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Trial registered on ANZCTR


Registration number
ACTRN12615001144505
Ethics application status
Approved
Date submitted
28/08/2015
Date registered
28/10/2015
Date last updated
29/09/2022
Date data sharing statement initially provided
29/09/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase I/IIa Study of DVC1-0101 in Subjects with Intermittent Claudication or Critical Limb Ischaemia Secondary to Peripheral Artery Disease
Scientific title
A Phase I/IIa Study investigating the safety and tolerability of intramuscular DVC1-0101 compared with placebo in patients with Intermittent Claudication or Critical Limb Ischaemia Secondary to Peripheral Artery Disease.
Secondary ID [1] 287329 0
None
Universal Trial Number (UTN)
U1111-1173-5200
Trial acronym
n/a
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Intermittent claudication secondary to peripheral artery disease 295968 0
Critical limb ischaemia secondary to peripheral artery disease 296376 0
Condition category
Condition code
Cardiovascular 296249 296249 0 0
Diseases of the vasculature and circulation including the lymphatic system
Cardiovascular 296647 296647 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A single dose (30 intramuscular injections) of DVC1-0101 or placebo will be administered to the affected lower leg limb. The doses planned for this study are:
* DVC1-0101, 5 x 10^9 ciu/patient (High dose)
* DVC1-0101, 1 x 10^9 ciu/patient (Low dose)
* Placebo
Participants will be invited to participate in an optional extension period following completion of a six month period (open-label), All participants in the extension period will receive a single dose (30 IM injections) of DVC1-0101, 5 x 10^9 ciu/patient (High dose).

The study drug will be administered in the clinical research unit to the lower limb of the most affected leg. Thirty intramuscular injections will be administered to pre-determined locations between the knee and ankle.
Intervention code [1] 292648 0
Treatment: Drugs
Comparator / control treatment
Placebo: phosphate buffered saline solution (DPBS)
Control group
Placebo

Outcomes
Primary outcome [1] 295905 0
The primary endpoint of this trial, the safety and tolerability (combined end point) of the study drug at high and low dose vs placebo, will be assessed by the frequency, grade, and duration of treatment-emergent adverse events (AEs) including clinically significant changes in safety laboratory parameters, ECGs and vital signs. Additional tolerability assessments will be measured using injection site reaction diaries, which will be maintained for 14 days post dose.
Timepoint [1] 295905 0
Day 1 (6 hours post-dose), Day 2, 7, 14, 30, then 3 months, 6 months and 12 months post-dose
Secondary outcome [1] 316904 0
*To evaluate the efficacy of DVC1-0101 compared with placebo in participants with PAD–IC or PAD-CLI, using absolute claudication distance (ACD) measured by treadmill test as a measure of efficacy.
Timepoint [1] 316904 0
Baseline, Day 30, 3 months and 6 months post-dose
Secondary outcome [2] 316905 0
To evaluate the effect of DVC1-0101 on treadmill claudication onset time (COT) as measured using the exercise treadmill test..
Timepoint [2] 316905 0
Baseline, Day 30, 3 months and 6 months post-dose
Secondary outcome [3] 318002 0
To evaluate the effect of DVC1-0101 on Quality of Life (QOL), as measured using the Walking Impairment Questionnaire (WIQ).
Timepoint [3] 318002 0
Baseline, Day 30, 3 months and 6 months post-dose
Secondary outcome [4] 318003 0
To measure the effects of DVC1-0101 on ankle brachial index (ABI) or toe brachial index (TBI).
Timepoint [4] 318003 0
Baseline, Day 30, 3 months and 6 months post-dose
Secondary outcome [5] 318004 0
To measure the effects of DVC1-0101 on resting pain using a visual analogue scale (VAS).
Timepoint [5] 318004 0
Baseline, Day 30, 3 months and 6 months post-dose
Secondary outcome [6] 318007 0
To measure the pharmacokinetic / pharmacodynamic effects of DVC1-0101 by the collection of blood samples for virus titer, genome copy count and virus antibody titers.
Timepoint [6] 318007 0
Day 1 (6 hours post-dose), Day 2, 7, 14, 30, then 3 months, 6 months and 12 months post-dose
Secondary outcome [7] 318428 0
To evaluate the effect of DVC1-0101 on treadmill claudication onset time (COT) as measured using the exercise treadmill test.
Timepoint [7] 318428 0
Baseline, Day 30, 3 months and 6 months post-dose

