Clinical Trial Results:
A novel therapy using recombinant human PTH 1-84 to stimulate bone repair and enhance fracture healing in the acute Charcot foot: a double blind placebo controlled phase IV trial
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Summary
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EudraCT number |
2009-016873-13 |
Trial protocol |
GB |
Global end of trial date |
25 Jul 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Dec 2018
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First version publication date |
20 Dec 2018
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Other versions |
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Summary report(s) |
FINAL STUDY REPORT |
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 |
PTHinCharcotfoot
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
King's College Hospital NHS Foundation Trust
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Sponsor organisation address |
Denmark Hill, London, United Kingdom, SE5 9RS
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Public contact |
Investigator's Trial Team, Kings College Hospital NHS Foundation Trust, 0044 203299 5124, nina.petrova@nhs.net
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Scientific contact |
Investigator's Trial Team, Kings College Hospital NHS Foundation Trust, 0044 203299 5124, nina.petrova@nhs.net
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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 |
30 Oct 2013
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Oct 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
25 Jul 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Can recombinant human parathyroid hormone (rh PTH 1-84) accelerate clinical resolution of the acute Charcot foot by enhancing bone repair and fracture healing. This will be asssessed in terms of:
• Time to resolution of the acute Charcot foot
• Percentage of patients with a clinical outcome of Charcot foot resolution by 6 months
• Percentage of patients with a clinical outcome of Charcot foot resolution by 12 months
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Protection of trial subjects |
We will also undertake a safety evaluation monthly for the first 3 months and then
at three monthly intervals until termination of treatment. This will include
physical examinations, vital signs (sitting systolic and diastolic blood pressure,
heart rate, respiratory rate and body temperature) and assessment of adverse
events (AEs) and serious adverse events (SAEs), and laboratory measurement of
serum calcium, phosphate and creatinine. We will also record adherence to
medications.
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Background therapy |
All patients will receive standard treatment which includes treatment with cast immobilisation and Calcium and Vitamin D supplementation (1000 mg Ca++/ daily and 800IU of Vitamin D3). This will include 2 tablets daily of Calceos. Each tablet Calceos contains Calcium carbonate 1.25g equivalent to 500 mg lemental calcium or Ca2+ 12.5 mmol and 10 micrograms colecalciferol (vitamin D3) equivalent to 400 units). | ||
Evidence for comparator |
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Actual start date of recruitment |
01 Oct 2010
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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 |
United Kingdom: 46
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Worldwide total number of subjects |
46
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EEA total number of subjects |
46
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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) |
46
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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 |
Participants were recruited from one clinical site in London UK between 2010 and 2013. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Inclusion Criteria Aged 18 to 75 years inclusive Has diabetes mellitus either Type 1 or Type 2 Has acute Charcot osteoarthropathy defined as recent onset of a unilateral hot swollen foot with foot skin temperature 2oC greater than the contralateral foot. Patients should either have bone fracture and joint subluxation on standard | ||||||||||||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||
Blinding implementation details |
The placebo has the same composition as the active drug except without the PTH 1-84. The powder in the placebo is composed of mannitol, citric acid monohydrate, sodium chloride 0.4%, dilute hydrochloric acid (for pH adjustment) and sodium hydroxide 1N (for pH) adjustment; the solvent is metacresol and water
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Group A - Active | ||||||||||||||||||
Arm description |
Treatment A: active treatment will be 100µg rhPTH 1-84 (Preotact) administered subcutaneously (s.c.) daily | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Preotact
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and solvent for solution for injection in cartridge
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Patients will receive 100μg of parathyroid hormone administered once-daily as a
subcutaneous injection into the abdomen.
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Arm title
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Group B - Placebo | ||||||||||||||||||
Arm description |
Treatment B: Placebo treatment will be100µg placebo administered subcutaneously (s.c.) daily | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
The investigational product is Preotact. Nycomed UK Ltd is the MAH for Preotact 100 micrograms powder and solvent for solution for injection, which is supplied as the Preotact pen device which is a dual-chamber cartridge. The first chamber contains 1.61 mg parathyroid hormone. Each dose of 71.4 microliter contains 100 micrograms parathyroid hormone.
The placebo has the same composition as the active drug except without the PTH 1- 84. The powder in the placebo is composed of mannitol, citric acid monohydrate, sodium chloride 0.4%, dilute hydrochloric acid (for pH adjustment) and sodium hydroxide 1 N (for pH) adjustment; the solvent is metacresol and water.
Patients will receive 100μg of parathyroid hormone/ placebo administered once-daily as a subcutaneous injection into the abdomen for 12 months.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
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End points reporting groups
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Reporting group title |
Group A - Active
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Reporting group description |
Treatment A: active treatment will be 100µg rhPTH 1-84 (Preotact) administered subcutaneously (s.c.) daily | ||
Reporting group title |
Group B - Placebo
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Reporting group description |
Treatment B: Placebo treatment will be100µg placebo administered subcutaneously (s.c.) daily | ||
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End point title |
Primary Endpoint [1] | |||||||||
End point description |
The primary objective is to determine whether there is a difference between active treatment with rh PTH 1-84 and standard treatment alone in terms of Time to resolution of the Charcot foot in relation to the adverse event of a skin foot temperature difference of greater than 2°C between the Charcot and the contralateral foot Percentage of patients with a clinical outcome of Charcot foot resolution by 6 months. This will be expressed as a binary indicator for resolution of the acute Charcot foot (in relation to the adverse event of a difference of greater than 2°C between the Charcot and the contralateral foot).
Percentage of patients with a clinical outcome of Charcot foot resolution by 12 months. This will be expressed as a binary indicator for resolution of the acute Charcot foot (in relation to the adverse event of a difference of greater than 2°C between the Charcot and the contralateral foot).
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End point type |
Primary
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End point timeframe |
12 months
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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: See attached document for results. |
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Attachments |
Results |
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End point title |
Secondary Endpoint | |||||||||
End point description |
The secondary objectives will be to determine whether there is a difference between active treatment with rh PTH 1-84 and standard treatment alone in terms of: Percentage of patients with healed fractures at clinical resolution on foot and ankle radiographs Percentage of patients with bony union and healing of fractures at the time of clinical resolution on MRI scans Rate of change of bone turnover markers from baseline and up to clinical resolution of the Charcot foot Rate of change of score in quality of life from baseline up to clinical resolution using the SF-36 Rate of change of score in quality of life from baseline and up to clinical resolution using the EQ-5D;
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End point type |
Secondary
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End point timeframe |
12 months
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Adverse events information [1]
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Timeframe for reporting adverse events |
Adverse Events reported throughout the trial and for a period of 30 days after the last treatment visit or early termination visit
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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 |
17.1
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Reporting groups
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Reporting group title |
Active
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
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| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: See document |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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12 Jul 2010 |
Change to IMP label. |
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12 Jul 2011 |
To amend the duration of treatment phase.
To amend the study protocol to clarify that the renal function will be assessed by estimated
glomerular filtration rate (eGFR) AND/OR creatinine clearance
To amend the inclusion and exclusion criteria.
To amend the visit for the measurement of skin foot temperatures.
To amend the protocol to cancel the home visit by the nurse 2 weeks post randomisation.
To update the manufacturer site due to change of address |
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11 Jul 2014 |
To reduce the subject recruitment sample size from 92 to 46. This reduction is due to a slow recruitment process and expiry of available IMP. |
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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 | |||
