Clinical Trial Results:
A Phase 1 Study of DCR-PH1 in Patients with Primary Hyperoxaluria Type 1 (PH1)
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Summary
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EudraCT number |
2015-003142-51 |
Trial protocol |
GB NL |
Global end of trial date |
14 Oct 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Oct 2017
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First version publication date |
20 Oct 2017
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
DCR-PH1-101
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
Orphan drug designation number: EU/3/15/1528, IND: 122598 | ||
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Sponsors
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Sponsor organisation name |
Dicerna Pharmaceuticals, Inc.
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Sponsor organisation address |
87 Cambridgepark Drive, Cambridge, United States, MA 02140
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Public contact |
Ralf Rosskamp, Chief Medical Officer, Dicerna Pharmaceuticals, Inc., 001 6176126270, rrosskamp@dicerna.com
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Scientific contact |
Ralf Rosskamp, Chief Medical Officer, Dicerna Pharmaceuticals, Inc., 001 6176126270, rrosskamp@dicerna.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
14 Oct 2016
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Oct 2016
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To determine the safety and tolerability of DCR-PH1 administered via IV infusion to patients with PH1.
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Protection of trial subjects |
This study was conducted in compliance with the protocol, with Dicerna’s and/or designee’s SOPs and/or guidelines, the US Food and Drug Administration (FDA) regulations, with the ICH GCP guidelines and with the Declaration of Helsinki.
The study design included measures to minimize the possibility of adverse reactions to the investigational product based on previous experiences with oligonucleotide LNP formulations. Appropriate safety monitoring was performed and emergency medical care was available during the conduct and follow-up of the dosing. Patients were instructed to be premedicated with dexamethasone, diphenhydramine, and an H2 blocker (e.g. famotidine, ranitidine) 60 minutes prior to the start of DCR-PH1 infusion. Patients were carefully observed for a minimum of 8 hours following completion of the first administration of study drug (Day 1) for evidence of any TEAEs, and for collection of PK and PD assessments. Patients were monitored throughout the infusion and until 30 minutes after the end of the infusion for Infusion-Related Reactions (IRR). A dose escalation design, with staggered enrollment and treatment of patients within the dose group, was utilized to ensure patient safety.
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Background therapy |
Vitamin B6 doses ranged from 400 mg to 800 mg daily; no subjects changed the dose of vitamin B6 during their participation in the study. | ||
Evidence for comparator |
N/A | ||
Actual start date of recruitment |
13 May 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 1
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Country: Number of subjects enrolled |
Germany: 3
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Worldwide total number of subjects |
4
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EEA total number of subjects |
4
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
4
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was designed to enroll patients with mild to moderate renal insufficiency with a key inclusion criterion the burden of renal desease. First subject first visit was on 13 May 2016. | |||||||||
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Pre-assignment
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Screening details |
Male or female, at least 12 years of age at the time of obtaining informed consent with diagnosis of PH1, confirmed by genotyping for homozygosity or compound heterozygosity in the AGXT (the gene that encodes AGT) gene (historically available genotype information was accepted for study eligibility). | |||||||||
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Period 1
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Period 1 title |
Part A (SAD) portion (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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DCR-PH1, 0.05 mg/kg | |||||||||
Arm description |
Cohort 1: Subjects enrolled in Part A (SAD portion) were to receive a single dose of 0.05 mg/kg DCR-PH1 administered by IV infusion | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
DCR-PH1
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Investigational medicinal product code |
DCR-PH1
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
DCR-PH1 was provided by the sponsor formulated as a sterile, preservative-free liquid for IV injection, in 20-mL single-use glass vials with 40 mg of drug product per vial (2 mg/mL). DCR-PH1 was administered on Day 1, as a continuous IV infusion over approximately 2 hours via a peripheral or central IV catheter following a 1-2-3 rule. During the first 30 minutes, the infusion rate was approximately 1 mL/min, followed by 2 mL/min during the second half of the first hour of infusion. The remaining amount was infused at a rate of no less than 3 mL/min during the second hour of the infusion. The lot number of the drug used was L00205.