Eligibility
Key inclusion criteria
Diagnosis of PAD secondary to atherosclerosis, confirmed by medical history and one of the following observed in either leg at the screening visit:
a. Resting ABI less than or equal to 0.90
b. Resting ABI greater than 0.90 and less than or equal to 1.30, with a reduction of greater than or equal to 0.20 in ABI when measured within 2 minutes after completion of treadmill exercise.
c. TBI less than 0.75 if the subject has non-compressible calf arteries. i.e. Rutherford category 1-5. (Rutherford RJ, 1997)

Claudication symptoms of stable severity for at least 3 months prior to screening OR the highest ACD from either the screening or baseline exercise treadmill test (ETT), utilizing a modified Gardner protocol, must be between 1 and 12 minutes (inclusive).
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
PAD secondary to non-atherosclerotic conditions.

Proximal severe obstructive disease amenable to revascularisation.

Lower extremity amputation(s), including a toe amputation, which interfere(s) with walking on the treadmill.

Percutaneous revascularization procedure within 3 months prior to Screening, or procedures that are planned during the study.

Poorly controlled diabetes mellitus as evidenced by a haemoglobin A1C (HbA1c) > 12%.

Coronary artery bypass graft surgery (CABG), open peripheral vascular revascularization, or major surgical procedures within 3 months prior to screening, or planned at any time during the study

Unstable cardiovascular disease (CVD), defined as unstable both by clinical criteria and / or major changes in medication within 3 months prior to Screening or Baseline of the Extension Period.

History of congestive heart failure (CHF) or presence of CHF as defined by modified Framingham criteria class II- IV.

Myocardial infarction (MI) within 3 months prior to Screening or at Baseline of the Extension Period.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
A randomisation code will be provided to the pharmacist by the sponsor/CRO and will be maintained in the unblinded pharmacy folder in pharmacy. Participants will be randomised in a 1:1:1 ratio to each treatment group. Study drug will be transported to site, and study personnel involved with drug administration will be blinded to the treatment allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer generated randomisation scheme will be generated by a statistician on behalf of the sponsor/CRO.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
An optional extension period will be available to participants who remain eligible for the study at the end of the 6 month follow up period. The procedures for the extension period will be the same as the original treatment period, although all participants will receive high dose DVC1-0101 in an open label fashion.
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
All endpoints, demographics, vital signs, and study compliance measures will be listed by cohort, subject, and study visit. Continuous parameters will be summarised by their frequencies, mean, standard deviation, minimum, maximum, and median values for each cohort. Summaries will include values at each visit and the change from baseline value. Categorical parameters will be summarized using frequencies and proportions per treatment group.

The primary endpoint of this trial, the safety and tolerability of the study drug at high and low dose vs placebo, will be assessed by the frequency, grade, and duration of treatment-emergent adverse events (AEs) including clinically significant changes in safety laboratory parameters.

All treatment emergent AEs will be listed along with their grade, duration and time of onset by treatment group, and subject. Furthermore, the number and percent of each AE code will be summarized by treatment group. Safety laboratory parameters will be listed by treatment group, subject and study visit. Continuous raw and change from baseline safety laboratory parameters will be summarized in tables by their frequency, mean, standard deviation, minimum, maximum and median by treatment group and study visit. Parameters of clinical relevance will also be presented graphically as treatment group means over time. Categorical safety laboratory parameters will be summarized in tables by frequency and proportion within each cohort and study visit.

Efficacy based secondary endpoints include measurements of ABI and TBI, ACD and COT as assessed by a Treadmill Test, quality of life assessments as assessed by the WIQ and VAS for pain intensity. ABIs and TBIs for the target leg identified at the Baseline Visit and PWT will be reported for all timepoints as well as the change from baseline. The WIQ has 3 aggregate scores which will be calculated and the change from baseline will be presented in summary tables. VAS pain intensity scores will be assessed and reported only for those in with ischemic rest pain.

Analysis will be undertaken by the study sponsor/CRO according to a statistical plan, and an independent reviewer will review the results.

Due to the fact that the placebo cohort, in a previous clinical study showed an ACD improvement of 30%, in order to have statistical power of 0.9, a minimum of 15 study participants are needed. This study is a Phase I/IIa proof of concept study preceding a pivotal study, and each cohort has been set at n=6 (the minimum cohort size “plus one”) for a total of 18 study participants.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
1/09/2016
Actual
22/11/2016
Date of last participant enrolment
Anticipated
31/12/2018
Actual
9/08/2017
Date of last data collection
Anticipated
31/12/2019
Actual
20/09/2018
Sample size
Target
18
Accrual to date
Final
3
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 4257 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 4258 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 10200 0
5000 - Adelaide
Recruitment postcode(s) [2] 10201 0
5011 - Woodville

Funding & Sponsors
Funding source category [1] 291890 0
Commercial sector/Industry
Name [1] 291890 0
ID Pharma Co. Ltd
Country [1] 291890 0
Japan
Primary sponsor type
Commercial sector/Industry
Name
CMAX - a division of IDT Australia
Address
Level 5

18a North Terrace
Adelaide
SA 5000
Country
Australia
Secondary sponsor category [1] 290555 0
Government body
Name [1] 290555 0
SAHMRI
Address [1] 290555 0
North Terrace
Adelaide SA 5000
Country [1] 290555 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293399 0
Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [1] 293399 0
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000
Ethics committee country [1] 293399 0
Australia
Date submitted for ethics approval [1] 293399 0
06/07/2015
Approval date [1] 293399 0
21/09/2015
Ethics approval number [1] 293399 0
AU/1/C1EF17

Summary
Brief summary
This study aims to investigate the safety and tolerability of intramuscular DVC1-0101 injections, at both high and low doses, when compared with placebo, in patients with intermittent claudication or critical limb ischaemia secondary to peripheral arterial disease. The secondary aims are to investigate the efficacy of DVC1-0101, compared with placebo, in promoting revascularisation in the target leg limb.

Enrolled participants will receive a single dose (30 intramuscular injections) in the target limb. They will be required to return for regular outpatient visits over a 6 month follow up period. A final follow up phone call will be conducted at 12 months post-dose. Safety and tolerability will be measured via physical examination, clinical laboratory results and monitoring of injection site reactions. Secondary efficacy outcomes include exercise treadmill testing to obtain absolute claudication distance (ACD) and patient self-reported walking impairment data. Blood samples will be collected for pharmacodynamic measurements.

The results of the study will be used to develop DVC1-0101 as a treatment for patients with claudication and critical limb ischaemia.
Trial website
Nil
Trial related presentations / publications
Nil
Public notes

Contacts
Principal investigator
Name 59734 0
Prof Stephen Nicholls
Address 59734 0
SAHMRI
North Terrace
Adelaide SA 5000
Country 59734 0
Australia
Phone 59734 0
+61 8 8128 4510
Fax 59734 0
Email 59734 0
[email protected]
Contact person for public queries
Name 59735 0
Dianne Pepper
Address 59735 0
CMAX
Level 5, 18a North Terrace
Adelaide
SA 5000
Country 59735 0
Australia
Phone 59735 0
+61 8 7088 7900
Fax 59735 0
Email 59735 0
[email protected]
Contact person for scientific queries
Name 59736 0
Stephen Nicholls
Address 59736 0
SAHMRI
North Terrace
Adelaide
SA 5000
Country 59736 0
Australia
Phone 59736 0
[email protected]
Fax 59736 0
Email 59736 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.