upper limit of normal (ULN)

               -  Serum aspartate transaminase (SGOT/AST) < 5 x ULN

               -  Bilirubin (total) < 2.5 x ULN unless Gilbert's disease is present or subject is
                  receiving atazanavir in the absence of other evidence of significant liver
                  disease

               -  Creatinine ≤ 1.5 x ULN

          8. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered
             not clinically significant by the Principal Investigator

          9. Both male and female patients and their partners of childbearing potential must agree
             to use 2 medically accepted methods of contraception (e.g., barrier contraceptives
             [male condom, female condom, or diaphragm with a spermicidal gel], hormonal
             contraceptives [implants, injectables, combination oral contraceptives, transdermal
             patches, or contraceptive rings], and intrauterine devices) during the course of the
             study (excluding women who are not of childbearing potential and men who have been
             sterilized). Females of childbearing potential must have a negative serum pregnancy
             test at Screening visit and negative urine pregnancy test prior to receiving the first
             dose of study drug.

         10. Willing and able to participate in all aspects of the study, including use of SC
             medication, completion of subjective evaluations, attendance at scheduled clinic
             visits, and compliance with all protocol requirements as evidenced by providing
             written informed consent.

        Note: Subjects diagnosed with either substance dependence or substance abuse or any history
        of a concomitant condition (e.g., medical, psychologic, or psychiatric) may be enrolled if
        in the opinion of site investigator these circumstances would not interfere with the
        subject's successful completion of the study requirements.

        Exclusion Criteria:

          1. Documented CXCR4-tropic virus or Dual/Mixed tropic (R5X4) virus

          2. Patients with no viable treatment options (≤ 1 fully active drug)

          3. Any active infection or malignancy requiring acute therapy (with the exception of
             local cutaneous Kaposi's sarcoma) Note: Subjects infected by the hepatitis B virus or
             early stage hepatitis C virus will be eligible for the study.

          4. Laboratory test values of ≥ grade 3 DAIDS laboratory abnormality with the exception of
             the absolute CD4+ count criterion of < 200/mm3

          5. Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant
             during the study

          6. Unexplained fever or clinically significant illness within 1 week prior to the first
             study dose

          7. Any vaccination within 2 weeks prior to the first study dose.

          8. Subjects weighing < 35kg

          9. History of anaphylaxis

         10. History of Bleeding Disorder or patients on anti-coagulant therapy

         11. Participation in an experimental drug trial(s) within 30 days of the Screening Visit
             or during the study

         12. Any known allergy or antibodies to the study drug or excipients

         13. Treatment with any of the following:

               -  Radiation or cytotoxic chemotherapy with 30 days prior to the Screening Visit or
                  during the study

               -  Immunosuppressants within 60 days prior to the Screening Visit or during the
                  study

               -  Immunomodulating agents (e.g., interleukins, interferons), hydroxyurea, or
                  foscarnet within 60 days prior to the Screening Visit or during the study

               -  Oral or parenteral corticosteroids within 30 days prior to the Screening Visit or
                  during the study. Subjects on chronic steroid therapy > 5 mg/day will be excluded
                  with the following exception:

                    -  Subjects on inhaled, nasal, or topical steroids will not be excluded.

         14. Any other clinical condition that, in the Investigator's judgment, would potentially
             compromise study compliance or the ability to evaluate safety/efficacy