A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of FG-3019 in Patients With Idiopathic Pulmonary Fibrosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- FibroGen
- 入组人数
- 160
- 试验地点
- 42
- 主要终点
- Change From Baseline in FVC (Percent of Predicted FVC Value [% Predicted]) to Week 48
研究概览
简要总结
To evaluate the safety and tolerability of pamrevlumab in participants with IPF, and the efficacy of pamrevlumab in slowing the loss of forced vital capacity (FVC) and the progression of IPF in these participants.
详细描述
The study has been amended in February 2016 to further allow for the enrollment of a subgroup of participants (N=60) who will be allowed to receive treatment with approved IPF therapy with pirfenidone or with nintedanib as concomitant therapy.
These additional participants will be stratified by background therapy, randomized to pamrevlumab or placebo, and followed up for 24 weeks. The main objective of the study remains safety. Pharmacokinetic (PK) samples to assess drug concentrations will also be collected.
This sub-study portion only applies to a select United States centers.
Enrollment for the main study was completed on 29 June 2016. Enrollment for the sub-study was completed on 16 December 2016.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants, Investigators, and study staff were blinded to treatment assignments and did not have access to the randomization codes. The high-resolution computed tomography (HRCT) readers were blinded to treatment assignments.
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 40 to 80 years, inclusive.
- •Diagnosis of IPF as defined by current international guidelines. Each participant must have 1 of the following: (1) Usual Interstitial Pneumonia (UIP) Pattern on an available high-resolution computed tomography (HRCT) scan; or (2) Possible UIP Pattern on an available HRCT scan and surgical lung biopsy within 4 years of Screening showing UIP Pattern.
- •History of IPF of ≤5 years duration with onset defined as the date of the first diagnosis of IPF by HRCT or surgical lung biopsy.
- •Interstitial pulmonary fibrosis defined by HRCT scan at Screening, with evidence of ≥10% to <50% parenchymal fibrosis (reticulation) and <25% honeycombing, within the whole lung, as determined by the HRCT central reader.
- •FVC percent of predicted value ≥55% at Screening.
- •Female participants of childbearing potential (including those <1 year postmenopausal) must be willing to use a medically acceptable method of contraception, for example, an oral contraceptive, depot progesterone, or intrauterine device. Male participants with female partners of childbearing potential who are not using birth control as described above must use a barrier method of contraception (for example, condom) if not surgically sterile (for example, vasectomy).
- •For sub-study only: Receiving treatment for IPF with a stable dose of pirfenidone or with a stable dose of nintedanib for at least 3 months before Screening initiation and willing to continue treatment with pirfenidone or with nintedanib according to the corresponding approved label and the prescribing physician, including all listed safety requirements (for example, liver function tests, avoidance of sunlight and sunlamp exposure and wearing of sunscreen and protective clothing daily for pirfenidone, and smoking cessation).
排除标准
- •Women who are pregnant or nursing.
- •Infiltrative lung disease other than IPF, including any of the other types of idiopathic interstitial pneumonias (Travis, 2013); lung diseases related to exposure to fibrogenic agents or other environmental toxins or drugs; other types of occupational lung diseases; granulomatous lung diseases; pulmonary vascular diseases; systemic diseases, including vasculitis and connective tissue diseases.
- •HRCT scan findings at Screening are inconsistent with UIP Pattern, as determined by the HRCT central reader.
- •Pathology diagnosis on surgical lung biopsy is anything other than UIP Pattern, as determined by the local pathologist.
- •The Investigator judges that there has been sustained improvement in the severity of IPF during the 12 months prior to Screening, based on changes in FVC, diffusing capacity of the lung for carbon monoxide (DLCO), and/or HRCT scans of the chest.
- •Clinically important abnormal laboratory tests.
- •Upper or lower respiratory tract infection of any type within 4 weeks of the first Screening visit.
- •Acute exacerbation of IPF within 3 months of the first Screening visit.
- •Use of medications to treat IPF within 5 half-lives of Day 1 dosing. If monoclonal antibodies were used, the last dose of the antibody must be at least 4 weeks before Day 1 dosing. This applies to participants enrolled in Main Study only.
- •Use of any investigational drugs, including any investigational drugs for IPF, within 4 weeks prior to Day 1 dosing.
- •History of cancer diagnosis of any type in the 3 years preceding Screening, excluding non-melanomatous skin cancer, localized bladder cancer, or in situ cancers.
- •Diffusing capacity (DLCO) less than 30% of predicted value.
- •History of allergic or anaphylactic reaction to human, humanized, chimeric, or murine monoclonal antibodies.
- •Previous treatment with FG-
- •Body weight greater than 130 kilograms.
研究组 & 干预措施
Pamrevlumab
Participants will receive pamrevlumab 30 milligram/kilogram (mg/kg) by intravenous (IV) infusion every 3 weeks for a total of 16 infusions over 45 weeks.
干预措施: Pamrevlumab (Drug)
Placebo
Participants will receive placebo matching pamrevlumab by IV infusion every 3 weeks for a total of 16 infusions over 45 weeks.
干预措施: Placebo (Drug)
Sub-Study: Pamrevlumab+Pirfenidone or Nintedanib
Participants will receive pamrevlumab by IV infusion every 3 weeks for a total of 8 infusions over 21 weeks. Initial treatment with pamrevlumab in all active comparator participants will be administered at a dose of 15 mg/kg for the first 2 dose administrations. If these are well tolerated, all following study drug administrations will be at 30 mg/kg.
Pirfenidone or nintedanib will be dosed according to the instructions in their respective labels and the prescribing physician.
干预措施: Pamrevlumab (Drug)
Sub-Study: Placebo+Pirfenidone or Nintedanib
Participants will receive placebo matching pamrevlumab by IV infusion every 3 weeks for a total of 8 infusions over 21 weeks. Initial treatment with placebo in all active comparator participants will be administered at a dose of 15 mg/kg for the first 2 dose administrations. If these are well tolerated, all following study drug administrations will be at 30 mg/kg.
Pirfenidone or nintedanib will be dosed according to the instructions in their respective labels and the prescribing physician.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in FVC (Percent of Predicted FVC Value [% Predicted]) to Week 48
时间窗: Baseline (Screening and Day 1), Week 48
FVC in liters was measured during the spirometry assessments at screening and during the randomized treatment period at Day 1 and every 12 weeks. The FVC (% predicted) was calculated for the corresponding gender-race-age group. The least squares (LS) mean change from Baseline to Week 48 (end of the randomized treatment period) in FVC (% predicted) is presented. Baseline was defined as the mean of the last screening visit and the Day 1 visit values. Other statistical analysis data is reported in the statistical analysis section. Observed data from all visits were included in the model.
次要结局
- Number of Participants With a Respiratory-Related Death(Week 55)
- Mean Change From Baseline in the HRCT Quantitative Lung Fibrosis (QLF) Score to Week 24 and Week 48(Baseline (Screening), Week 24 and Week 48)
- Number of Participants With IPF Progression Events up to Week 48(Baseline (Screening and Day 1) up to Week 48)
- Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48(Baseline (Day 1), Week 24 and Week 48)
- Number of Participants With a Respiratory-Related Hospitalization(Week 55)
- Number of Participants With No Decline in FVC (% Predicted) at Week 48(Baseline (Day 1) to Week 48.)