Flag of the European Union

EU Clinical Trials Register

Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:

interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC

clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
Clinical Trials Information System (CTIS).

The EU Clinical Trials Register currently displays 43871 clinical trials with a EudraCT protocol, of which 7290 are clinical trials conducted with subjects less than 18 years old. The register also displays information on 18700 older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).

Examples: Cancer AND drug name. Pneumonia AND sponsor name.
How to search [pdf]

Advanced Search:

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

< Back to search results

Clinical Trial Results:
Phase 2a, Randomized, Open-Label Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ISIS 702843 Administered Subcutaneously to Patients with Non-Transfusion Dependent β-Thalassemia Intermedia

Summary
EudraCT number	2019-003505-96
Trial protocol	GR
Global end of trial date	28 Mar 2023

Results information
Results version number	v1(current)
This version publication date	12 Apr 2024
First version publication date	12 Apr 2024
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

ISIS 702843-CS2

ISRCTN number

-

US NCT number

NCT04059406

WHO universal trial number (UTN)

-

Sponsor organisation name

Ionis Pharmaceuticals, Inc.

Sponsor organisation address

2855 Gazelle Court, Carlsbad, CA, United States, 92010

Public contact

Ionis Pharmaceuticals, Inc., Ionis Pharmaceuticals, Inc., +1 (760) 931-9200, globalregulatoryaffairs@ionisph.com

Scientific contact

Ionis Pharmaceuticals, Inc., Ionis Pharmaceuticals, Inc., +1 (760) 931-9200, globalregulatoryaffairs@ionisph.com

Is trial part of an agreed paediatric investigation plan (PIP)

No

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Analysis stage

Final

Date of interim/final analysis

28 Mar 2023

Is this the analysis of the primary completion data?

No

Global end of trial reached?

Yes

Global end of trial date

28 Mar 2023

Was the trial ended prematurely?

Yes

Main objective of the trial

The purpose of this study was to evaluate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of sapablursen administered subcutaneously to participants with non-transfusion dependent β-Thalassemia Intermedia.

Protection of trial subjects

All study subjects were required to read and sign an Informed Consent Form (ICF).

Background therapy

-

Evidence for comparator

-

Actual start date of recruitment

24 Sep 2020

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

No

Number of subjects enrolled per country

Country: Number of subjects enrolled

Türkiye: 7

Country: Number of subjects enrolled

Australia: 3

Country: Number of subjects enrolled

Lebanon: 4

Country: Number of subjects enrolled

Greece: 4

Country: Number of subjects enrolled

Thailand: 11

Worldwide total number of subjects

29

EEA total number of subjects

4

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

0

Adolescents (12-17 years)

0

Adults (18-64 years)

29

From 65 to 84 years

0

85 years and over

0

Subject disposition

Top of page

Recruitment details

71 subjects were screened and 29 subjects were randomized in the study at 15 investigative sites in Australia, Greece, Lebanon, Thailand, and Turkey from 24 September 2020 to 28 March 2023.

Screening details

Subjects with a diagnosis of β-Thalassemia were enrolled in either cohorts A, B, or C to receive sapablursen.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Cohort A: Sapablursen

Arm description

Subjects initially received 30 mg/0.3 mL of sapablursen by SC injection once every four weeks (Q4W) up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg.

Arm type

Experimental

Investigational medicinal product name

Sapablursen

Investigational medicinal product code

Other name

ISIS 702843, IONIS TMPRSS6-LRx

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

30 mg/0.3 millilitre (mL) for at least 1 dose, then 120 mg/1.2 mL by SC route.

Cohort B: Sapablursen

Arm description

Subjects initially received 50 mg/0.5 mL of sapablursen by SC injection once every four weeks (Q4W) up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg.

Arm type

Experimental

Investigational medicinal product name

Sapablursen

Investigational medicinal product code

Other name

ISIS 702843, IONIS TMPRSS6-LRx

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

120 mg/1.2 mL by SC route.

Cohort C: Sapablursen

Arm description

Subjects initially received 80 mg/0.8 mL of sapablursen by SC injection once every four weeks (Q4W) up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg.

