Table 2.
Clinical trials targeting CCL5/RANTES and receptors in human disease.
| Compound name | Strategy | Company/Sponsor | Disease of interest | Official title of clinical studies | Phase and status | Trial number |
|---|---|---|---|---|---|---|
| Cenicriviroc | CCR2 and CCR5 Antagonist | Tobira Therapeutics, Inc. | HIV/AIDS | A Phase IIb randomized, double-blind, double-dummy trial of 100 or 200 mg once-daily doses of cenicriviroc (CVC, TBR 652) or once-daily EFV, each with Open-Label FTC/TDF, in HIV 1-Infected, antiretroviral treatment-Naïve, adult patients with only CCR5-Tropic virus | Phase II: ongoing | NCT01338883 |
| GW873140 | CCR5 Antagonist | GlaxoSmithKline | HIV/AIDS | A Phase III, randomized, double-blind, placebo-controlled, multicenter, parallel group study to compare the efficacy and safety of GW873140 400 mg BID in combination with a ritonavir-containing optimized background therapy regimen versus placebo plus OBT over 48 weeks. | Phase III: terminated | NCT00297076 |
| INCB009471 | CCR5 Antagonist | Incyte Corp. | HIV/AIDS | A randomized, double-blind, placebo-controlled study exploring the safety, tolerability, PK & virological effect of once daily Oral dosing of INCB009471 as monotherapy for 14 days in ARV-naïve/Limited ARV-experienced, HIV-1 infected patients | Phase II: completed | NCT00393120 |
| TBR 652 | CCR5 Antagonist | Tobira Therapeutics, Inc. | HIV/AIDS | A proof of concept, multiple dose-escalating study to evaluate the antiviral activity, safety, and pharmacokinetics of the CCR5 antagonist TBR 652 in HIV 1-infected, antiretroviral treatment-experienced, CCR5 antagonist-naïve patients | Phase I and II: completed | NCT01092104 |
| Maraviroc | CCR5 Antagonist | ViiV Healthcare/Pfizer | HIV/AIDS | Drug use investigation for HIV infection patients of maraviroc (regulatory post marketing commitment plan) | Phase IV: Ongoing | NCT00864474 |
| Maraviroc | CCR5 Antagonist | University of California, San Francisco/National Heart, Lung, and Blood Institute (NHLBI)/Pfizer | HIV/AIDS | Effect of maraviroc on endothelial function in HIV-infected patients | Phase III: Ongoing | NCT00844519 |
| Maraviroc | CCR5 Antagonist | Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal/Pfizer | HIV/AIDS | Pilot study of the effect of a CCR5 coreceptor antagonist on the latency and reservoir of HIV-1 in patients taking highly active antiretroviral therapy | Phase II: ongoing | NCT00795444 |
| Maraviroc | CCR5 Antagonist | ViiV Healthcare/Pfizer | HIV/AIDS | A multicenter, randomized, blinded, placebo-controlled study to evaluate the safety of maraviroc in combination with other antiretroviral agents in HIV-1-infected subjects co-infected with Hepatitis C and/or Hepatitis B virus | Phase IV: ongoing | NCT01327547 |
| Maraviroc | CCR5 Antagonist | University of California, San Francisco/Pfizer/ViiV Healthcare | HIV/AIDS Kaposi Sarcoma | effects of maraviroc on HIV-related kaposi's sarcoma | Phase III: study recruiting | NCT01276236 |
| Maraviroc | CCR5 Antagonist | University of Pennsylvania/Pfizer | GVHD\⊂ Transplantation | Safety and efficacy of maraviroc, a CCR5-inhibitor in prophylaxis of graft-Versus-host disease in patients undergoing non-myeloablative allogeneic stem-cell transplantation | Phase I and II: completed | NCT00948753 |
| Maraviroc | CCR5 Antagonist | National Center for Tumor Diseases, Heidelberg/University Hospital Heidelberg/Pfizer | Colorectal cancer/Liver metastasis | Treatment of advanced colorectal cancer patients with hepatic liver metastases using the CCR5-antagonist maraviroc (phase I maracon trial) | Phase I: recruiting | NCT01736813 |
| Maraviroc | CCR5 Antagonist | Abramson Cancer Center of the University of Pennsylvania/Pfizer | GVHD/Cancer | A phase II study to assess the efficacy of maraviroc, a CCR5-antagonist in prophylaxis of graft-versus-host disease in patients with hematologic malignancies undergoing reduced-intensity allogeneic stem-cell transplantation from unrelated donors | Phase II: recruiting | NCT01785810 |
| Maraviroc | CCR5 Antagonist | S.F.L. van Lelyveld, UMC Utrecht/Pfizer | HIV/Cardiovascular disease | Maraviroc abacavir study - effect on endothelial recovery | Phase IV: recruiting | NCT01389063 |
| GSK706769 | CCR5 Antagonist | GlaxoSmithKline | Rheumatoid arthritis | A randomized, double-blind, placebo-controlled, parallel group study to investigate the ability of GSK706769 to maintain clinical remission after withdrawal of enbrel in patients with rheumatoid arthritis | Phase II: | NCT00979771 |
