A Phase 2b/3, Multicenter Study to Assess the Treatment Strategy of Using PRO 140 SC as Long-Acting Single-Agent Maintenance Therapy for 48 Weeks in Virologically Suppressed Subjects With CCR5-tropic HIV-1 Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 562
- 试验地点
- 12
- 主要终点
- Proportion of Participants Who Remain on PRO 140 Monotherapy Regimen at the End of Week 48 Without Experiencing Virologic Failure
研究概览
简要总结
This study is a Phase 2b/3, multi-center study designed to evaluate the efficacy, safety, and tolerability of the strategy of shifting clinically stable patients receiving suppressive combination antiretroviral therapy to PRO 140 monotherapy and maintaining viral suppression for 48 weeks following study entry.
Consenting patients will be shifted from combination antiretroviral regimen to weekly PRO 140 monotherapy for 48 weeks during the Treatment Phase with the one week overlap of existing retroviral regimen and PRO 140 at the beginning of the study treatment and also one week overlap at the end of the treatment in subjects who do not experience virologic failure.
详细描述
The primary objective is to assess the treatment strategy of using PRO 140 SC as long-acting, single-agent maintenance therapy for the chronic suppression of CCR5-tropic HIV-1 infection. In addition, the prognostic factors of therapeutic success of PRO 140 monotherapy will be evaluated.
The secondary objective of the trial is to assess the clinical efficacy, safety and tolerability parameters following substitution of combination antiretroviral therapy with weekly PRO 140 monotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females, age ≥18 years
- •Receiving combination antiretroviral therapy for last 24 weeks
- •No change in ART within last 4 weeks prior to Screening Visit
- •Subject has two or more potential alternative approved ART drug options to consider.
- •Exclusive CCR5-tropic virus at Screening Visit
- •Plasma HIV-1 RNA < 50 copies/mL at Screening Visit
- •CD4 cell count of > 200 cells/mm3 since initiation of anti-retroviral therapy
- •CD4 cell count of > 350 cells/mm3 in preceding 24 weeks and at Screening Visit
- •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
- •Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator.
- •Both male and female patients and their partners of childbearing potential must agree to use 2 medically accepted methods of contraception during the course of the study.
- •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.
排除标准
- •CXCR4-tropic virus or dual/mixed tropic (R5X4) virus determined by the Trofile™ DNA Assay
- •Hepatitis B infection as manifest by the presence of Hepatitis B surface antigen (HBsAg)
- •Any active infection or malignancy requiring acute therapy (with the exception of local cutaneous Kaposi's sarcoma)
- •Laboratory test values ≥ grade 4 DAIDS laboratory abnormality.
- •Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the study
- •Unexplained fever or clinically significant illness within 1 week prior to the first study dose
- •Any vaccination within 2 weeks prior to the first study dose or during the study.
- •Subjects who have failed on a maraviroc containing regimen.