Arm type

Experimental

Investigational medicinal product name

Sapablursen

Investigational medicinal product code

Other name

ISIS 702843, IONIS TMPRSS6-LRx

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

120 mg/1.2 mL for 3 consecutive doses, then 160 mg/1.6 mL if dose escalation was allowed based on a demonstration of adequate safety by SC route.

Number of subjects in period 1	Cohort A: Sapablursen	Cohort B: Sapablursen	Cohort C: Sapablursen
Started	6	6	17
Completed	1	1	2
Not completed	5	5	15
Voluntary Withdrawal	-	2	4
Investigator Judgement	-	-	1
Adverse Event or Serious Adverse Event (SAE)	-	1	-
Study Terminated by Sponsor	5	2	10

Baseline characteristics

Top of page

Reporting group title

Cohort A: Sapablursen

Reporting group description

Subjects initially received 30 mg/0.3 mL of sapablursen by SC injection once every four weeks (Q4W) up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg.

Reporting group title

Cohort B: Sapablursen

Reporting group description

Subjects initially received 50 mg/0.5 mL of sapablursen by SC injection once every four weeks (Q4W) up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg.

Reporting group title

Cohort C: Sapablursen

Reporting group description

Subjects initially received 80 mg/0.8 mL of sapablursen by SC injection once every four weeks (Q4W) up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg.

Reporting group values	Cohort A: Sapablursen	Cohort B: Sapablursen	Cohort C: Sapablursen	Total
Number of subjects	6	6	17
Age Categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	35.0 ± 12.12	31.7 ± 10.44	32.0 ± 10.88	-
Gender categorical
Units: Subjects
Male	2	2	7	11
Female	4	4	10	18
Race
Units: Subjects
White	3	5	9	17
Asian	3	1	8	12
Ethnicity
Units: Subjects
Not Hispanic or Latino	6	6	17	29

End points

Top of page

Reporting group title

Cohort A: Sapablursen

Reporting group description

Subjects initially received 30 mg/0.3 mL of sapablursen by SC injection once every four weeks (Q4W) up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg.

Reporting group title

Cohort B: Sapablursen

Reporting group description

Subjects initially received 50 mg/0.5 mL of sapablursen by SC injection once every four weeks (Q4W) up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg.

Reporting group title

Cohort C: Sapablursen

Reporting group description

Subjects initially received 80 mg/0.8 mL of sapablursen by SC injection once every four weeks (Q4W) up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg.

Primary: Percentage of Subjects with a ≥ 1.0 Grams per Deciliter (g/dL) Increase from Baseline in Hemoglobin (Hb) at Week 27

Top of page

End point title

Percentage of Subjects with a ≥ 1.0 Grams per Deciliter (g/dL) Increase from Baseline in Hemoglobin (Hb) at Week 27 ^[1]

End point description

Full analysis set (FAS) included all randomised subjects who received at least 1 dose of ISIS 702843 and who had at least 1 Hb assessment collected after Day 1. Subjects analysed is the number of subjects available for analysis.

End point type

Primary

End point timeframe

Baseline and Week 27

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: Full analysis set (FAS) included all randomized subjects who received at least 1 dose of sapablursen and who had at least 1 Hb assessment collected after Day 1. Subjects analyzed is the number of subjects available for analysis.

End point values	Cohort A: Sapablursen	Cohort B: Sapablursen	Cohort C: Sapablursen
Number of subjects analysed	6	6	15
Units: Percentage of Subjects
number (confidence interval 95%)
Percentage of Participants	0 (0.0 to 45.9)	0 (0.0 to 45.9)	6.7 (0.2 to 31.9)

No statistical analyses for this end point

Secondary: Percentage of Subjects with a ≥ 1.0 Milligram of Iron per Gram of Dry Weight of Liver (mg Fe/g) Decrease from Baseline in Liver Iron Concentration (LIC) at Week 53

Top of page

End point title

Percentage of Subjects with a ≥ 1.0 Milligram of Iron per Gram of Dry Weight of Liver (mg Fe/g) Decrease from Baseline in Liver Iron Concentration (LIC) at Week 53

End point description

FAS included all randomised subjects who received at least 1 dose of ISIS 702843 and who had at least 1 Hb assessment collected after Day 1. Subjects analysed is the number of subjects available for analysis.

