A Phase 2 Trial to Evaluate the Efficacy of PRM-151 in Subjects with Idiopathic Pulmonary Fibrosis (IPF)
- CTRC Outpatient
- Clements University Hospital
- UT Southwestern Ambulatory Services
Rhoda Annoh Gordon
Corey Kershaw, M.D.
Study design and Methods:
Subjects who are determined to be eligible, will be enrolled in the study and randomly allocated to treatment with PRM-151 or placebo. Subjects will receive study drug treatment for 24 weeks.
approximately 117 subjects will be randomly assigned on a 2:1 basis (PRM-151: Placebo) as follows:
PRM-151 10 mg/kg iV infusion over 60 minutes on days 1, 3, and 5, then one infusion every 4 weeks
Placebo iV infusion over 60 minutes on Week days 1, 3, and 5, then one infusion every 4 weeks.
Randomization will also be stratified according to pirfenidone or nintedanib versus no iPF treatment .
after completion of study treatment through Week 24, all subjects may receive PRM-151 10 mg/kg iV infusion over 60 minutes Days 1, 3, and 5, then once every 4 weeks for up to an additional 96 weeks in an open label study extension.
Dosing will be administered on Days 1, 3, and 5 will be repeated once every 28weeks during the extension.
oucome variables and study enpoints:
efficacy will be evaluated through pulmonary function tests (PFTs), high resolution CT (HRCT), 6-minute walk test (6MWT), and Patient Reported outcomes (PRos).
The comparison of PRM-151 with placebo will be carried out via a 2-sided statistical test with a type-one error rate of 0.10.
The two treatment arms will be compared using analysis of variance (anoVa), with change from baseline to Week 28 in FVC% predicted as dependent variable (outcome), and treatment and stratum, as explanatory variables.
The primary endpoint is the mean change in FVC % predicted from Baseline to Week 28.
* unless otherwise stated all endpoints will be analysed based on mean change from baseline to Week 28 for the following:
-Total lung volume and volume of parenchymal features on HRCT representative of interstitial lung abnormalities (iLa).
- Volume of parenchymal features on HRCT representative of normal lung.
-Correlation between mean change in FVC % predicted and mean change in total lung volume and volume of parenchymal features on HRCT representative of iLa.*
- incidence of aes, Saes, Proportion of subjects discontinuing study drug due to aes, Change from Baseline in hematology and serum chemistries.
all-cause mortality and Mortality due to respiratory deterioration.
Disease related events associated with mortality:
-unscheduled healthcare professional visits, urgent care visits, and hospitalizations due to respiratory status deterioration.
- acute onset of symptoms, new radiographic abnormalities, The absence of an identified infectious etiology by routine clinical practice
- exclusion of alternative causes by routine clinical practice
Pulmonary Function Tests
- Proportion (%) of subjects with a decline in FVC% predicted of [GreaterThanorequalTo] 5% and [GreaterThanorequalTo] 10%, a decline in FVC in ml of [GreaterThanorequalTo] 100 ml and [GreaterThanorequalTo] 200 ml, an increase in FVC % predicted of [GreaterThanorequalTo] 5% and [GreaterThanorequalTo] 10%, an increase in FVC in ml of [GreaterThanorequalTo]100 ml and [GreaterThanorequalTo] 200 ml, with stable disease by FVC %, defined as a change in FVC % predicted of [Less Than]5%, with stable disease by FVC in ml, defined as a change in FVC of [Less Than] 100ml from Baseline to Week 28.
- Mean change in % predicted Hb-corrected diffusion capacity of carbon monoxide (DLCo).
- Change in 6-minute walk distance.
- examine the change from Baseline at Weeks 4, 8, 12, 16, 20, 24 and 28 for the FVC (% and ml) predicted, 6MWT distance
- Transitions between all categories of lung features.
- Correlation of transitions between categories of lung features by quantitative imaging and changes in FVC% predicted and between categories of lung features by quantitative imaging and changes in Hb-corrected DLCo.
- impact of inspiratory effort on results of HRCT quantitative imaging.
Patient Reported outcomes ( PRos):
- Serum and cellular biomarkers and response according to baseline genetic characteristics
1. Subject is aged 40-80 years.
2. Subject has IPF satisfying the ATS/ERS/JRS/ALAT diagnostic criteria
In the absence of a surgical lung biopsy, HRCT must be
* consistent with UIP
* defined as meeting either criteria A, B, and C, or criteria A and C, or criteria B and C below:
A. Definite honeycomb lung destruction with basal and peripheral predominance.
B. Presence of reticular abnormality AND traction bronchiectasis consistent with fibrosis, with basal and peripheral predominance.
C. Atypical features are absent, specifically nodules and consolidation. Ground glass opacity, if present, is less extensive than reticular opacity pattern.
If on pirfenidone or nintedanib, subject must have been on a stable dose of pirfenidone or nintedanib for at least 3 months prior to screening without increase in FVC% predicted on two consecutive PFTs, including screening PFTs. Subjects may not be on both pirfenidone and nintedanib.
4. If not currently receiving pirfenidone or nintedanib, subject must have been off pirfenidone or nintedanib for >= 4 weeks before baseline.
5. Subject has a FVC >= 50% and <= 90% of predicted.
6. Subject has an Hb corrected and/or Hb uncorrected DLCO >= 25% and <= 90% of predicted.
7. Minimum distance on 6MWT of 150 meters with or without supplemental oxygen.
8. Subject has a forced expiratory volume in 1 second (FEV1)/FVC ratio > 0.70.
9. Women of child bearing potential (WCBP), defined as a sexually mature woman not surgically sterilized or not post-menopausal for at least 24 consecutive months if <= 55 years or 12 months if > 55 years, must have a negative serum pregnancy test within four weeks prior to the first dose of study drug and must agree to use highly effective methods of birth control throughout the study. Highly effective methods of contraception include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation by oral, intravaginal, or transdermal administration; progestogen-only hormonal contraception associated with inhibition of ovulation by oral, injectable, or implantable administration; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; partner vasectomy, and total abstinence (only if total abstinence is the preferred method and usual lifestyle of the subject). Adequate contraceptive use should be continued until 28 days after the final dose of the study drug.
10. Subject has a life expectancy of at least 9 months
11. Subject, according to the investigator[Single Quote]s best judgment, can comply with the requirements of the protocol.
12. Subject and the treating physician considered all medicinal treatment options and / or possibly a lung transplantation prior to considering participation in the study. If the subject is on a lung transplant list, the investigator anticipates the subject will be able to complete the study prior to transplant.
13. Subject has provided written informed consent to participate in the study.