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Arm title
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DCR-PH1, 0.1 mg/kg | |||||||||
Arm description |
Cohort 2: Subjects enrolled in Part A (SAD portion) were to receive a single dose of 0.1 mg/kg DCR-PH1 administered by IV infusion | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
DCR-PH1
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Investigational medicinal product code |
DCR-PH1
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
DCR-PH1 was provided by the sponsor formulated as a sterile, preservative-free liquid for IV injection, in 20-mL single-use glass vials with 40 mg of drug product per vial (2 mg/mL). DCR-PH1 was administered on Day 1, as a continuous IV infusion over approximately 2 hours via a peripheral or central IV catheter following a 1-2-3 rule. During the first 30 minutes, the infusion rate was approximately 1 mL/min, followed by 2 mL/min during the second half of the first hour of infusion. The remaining amount was infused at a rate of no less than 3 mL/min during the second hour of the infusion. The lot number of the drug used was L00205.
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Baseline characteristics reporting groups
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Reporting group title |
DCR-PH1, 0.05 mg/kg
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Reporting group description |
Cohort 1: Subjects enrolled in Part A (SAD portion) were to receive a single dose of 0.05 mg/kg DCR-PH1 administered by IV infusion | ||||||||||||||||||||||||||||||||
Reporting group title |
DCR-PH1, 0.1 mg/kg
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Reporting group description |
Cohort 2: Subjects enrolled in Part A (SAD portion) were to receive a single dose of 0.1 mg/kg DCR-PH1 administered by IV infusion | ||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
DCR-PH1, 0.05 mg/kg
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Reporting group description |
Cohort 1: Subjects enrolled in Part A (SAD portion) were to receive a single dose of 0.05 mg/kg DCR-PH1 administered by IV infusion | ||
Reporting group title |
DCR-PH1, 0.1 mg/kg
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Reporting group description |
Cohort 2: Subjects enrolled in Part A (SAD portion) were to receive a single dose of 0.1 mg/kg DCR-PH1 administered by IV infusion | ||
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End point title |
Safety and tolerability as determined by number of subjects with adverse events [1] | |||||||||
End point description |
PK plasma samples collected: Before DCR-PH1 administration on Day 1, approximately at 60 min after the start of infusion, at the end of infusion; at 30, 120, 240, 360 and 480 min after end of infusion; at Days 2, 3, 8 (±1 day), 15 (±1 d), 22 (±1 d), 29 (±1 d).
Blood sample collection for pharmacodynamic analysis (oxalate, glycolate) collected on Day 1, Day 15 (±1 d), Day 22 (±1 d) and end of trial - Day 29 (±1 d).
Urine samples collected: Scr (BL), days 8(±1 day), 15(±1 d), 22 (±1 d)
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End point type |
Primary
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End point timeframe |
Day 1 through EOS or Day 29 (±1 day).
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Due to the early termination of the study and small number of subjects enrolled, no statistical analysis was performed. |
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| No statistical analyses for this end point | ||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Subjects were monitored for AEs from Day 1 through the EOS visit.
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Adverse event reporting additional description |
Safety assessments included recording of all adverse events (AEs), vital sign measurements, physical examinations, laboratory test results. AE's were mild to moderate and no dose limiting toxicities were reported. All safety laboratory results were reported to be within grade 0 to grade 1.
No SAEs were reported during the conduct of the trial.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
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Reporting groups
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Reporting group title |
DCR-PH1, 0.05 mg/kg
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Reporting group description |
Cohort 1: Subjects enrolled in Part A (SAD portion) were to receive a single dose of 0.05 mg/kg DCR-PH1 administered by IV infusion | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
DCR-PH1, 0.1 mg/kg
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Reporting group description |
Cohort 2: Subjects enrolled in Part A (SAD portion) were to receive a single dose of 0.1 mg/kg DCR-PH1 administered by IV infusion | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