End point type

Secondary

End point timeframe

Baseline and Week 53

End point values	Cohort A: Sapablursen	Cohort B: Sapablursen	Cohort C: Sapablursen
Number of subjects analysed	6	6	14
Units: Percentage of Subjects
number (confidence interval 95%)
Percentage of Participants	33.3 (4.3 to 77.7)	50.0 (11.8 to 88.2)	28.6 (8.4 to 58.1)

No statistical analyses for this end point

Secondary: Percentage of Subjects with a ≥ 1.5 g/dL Increase from Baseline in Hemoglobin (Hb) at Week 53

Top of page

End point title

Percentage of Subjects with a ≥ 1.5 g/dL Increase from Baseline in Hemoglobin (Hb) at Week 53

End point description

FAS included all randomised subjects who received at least 1 dose of ISIS 702843 and who had at least 1 Hb assessment collected after Day 1. Subjects analysed is the number of subjects available for analysis.

End point type

Secondary

End point timeframe

Baseline and Week 53

End point values	Cohort A: Sapablursen	Cohort B: Sapablursen	Cohort C: Sapablursen
Number of subjects analysed	6	6	14
Units: Percentage of Subjects
number (confidence interval 95%)
Percentage of Participants	0 (0.0 to 45.9)	0 (0.0 to 45.9)	0 (0.0 to 23.2)

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

From signing of informed consent to early termination (up to 733 days).

Adverse event reporting additional description

Safety set included all randomized subjects who received at least 1 dose of sapablursen.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.0

Reporting group title

Cohort A: Sapablursen

Reporting group description

Subjects initially received 30 mg/0.3 mL of sapablursen by SC injection once every four weeks (Q4W) up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg.

Reporting group title

Cohort C: Sapablursen

Reporting group description

Subjects initially received 80 mg/0.8 mL of sapablursen by SC injection once every four weeks (Q4W) up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg.

Reporting group title

Cohort B: Sapablursen

Reporting group description

Subjects initially received 50 mg/0.5 mL of sapablursen by SC injection once every four weeks (Q4W) up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg.