| Vicriviroc, SCH 417690 | CCR5 Antagonist | Schering-Plough | HIV/AIDS | Vicriviroc in combination treatment with an optimized ART regimen in treatment-experienced subjects with R5/X4 HIV infection (VICTOR-E2; protocol no. P05057) | Phase II: completed | NCT00551330 |
| NI-0701 | Antibody against CCL5 | NovImmune SA | Chemokine blockade | A first in man randomized placebo controlled study of single ascending intravenous doses of NI-0701 in healthy volunteers | Phase I: completed | NCT01255501 |
| PRO 140 | Antibody against CCR5 | Progenics Pharmaceuticals, Inc. | HIV/AIDS | A Phase IIa, randomized, double-blind, placebo controlled study of PRO 140 by subcutaneous administration in adult subjects with Human Immunodeficiency virus Type 1 Infection | Phase II: Completed | NCT00642707 |
| CCR5mAb004 | Antibody against CCR5 | Human Genome Sciences, Inc./GlaxoSmithKline | HIV/AIDS | A Phase I, randomized, placebo-controlled, single-injection, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of Ccr5mab004 (human monoclonal Igg4 antibody to Ccr5) in HIV-1 seropositive individuals who are not receiving concurrent antiretroviral therapy | Phase I: Completed | NCT00114699 |
| HGS1025 | Antibody against CCR5 | Human Genome Sciences, Inc./GlaxoSmithKline | Ulcerative Colitis | A Phase Ib, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Pharmacodynamics and Safety of HGS1025, a Human Monoclonal Anti-CCR5 Antibody, in Subjects With Ulcerative Colitis | Phase I: | NCT01434576 |
| CCX 354-C | CCR1 Antagonist | ChemoCentryx | Rheumatoid arthritis | A Randomized, double-blind, placebo-controlled, phase I/II study to evaluate the safety and efficacy of CCX354-C in subjects with rheumatoid arthritis | Phase I and II: completed | NCT01027728 |
| BAY86-5047, ZK811752, SH T 04268H | CCR1 Antagonist | Bayer | Endometriosis | A Multicenter, double-blind, randomized, placebo-controlled, parallel-group study to evaluate the safety, tolerability and efficacy of the CCR1 antagonist ZK 811752, given orally in a dose of 600 mg three times daily, for the treatment of endometriosis over 12 weeks | Phase II: Completed | NCT00185341 |
| AZD4818 | CCR1 Antagonist | AstraZeneca | COPD | A 4-week double-blind, placebo-controlled, randomized, parallel group phase IIa study to assess the tolerability/safety and efficacy of inhaled AZD4818 in patients with moderate to severe chronic obstructive pulmonary disease | Phase II: Completed | NCT00629239 |
| CP-481,715 | CCR1 Antagonist | Pfizer | Skin allergy | Placebo-controlled, randomized, parallel group, multiple-dose study to evaluate the effects of CP-481,715 on clinical response and cellular infiltration following contact allergen challenge to the skin of nickel allergic subjects. | Phase I: Completed | NCT00141180 |
| GW766944 | CCR3 Antagonist | GlaxoSmithKline | Asthma/Sputum eosinophilia | A Randomized, double-blind, placebo-controlled, parallel group study to compare GW766944 (an oral CCR3 receptor antagonist) versus placebo in patients with asthma and sputum eosinophilia | Phase II: Completed | NCT01160224 |
| SB-728 | Zinc Finger Nuclease modified T cells | University of Pennsylvania/Sangamo Biosciences | HIV/AIDS | A Phase I study of autologous T-cells genetically modified at the CCR5 gene by zinc finger nucleases SB-728 in HIV-infected patients | Phase I: completed | NCT00842634 |
| Lentivirus vector rHIV7-shI-TAR-CCR5RZ | Lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells | City of Hope Medical Center/National Cancer Institute (NCI) | HIV/Cancer | A pilot study of safety and feasibility of stem cell therapy for aids lymphoma using stem cells rreated with a lentivirus vector-encoding multiple anti-HIV RNAs | Phase I: ongoing | NCT00569985 |
| CCR5delta32 hematopoietic stem cell | HLA-compatible hematopoietic stem cell from CCR5delta32homozygotes donors | Medical College of Wisconsin/National Heart, Lung, and Blood Institute (NHLBI)/National Cancer Institute (NCI)/Blood and Marrow Transplant Clinical Trials Network | HIV/Cancer | Allogeneic hematopoietic cell transplant for hematological cancers and myelodysplastic syndromes in HIV-infected individuals | Phase II: recruiting | NCT01410344 |
Description of the clinical trials targeting CCL5/RANTES and its receptors in human disease [139].
AIDS: Acquired immunodeficiency syndrome; COPD: Chronic obstructive pulmonary disease; GVHD: Graft versus host disease; HIV: Human immunodeficiency virus.