- •Subjects weighing < 35kg
- •History of anaphylaxis to any oral or parenteral drugs
- •History of Bleeding Disorder or patients on anti-coagulant therapy
- •Participation in an experimental drug trial(s) within 30 days of the Screening Visit
- •Any known allergy or antibodies to the study drug or excipients
- •Treatment with any of the following:
- •Radiation or cytotoxic chemotherapy with 30 days prior to the screening visit
- •Immunosuppressants within 60 days prior to the screening visit
- •Immunomodulating agents (e.g., interleukins, interferons), hydroxyurea, or foscarnet within 60 days prior to the screening visit
- •Oral or parenteral corticosteroids within 30 days prior to the Screening Visit. 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
- •Any other clinical condition that, in the Investigator's judgment, would potentially compromise study compliance or the ability to evaluate safety/efficacy
研究组 & 干预措施
Part 1 - 525 mg weekly injections of PRO 140, no VF (Group B)
525 mg SC injections of PRO 140 per week, patients who had no Virologic Failure (VF)
干预措施: PRO 140 (525 mg) (Drug)
Part 1 - 700 mg weekly injections of PRO 140 (Group C)
700 mg SC injections of PRO 140 per week
干预措施: PRO 140 (700 mg) (Drug)
Part 1 - 350 mg weekly injections of PRO 140, no VF (Group A)
350 mg SC injections of PRO 140 per week, patients who had no Virologic Failure (VF)
干预措施: PRO 140 (350 mg) (Drug)
Part 2 - Rescue Arm for Group A, 525 mg PRO 140
525 mg SC injections of PRO 140 per week after experiencing virologic failure on 350 mg dose
干预措施: PRO 140 (525 mg) (Drug)
Part 2 - Rescue Arm for Group B, 700 mg PRO 140
700 mg SC injections of PRO 140 per week after experiencing virologic failure on 525 mg dose
干预措施: PRO 140 (700 mg) (Drug)
Part 2 - Rescue Arm for Group A, 700 mg PRO 140
700 mg SC injections of PRO 140 per week after experiencing virologic failure on 350 mg dose
干预措施: PRO 140 (700 mg) (Drug)
结局指标
主要结局
Proportion of Participants Who Remain on PRO 140 Monotherapy Regimen at the End of Week 48 Without Experiencing Virologic Failure
时间窗: From T1 (first treatment administration) to week 48 (T48).
The proportion of participants experiencing virologic failure was analyzed and reported. Virological failure is defined as two consecutive plasma HIV-1 RNA levels of \>= 200 copies/mL.
次要结局
- Proportion of Participants Experiencing Virologic Failure While on PRO 140 Monotherapy Regimen(From T1 (first treatment administration) to week 48 (T48).)
- Time to Virologic Failure After Initiating PRO 140 Monotherapy(From T1 (first treatment administration) to week 48 (T48).)
- Proportion of Participants Achieving Viral Suppression (HIV-1 RNA < 50 Copies/mL) After Experiencing Virologic Failure.(From T1 (first treatment administration) to subsequent visit when viral re-suppression achieved (up to 52 weeks).)
- Time to Achieving Viral Suppression (HIV-1 RNA < 50 Copies/mL) After Experiencing Virologic Failure(From T1 (first treatment administration) to subsequent visit when viral re-suppression achieved (up to 52 weeks).)
- Proportion of Participants With Viral Suppression (HIV-1 RNA < 50 Copies/mL) at Week 48 From the Start of PRO 140 Treatment Phase.(From T1 (first treatment administration) to week 48 (T48).)
- Measurement of Treatment Adherence to the PRO 140 Monotherapy Regimen(From T1 (first treatment administration) to week 25 (T25).)
- Total Time That Participants Remain Off Combination ART Regimen, Defined as the Time Between Start of PRO 140 Monotherapy and Restart of Combination ART Regimen(From T1 (first treatment administration) to last visit, up to 20 months.)
- Mean Change in CD4 Cell Count, at Each Visit Within the Treatment Phase(From T1 (first treatment administration) to week 48 (T48).)
- Proportion of Participants Within Each Treatment Group Experiencing Emerging Resistance(From T1 (first treatment administration) to VF visit (up to 7 months).)
- Mean HIV-1 RNA Concentrations in CSF in Central Nervous System (CNS) Sub-study(From T1 (first treatment administration), T4 (week 4), and VF visit (up to 7 months).)
- Mean PRO 140 Concentration in Plasma for Central Nervous System (CNS) Sub-study(From T1 (first treatment administration), T4 (week 4), and VF visit (up to 7 months).)
- Mean PRO 140 Concentrations in CSF for Central Nervous System (CNS) Sub-study(From T1 (first treatment administration), T4 (week 4), and VF visit (up to 7 months).)
- Mean HIV-1 RNA Concentrations in Genital Secretion in Genitourinary (GU) Sub-study(From T1 (first treatment administration), T4 visit (week 4), and T16 visit (up to 16 weeks).)