Serious adverse events	Cohort A: Sapablursen	Cohort C: Sapablursen	Cohort B: Sapablursen
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 6 (16.67%)	1 / 17 (5.88%)	2 / 6 (33.33%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Injury, poisoning and procedural complications
Forearm Fracture
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Portal vein thrombosis
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
COVID-19
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Cohort A: Sapablursen	Cohort C: Sapablursen	Cohort B: Sapablursen
Total subjects affected by non serious adverse events
subjects affected / exposed	6 / 6 (100.00%)	14 / 17 (82.35%)	6 / 6 (100.00%)
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Injection Site Erythema
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Injection Site Pain
subjects affected / exposed	1 / 6 (16.67%)	0 / 17 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0
Injection Site Pruritus
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Malaise
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	3	0
Non-Cardiac Chest Pain
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	1	0
Peripheral Swelling
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Injection Site Rash
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	2 / 6 (33.33%)
occurrences all number	0	0	2
Vaccination Site Pain
subjects affected / exposed	2 / 6 (33.33%)	1 / 17 (5.88%)	1 / 6 (16.67%)
occurrences all number	3	3	1
Pyrexia
subjects affected / exposed	1 / 6 (16.67%)	5 / 17 (29.41%)	0 / 6 (0.00%)
occurrences all number	3	9	0
Fatigue
subjects affected / exposed	4 / 6 (66.67%)	1 / 17 (5.88%)	1 / 6 (16.67%)
occurrences all number	5	2	1
Reproductive system and breast disorders
Amenorrhoea
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	1	0
Adnexa Uteri Mass
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Ovulation Pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Heavy Menstrual Bleeding
subjects affected / exposed	1 / 6 (16.67%)	0 / 17 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0
Dysmenorrhoea
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	1	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 6 (16.67%)	2 / 17 (11.76%)	0 / 6 (0.00%)
occurrences all number	1	2	0
Oropharyngeal Pain
subjects affected / exposed	1 / 6 (16.67%)	1 / 17 (5.88%)	1 / 6 (16.67%)
occurrences all number	4	1	1
Epistaxis
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	2	0
Nasal Congestion
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	2	0
Pulmonary Hypertension
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Rhinorrhoea
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	1	0
Psychiatric disorders
Panic Attack
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Investigations
Blood Urine Present
subjects affected / exposed	1 / 6 (16.67%)	0 / 17 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0
Injury, poisoning and procedural complications
Vaccination Complication
subjects affected / exposed	1 / 6 (16.67%)	2 / 17 (11.76%)	1 / 6 (16.67%)
occurrences all number	2	4	1
Forearm Fracture
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Congenital, familial and genetic disorders
Odontogenic Cyst
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Nervous system disorders
Headache
subjects affected / exposed	0 / 6 (0.00%)	2 / 17 (11.76%)	2 / 6 (33.33%)
occurrences all number	0	2	2
Sciatica
subjects affected / exposed	1 / 6 (16.67%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	1	1	0
Dizziness
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Tension Headache
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	1	0
Tunnel Vision
subjects affected / exposed	1 / 6 (16.67%)	0 / 17 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0
Blood and lymphatic system disorders
Haemolysis
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	1	0
Thrombocytosis
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	1	0
Ear and labyrinth disorders
Ear Discomfort
subjects affected / exposed	1 / 6 (16.67%)	0 / 17 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0
Eye disorders
Lacrimal Disorder
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	1	0
Gastrointestinal disorders
Abdominal Pain Upper
subjects affected / exposed	1 / 6 (16.67%)	0 / 17 (0.00%)	2 / 6 (33.33%)
occurrences all number	1	0	3
Abdominal Distension
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	2 / 6 (33.33%)
occurrences all number	0	0	2
Abdominal Pain
subjects affected / exposed	1 / 6 (16.67%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	1	3	0
Diarrhoea
subjects affected / exposed	1 / 6 (16.67%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	1	3	0
Nausea
subjects affected / exposed	0 / 6 (0.00%)	2 / 17 (11.76%)	0 / 6 (0.00%)
occurrences all number	0	2	0
Dental Caries
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Dyspepsia
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	1	0
Flatulence
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	1	0
Gastrointestinal Pain
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	1	0
Haemorrhoids
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Periodontal Disease
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	1	0
Vomiting
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	1	0
Toothache
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	1	0
Umbilical Hernia
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Hepatobiliary disorders
Jaundice
subjects affected / exposed	1 / 6 (16.67%)	0 / 17 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0
Hepatomegaly
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Hepatic Mass
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	1	0
Skin and subcutaneous tissue disorders
Dermatitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Dry skin
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Eczema
subjects affected / exposed	1 / 6 (16.67%)	0 / 17 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0
Skin Ulcer
subjects affected / exposed	1 / 6 (16.67%)	0 / 17 (0.00%)	0 / 6 (0.00%)
occurrences all number	3	0	0
Urticaria
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	1	0
Renal and urinary disorders
Renal Disorder
subjects affected / exposed	1 / 6 (16.67%)	0 / 17 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0
Microalbuminuria
subjects affected / exposed	1 / 6 (16.67%)	0 / 17 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0
Hypertonic Bladder
subjects affected / exposed	1 / 6 (16.67%)	0 / 17 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0
Haematuria
subjects affected / exposed	1 / 6 (16.67%)	0 / 17 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0
Proteinuria
subjects affected / exposed	1 / 6 (16.67%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	1	1	0
Dysuria
subjects affected / exposed	1 / 6 (16.67%)	0 / 17 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0
Endocrine disorders
Thyroid Mass
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Musculoskeletal and connective tissue disorders
Myalgia
subjects affected / exposed	2 / 6 (33.33%)	3 / 17 (17.65%)	1 / 6 (16.67%)
occurrences all number	2	4	1
Back Pain
subjects affected / exposed	1 / 6 (16.67%)	2 / 17 (11.76%)	2 / 6 (33.33%)
occurrences all number	1	2	3
Arthralgia
subjects affected / exposed	1 / 6 (16.67%)	0 / 17 (0.00%)	0 / 6 (0.00%)
occurrences all number	2	0	0
Bone Pain
subjects affected / exposed	1 / 6 (16.67%)	0 / 17 (0.00%)	0 / 6 (0.00%)
occurrences all number	2	0	0
Flank Pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	2
Neck Pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Osteopenia
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	1	0
Pain in Jaw
subjects affected / exposed	1 / 6 (16.67%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	1	0	0
Pain in Extremity
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	1 / 6 (16.67%)
occurrences all number	0	1	1
Infections and infestations
Hordeolum
subjects affected / exposed	1 / 6 (16.67%)	0 / 17 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0
Bacterial Vaginosis
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Tonsillitis
subjects affected / exposed	1 / 6 (16.67%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	1	1	0
Gastroenteritis
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	1 / 6 (16.67%)
occurrences all number	0	1	1
Impetigo
subjects affected / exposed	1 / 6 (16.67%)	0 / 17 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0
Influenza
subjects affected / exposed	2 / 6 (33.33%)	1 / 17 (5.88%)	2 / 6 (33.33%)
occurrences all number	2	1	3
Upper Respiratory Tract Infection
subjects affected / exposed	2 / 6 (33.33%)	4 / 17 (23.53%)	0 / 6 (0.00%)
occurrences all number	3	8	0
COVID-19
subjects affected / exposed	6 / 6 (100.00%)	11 / 17 (64.71%)	4 / 6 (66.67%)
occurrences all number	3	5	0
Urinary Tract Infection
subjects affected / exposed	1 / 6 (16.67%)	2 / 17 (11.76%)	0 / 6 (0.00%)
occurrences all number	1	3	0
Pneumonia
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1
Onychomycosis
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	1	0
Nasopharyngitis
subjects affected / exposed	0 / 6 (0.00%)	1 / 17 (5.88%)	0 / 6 (0.00%)
occurrences all number	0	1	0
Infected Skin Ulcer
subjects affected / exposed	1 / 6 (16.67%)	0 / 17 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0
Staphylococcal Infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 17 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

