Phase I Dose Escalation Trial to Evaluate Safety and Reactogenicity of Single IV Administration of P2G12
试验速览
- 阶段
- 1 期
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Number of participants with treatment-related adverse events and serious adverse events assessed by CTCAE v4.0.
研究概览
简要总结
A randomised phase I trial of a monoclonal antibody which neutralises HIV-1 (P2G12) to be given as a single intravenous infusion to healthy human volunteers to assess the safety and reactogenicity
详细描述
Study disease:
In 2014 it was estimated that 36.9 million people worldwide were living with HIV and since the beginning of the epidemic, about 36 million have died of HIV.
There are many research strategies underway to try to reduce the devastating effects of this disease and to prevent onward transmission, and it is likely that a range of these used simultaneously will be required to bring the epidemic under control. These include the development of a vaccine, microbicide, antiviral treatment and agents used in prevention. Amongst these, a HIV neutralising antibody that is safe when infused intravenously could play an important role either in post exposure, or when HIV is driving an aggressive disease and there is a need to lower the viral load abruptly or when mothers present in labour with high viral loads.
The clinical advancement of monoclonal antibodies has been hampered by the inability to manufacture the specific recombinant proteins with a system that would be scalable for the global market. There is also a valid perception that even if manufacturing was possible, it would be at a totally unaffordable cost. Thus, neutralising monoclonal antibodies such as MAbs b12 have only reached efficacy studies in rhesus macaques. In the case of monoclonal antibodies it is generally believed that a cocktail of at least 3 antibodies would be necessary to avoid viral escape, thereby potentially tripling the cost of a product, as compared with a conventional single monoclonal antibody therapeutic. It is clear that in order to progress these promising anti-HIV monoclonal antibodies, new methods of manufacture need to be developed.
Investigational Medicinal Product (IMP):
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Volunteers aged between 18 and 45 years on the day of screening
- •Available for follow-up for the duration of the study
- •Willing and able to give written informed consent
- •At low risk of HIV and willing to remain so for the duration of the study defined as:
- •no history of injecting drug use in the previous ten years
- •no gonorrhoea or syphilis in the last six months
- •no high risk partner (e.g. injecting drug use, HIV positive partner) either currently or within the past six months
- •no unprotected anal intercourse in the last six months, outside a relationship with a regular partner known/presumed to be HIV negative
- •no unprotected vaginal intercourse in the last six months outside a relationship with a regular known/presumed HIV negative partner
- •Willing to undergo a HIV test
- •If sexually active, using an effective method of contraception with partner (combined oral contraceptive pill; injectable or implanted contraceptive; any IUCD/IUS; consistent record with condoms if using these; physiological or anatomical sterility in self or partner) from 14 days prior to the first infusion until 4 months after, and willing to undergo urine pregnancy tests as per schedule
- •Agree to abstain from donating blood for three months after the end of their participation in the trial, or longer if necessary
- •Registered with a GP
- •Satisfactory response received from GP before randomisation
排除标准
- •Pregnant or lactating
- •Clinically relevant abnormality on history or examination including
- •history of grand-mal epilepsy
- •skin disorder might prevent insertion of IV line
- •liver disease with inadequate hepatic function (grade 1 or greater as described in appendix 3)
- •haematological, metabolic, gastrointestinal or cardio-pulmonary disorders
- •uncontrolled infection; immunodeficiency or use of immunosuppressives in preceding 3 months (including systemic steroids for longer than 14 days)
- •history of renal disease
- •history of autoimmune disease
- •Known hypersensitivity to any component of the infusion used in this trial, or have severe or multiple allergies to drugs or pharmaceutical agents
- •History of severe local or general reaction to vaccination which according to the investigators judgement might prevent participation
- •Receipt of blood products or immunoglobulin within 4 months of screening
- •Participation in another trial of a medicinal product, completed less than 30 days prior to enrolment
- •HIV 1/2 positive or indeterminate on screening
- •Positive for hepatitis B surface antigen, hepatitis C antibody or serology indicating active syphilis requiring treatment
- •A clinically significant amount of protein or blood in the urine
- •Grade 1 or above routine laboratory parameters (see appendix 3 for definitions). Hyperbilirubinemia to be considered an exclusion criterion only when confirmed to be conjugated bilirubinaemia
- •Unable to read and speak English to a fluency level adequate for the full comprehension of procedures required in participation and consent.
- •Unlikely to comply with protocol or the PI has any concerns about suitability of participation in the study
研究组 & 干预措施
Dose cohort 1
P2G12 0.125g
干预措施: P2G12 Dose Cohort 1 (Drug)
Dose cohort 2
P2G12 0.25g
干预措施: P2G12 Dose Cohort 2 (Drug)
Dose cohort 3
P2G12 0.5g
干预措施: P2G12 Dose Cohort 3 (Drug)
结局指标
主要结局
Number of participants with treatment-related adverse events and serious adverse events assessed by CTCAE v4.0.
时间窗: three months
Number of participants with local and systemic reactogenicity signs and symptoms post-infusion
时间窗: three months
次要结局
- Serum concentration of P2G12 in participants in the active study cohorts(three months)