Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS TMPRSS6-LRx

Sponsor

Ionis Pharmaceuticals, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04059406

Collaborator

(none)

Enrollment

Locations

Arm

36.2

Anticipated Duration (Months)

1.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose is to evaluate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of IONIS TMPRSS6-LRx administered subcutaneously to participants with non-transfusion dependent β-Thalassemia Intermedia.

Condition or Disease	Intervention/Treatment	Phase
Beta Thalassemia Intermedia	Drug: IONIS TMPRSS6-LRx	Phase 2

Detailed Description

This is a multi-center, randomized, open-label study in up to 45 participants. The duration of each participant in the study will be approximately 29 months and will include an approximately 2-month screening period, a 24-month treatment period, and a 3-month post-treatment period.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

36 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A 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

Actual Study Start Date :

Sep 24, 2020

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IONIS TMPRSS6-LRx A single injection of IONIS TMPRSS6-LRx at multiple dose levels, administered subcutaneously every 4 weeks	Drug: IONIS TMPRSS6-LRx IONIS TMPRSS6-LRx administered subcutaneously

Arm

Intervention/Treatment

Experimental: IONIS TMPRSS6-LRx

A single injection of IONIS TMPRSS6-LRx at multiple dose levels, administered subcutaneously every 4 weeks

Drug: IONIS TMPRSS6-LRx

IONIS TMPRSS6-LRx administered subcutaneously

Outcome Measures

Primary Outcome Measures

Percentage of participants with a ≥ 1.0 grams per deciliter (g/dL) increase from Baseline in hemoglobin (Hb) at Week 27 [Baseline and Week 27]

Secondary Outcome Measures

Percentage of participants with a ≥ 1.5 grams per deciliter (g/dL) increase from Baseline in hemoglobin (Hb) at Week 53 [Baseline and Week 53]
Percentage of participants 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 [Baseline and Week 53]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Willingness to comply with study procedures
Clinical diagnosis of Beta-Thalassemia Intermedia with genotypic confirmation
Non-transfusion dependent, as defined by: no more than 6 transfusions in the past 12-month period, and no transfusions in the 8-week period prior to Day 1
Mean Hb within the range of 6.0-10.0 g/dL, inclusive at Screening
LIC within the range of 3.0-20.0 mg Fe/g dry weight, inclusive
If using chelators, must be on a stable dose for at least 3 months with LIC > 5.0 mg Fe/g dry weight and serum ferritin > 300 nanograms per milliliter (ng/mL)
Females must be non-pregnant and non-lactating, and either surgically sterile or postmenopausal
Males must be surgically sterile, abstinent or using an acceptable contraceptive method

Exclusion Criteria:

Clinically significant abnormalities in lab values, medical history, or physical examination
α-globin gene triplication
Symptomatic splenomegaly
Platelet count < lower limit of normal (LLN) or > 1,000 x 10^9/L
Significant concurrent/recent coagulopathy, history of non-traumatic significant bleeding; history of immune thrombocytopenic purpura (ITP); current use of SC anti-coagulants; history of thrombotic events, including stroke or DVT
Clinically significant renal, liver or cardiac dysfunction
Uncontrolled hypertension (> 140 mm Hg systolic or > 90 mm Hg diastolic)
Fasting blood glucose > 2.0 × upper limit of normal (ULN)
Inability to have a magnetic resonance imaging (MRI) scan
Known history or positive test for human immunodeficiency virus (HIV), hepatitis C (HCV), or hepatitis B (HBV)
Active infection requiring systemic antiviral or antimicrobial therapy
Regular excessive use of alcohol
Recent start of hydroxyurea (6 months prior to Day 1)
Treatment with or recent exposure to another investigational drug, biological agent, ASO, small interfering ribonucleic acid (siRNA), or device within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer; or treatment with or exposure to:
sotatercept (ACE-011), luspatercept (ACE-536), or ruxolitinib within 4 months of Screening
hematopoietic stimulating agents or any hypoxia-inducible factor prolyl hydroxylase inhibitors within 8 weeks of Day 1
prior bone marrow transplant, stem cell transplant, or gene therapy
Surgery associated with significant blood loss within 4 months of Screening, splenectomy within 12 months of Screening, or splenectomy scheduled during treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Royal Prince Alfred Hospital	Camperdown	New South Wales	Australia	2050
2	Monash Medical Centre	Clayton	Victoria	Australia	3168
3	Royal Perth Hospital	Perth	Western Australia	Australia	6000
4	Aghia Sophia General Children's Hospital	Athens	Attica	Greece	115 27
5	University General Hospital of Patras	Patra	Peloponnese	Greece	26 504
6	Koutlimbaneio & Triantafylleio General Hospital of Larissa	Larissa	Thessaly	Greece	412 21
7	Ippokrateio (Hippokration) General Hospital of Athens	Athens		Greece	115 27
8	Chronic Care Center	Hazmiyeh		Lebanon
9	Siriraj Hospital	Bangkok		Thailand	10700
10	Maharaj Nakorn Chiang Mai Hospital	Chiang Mai		Thailand	50200
11	Srinagarind Hospital	Khon Kaen		Thailand	40002
12	Thammasat University Hospital	Pathum Thani		Thailand	12120
13	King Chulalongkorn Memorial Hospital	Pathum Wan		Thailand	10330
14	Naresuan University Hospital	Phitsanulok		Thailand	65000
15	Songklanagarind Hospital	Songkhla		Thailand	90110
16	Cukurova Üniversitesi Tıp Fakültesi	Adana		Turkey	1330
17	Hacettepe Üniversitesi Tıp Fakültesi	Ankara		Turkey	6100
18	Akdeniz University Faculty of Medicine	Antalya		Turkey	07070
19	Medical Park Antalya Hastanesi	Antalya		Turkey	07160
20	Ege Universitesi Tip Fakultesi	İzmir		Turkey	35100
21	İstanbul Üniversitesi - Istanbul Tıp Fakültesi	Topkapı		Turkey	34093

Sponsors and Collaborators

Ionis Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Ionis Pharmaceuticals, Inc.

ClinicalTrials.gov Identifier:

NCT04059406

Other Study ID Numbers:

ISIS 702843-CS2
2019-003505-96

First Posted:

Aug 16, 2019

Last Update Posted:

Jan 5, 2022

Last Verified:

Jan 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Keywords provided by Ionis Pharmaceuticals, Inc.

Thalassaemia

Beta Thalassemia

IONIS TMPRSS6-LRx

Additional relevant MeSH terms:

Thalassemia

beta-Thalassemia

Study Results

No Results Posted as of Jan 5, 2022