08 Sep 2020

The following changes were made as part of Amendment 1: 1. Added sections related to the coronavirus disease 2019 (COVID-19) pandemic. 2. For Inclusion Criterion 4, changed the definition of non-transfusion dependent from no more than 6 to no more than 8 transfusions in the past 12-month period. 3. Changed Inclusion Criterion 7 from “Chelators was permitted provided the patient has been on a stable dose for at least 3 months prior to Day 1…” to “Chelators was permitted provided the dose has not been increased for at least 2 months prior to Day 1…” 4. Added Exclusion Criterion 9b for proteinuria manifesting as urine protein-to-creatinine ratio (UPCR) ≥ 0.50 milligrams per milligram (mg/mg). 5. Added the platelet count safety panel. 6. Changed the stopping rule related to proteinuria from permanently stopping sapablursen treatment based on a confirmed UPCR result ≥ 0.50 mg/mg to a dose pause based on a confirmed UPCR result that was either: (i) ≥ 0.50 mg/mg that also represented an increase from baseline of at least 2 x, or (ii) ≥ 0.70 mg/mg. 7. Added the allowed concomitant therapy of treatment with either luspatercept-aamt (Reblozyl®) or erythropoietin (EPO), not both, after Day 365 (Week 53).

17 May 2021

The following changes were made as part of Amendment 2: 1. Increased the sapablursen dose levels from 30 mg in Cohort A, 50 mg in Cohort B, and 80 mg in Cohort C to those identified in Section 9.1 and the maximum dose per 28-day interval from 120 to 160 mg based on the safety profiles and nonclinical toxicity results at that time. 2. Decreased the number of evaluable subjects planned from approximately 36 to approximately 24 subjects overall, reduced the thresholds for the number of subjects needed for the Interim Analysis (IA)s , and decreased maximum enrollment from 45 to 30 subjects. 3. For Inclusion Criterion 5, widened the upper limit of the mean Hb acceptable range from 10.0 to 10.5 g/dL and revised the temporary stopping rules for Hb results to correspond with this increase of 0.5 g/dL. 4. For Exclusion Criterion 6, decreased the lower limit for platelet count Screening results from lower limit of normal to 120,000/ cubic millimeters (mm^3).

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
28 Mar 2023	The study was terminated by the Sponsor's decision.	-

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

The study was terminated as per Sponsor’s decision due to a lack of efficacy.

For support, Contact us.

The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

European Medicines Agency © 1995-Fri May 03 12:58:26 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands