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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05499013




Registration number
NCT05499013
Ethics application status
Date submitted
29/07/2022
Date registered
12/08/2022
Date last updated
22/04/2024

Titles & IDs
Public title
Study to Assess SLN124 in Patients With Polycythemia Vera
Scientific title
Phase 1/2 Study With an Open-label Dose Escalation Phase Followed by a Randomized, Double-blind Phase of SLN124 in Patients With Polycythemia Vera
Secondary ID [1] 0 0
SANRECO
Secondary ID [2] 0 0
SLN124-004
Universal Trial Number (UTN)
Trial acronym
SLN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Polycythemia Vera 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SLN124
Treatment: Drugs - Placebo

Experimental: Phase 1 open-label SLN124 - SLN124 for subcutaneous (s.c.) injection

Experimental: Phase 2 Blinded SLN124 - SLN124 for subcutaneous (s.c.) injection

Placebo Comparator: Phase 2 Blinded Placebo - Sodium chloride for s.c. injection


Treatment: Drugs: SLN124
SLN124 is a double-stranded small interfering ribonucleic acid (siRNA) targeting transmembrane protease, serine 6 (TMPRSS6) messenger ribonucleic acid (mRNA).

Treatment: Drugs: Placebo
sodium chloride, solution for injection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of treatment-emergent adverse events (AEs)
Timepoint [1] 0 0
Day 239
Primary outcome [2] 0 0
Assessment of the number of phlebotomies at intervals
Timepoint [2] 0 0
6 months prior to dosing to Day 239
Secondary outcome [1] 0 0
Pharmacokinetic: area under the plasma concentration (AUC)
Timepoint [1] 0 0
Day 127
Secondary outcome [2] 0 0
Pharmacokinetic: peak plasma concentration (Cmax)
Timepoint [2] 0 0
Day 127
Secondary outcome [3] 0 0
Pharmacodynamic: change in haematocrit
Timepoint [3] 0 0
Day 1 to Day 239
Secondary outcome [4] 0 0
Pharmacodynamic: Change in Transferrin saturation (TSAT)
Timepoint [4] 0 0
Day 1 to Day 239
Secondary outcome [5] 0 0
Pharmacodynamic: Change in Hepcidin
Timepoint [5] 0 0
Day 1 to Day 239

Eligibility
Key inclusion criteria
- Male and female patients aged 18 years or older.

- A confirmed diagnosis of PV according to the revised 2016 World Health Organization
criteria:

- Suitable phlebotomy history

- Must agree to adhere to appropriate contraception requirements

- Patients who are not receiving cytoreductive therapy must have been discontinued from
any prior cytoreductive therapy for at least 24 weeks before dosing and have recovered
from any adverse events due to cytoreductive therapy.

- Patients receiving cytoreductive therapy with hydroxyurea, interferon, busulfan or
ruxolitinib must have received a stable dose of cytoreductive therapy for at least 12
weeks before dosing and with no planned change in dose.

- Patients must have had a dermatological examination within 6 months prior to
screening.

- Must have an Eastern Cooperative Oncology Group score of 0, 1, or 2.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Drug intolerance:

1. History of intolerance to oligonucleotides, or GalNAc, or any component of
SLN124.

2. History of intolerance to s.c. injections.

- Clinically significant thrombosis (e.g., deep vein thrombosis or splenic vein
thrombosis) within 12 weeks of screening.

- History of major bleeding events and/or a requirement for blood transfusion therapy
owing to bleeding in the last 6 months prior to screening.

- Meets the criteria for post-PV myelofibrosis as defined by the International Working
Group-Myeloproliferative Neoplasms Research and Treatment

- Any investigational drug less than 6 weeks prior to the first dose of study drug or
not recovered from effects of prior administration of any investigational agent.

- Any investigational or marketed product using GalNAc targeting less than 48 weeks
prior to administration of any investigational agent.

- Clinically significant co-morbidities

- Biochemical and hematological parameters:

1. Biochemical evidence of significant liver disease during screening

2. Hematological parameters at screening as follows: platelets 1,000,000/µL; or
white blood cell (WBC) count > 25,000/µL; or peripheral blasts < 1%.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/01/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2025
Actual
Sample size
Target
65
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Pindara Private Hospital - Benowa
Recruitment hospital [2] 0 0
Ashford Cancer Centre Research - Kurralta Park
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 0 0
Alfred Health - Melbourne
Recruitment hospital [5] 0 0
Epworth HealthCare - Richmond
Recruitment hospital [6] 0 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 0 0
4217 - Benowa
Recruitment postcode(s) [2] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
3121 - Richmond
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Michigan
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Bulgaria
State/province [5] 0 0
Kyustendil
Country [6] 0 0
Bulgaria
State/province [6] 0 0
Plovdiv
Country [7] 0 0
Malaysia
State/province [7] 0 0
Johor
Country [8] 0 0
Malaysia
State/province [8] 0 0
Pahang
Country [9] 0 0
Malaysia
State/province [9] 0 0
Sarawak
Country [10] 0 0
Malaysia
State/province [10] 0 0
Selangor
Country [11] 0 0
Malaysia
State/province [11] 0 0
Terengganu
Country [12] 0 0
Poland
State/province [12] 0 0
Gdansk
Country [13] 0 0
Poland
State/province [13] 0 0
Katowice
Country [14] 0 0
Poland
State/province [14] 0 0
Lublin
Country [15] 0 0
Poland
State/province [15] 0 0
Skorzewo
Country [16] 0 0
Poland
State/province [16] 0 0
Walbrzych

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Silence Therapeutics plc
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1/2, multicenter study with an open-label dose escalation followed by a
randomized placebo controlled and double-blind phase of SLN124 in adult patients with
Polycythemia Vera (PV) to assess the safety, tolerability, efficacy, pharmacokinetic (PK),
and Pharmacodynamic (PD) response of SLN124.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05499013
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Silence Therapeutics Patient Information
Address 0 0
Country 0 0
Phone 0 0
+44 (0) 20 3457 6900
Fax 0 0
Email 0 0
patient-info@silence-therapeutics.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05499013