Back to resultsA Study to Assess the Safety, Tolerability, and Efficacy of IONIS-GHR-LRx Administered in Patients With Acromegaly
Primary Purpose
Acromegaly
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
IONIS-GHR-LRx
Sponsored by
About this trial
This is an interventional treatment trial for Acromegaly focused on measuring acromegaly, IONIS-GHR-LRx
Eligibility Criteria
Inclusion Criteria:
- Males or females with a documented diagnosis of Acromegaly* who are 18 to 75 years old (inclusive) at the time of informed consent.
Have had pituitary surgery (e.g. transsphenoidal) unless there was a contraindication to surgery and are either acromegaly medical treatment naïve, or who had not taken any other acromegaly medications prior to the screening visit as outlined below
- bromocriptine: 2 weeks
- cabergoline: 4 weeks
- quinagolide: 4 weeks
- octreotide daily injection (SC) or oral formulation: 4 weeks
- pegvisomant: 4 weeks
- octreotide LAR: 3 months
- pasireotide LAR: 4 months
- lanreotide (all formulations): 3 months
- At Screening, serum IGF-1 (performed at the central lab) between 1.3 to 5 × ULN, inclusive, adjusted for age and sex.
- Females must be non-pregnant and non-lactating, and either surgically sterile, post-menopausal, abstinent, or using 1 highly effective method of birth control
Exclusion Criteria:
- Participants who received surgery for pituitary adenoma within the last 3 months before the trial, and/or planning to receive surgery during the trial
- Participants who received radiotherapy for pituitary adenoma within the last 2 years before the trial, and/or planning to receive radiotherapy during the trial
- Participants with a pituitary tumor that, per Investigator judgment, is worsening (e.g., either growing or at risk of compressing or abutting the optic chiasm or other vital structures) as assessed by pituitary/sellar MRI protocol at Screening or within 3 months of Screening. CT scan is allowed if MRI is contraindicated
- Evidence of decompensated cardiac function per medical judgement and/or New York Heart Association (NYHA) Class 3 or 4
- Clinical evidence of symptomatic hyperprolactinemia that would necessitate treatment
- Symptomatic cholelithiasis, and/or choledocholithiasis
Sites / Locations
- Cedars-Sinai Medical Center
- Massachusetts General Hospital
- Palm Research Center Inc.
- Memorial Sloan Kettering Cancer Center
- Cleveland Clinic
- Endocrinology Associates, Inc
- Oregon Health & Science University (OHSU)
- East-Tallinn Central Hospital
- Tartu University Hospital
- Debreceni Egyetem Klinikai Kozpont
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
- Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
- Pauls Stradins Clinical University Hospital
- Vaidoto Urbanaviciaus Individuali imone
- Hospital of Lithuanian University of Health Sciences (LSMU) Kauno klinikos
- Zespol Oddzialow Chorob Wewnetrznych, Endokrynologii i Diabetologii
- Uniwersytecki Szpital Kliniczny, im. Jana Mikulicza-Radeckiego we Wroclawiu,
- Centrum Badan Klinicznych Piotr Napora Lekarze Sp. p.
- Centrul Medical Unirea Bucuresti, Endocrinologie
- I.M. Sechenov Moscow First State Medical University
- Clinical Center of Serbia
- Clinical Center of Vojvodina
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
IONIS-GHR-LRx Dose 1
IONIS-GHR-LRx Dose 2
IONIS-GHR-LRx Dose 3
Arm Description
Single dose of IONIS-GHR-LRx Dose 1 will be administered by SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3).
Single dose of IONIS-GHR-LRx Dose 2 will be administered by SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3).
Single dose of IONIS-GHR-LRx Dose 3 will be administered by SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3).
Outcomes
Primary Outcome Measures
Percent Change From Baseline in Insulin-like Growth Factor I (IGF-1) to Week 27
Secondary Outcome Measures
Percentage of Participants who Achieve Normalized IGF-1 Levels to Within 1.2 Times of Gender and Age Limits at Day 183 (Week 27)
Percentage of Participants who Achieve Normalized IGF-1 Levels to Within 1.0 Times of Gender and Age Limits at Day 183 (Week 27)
Change From Baseline in Serum IGF-1 Over Time
Percent Change From Baseline in Serum IGF-1 Over Time
Full Information
NCT ID
NCT04522180
First Posted
August 18, 2020
Last Updated
June 4, 2023
Sponsor
Ionis Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04522180
Brief Title
A Study to Assess the Safety, Tolerability, and Efficacy of IONIS-GHR-LRx Administered in Patients With Acromegaly
Official Title
An Open Label, Randomized, Phase 2 Study to Assess the Safety, Tolerability, and Efficacy of IONIS-GHR-LRx, an Antisense Inhibitor of the Growth Hormone Receptor, Administered Monthly as Monotherapy in Patients With Acromegaly
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
January 4, 2021 (Actual)
Primary Completion Date
July 15, 2022 (Actual)
Study Completion Date
May 4, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ionis Pharmaceuticals, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine the safety, tolerability, and efficacy of IONIS-GHR-LRx subcutaneous (SC) injection as monotherapy in patients with acromegaly.
Detailed Description
This is a multi-center, open-label, randomized, Phase 2 study of IONIS-GHR-LRx in up to 40 participants with acromegaly. Participants will be randomized to 1 of 3 treatment groups to receive a single dose of IONIS GHR-LRx monthly for 73 weeks. At the end of 73 weeks, participants will enter a 14-week post-treatment (PT) evaluation period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acromegaly
Keywords
acromegaly, IONIS-GHR-LRx
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
34 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IONIS-GHR-LRx Dose 1
Arm Type
Experimental
Arm Description
Single dose of IONIS-GHR-LRx Dose 1 will be administered by SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3).
Arm Title
IONIS-GHR-LRx Dose 2
Arm Type
Experimental
Arm Description
Single dose of IONIS-GHR-LRx Dose 2 will be administered by SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3).
Arm Title
IONIS-GHR-LRx Dose 3
Arm Type
Experimental
Arm Description
Single dose of IONIS-GHR-LRx Dose 3 will be administered by SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3).
Intervention Type
Drug
Intervention Name(s)
IONIS-GHR-LRx
Intervention Description
IONIS-GHR-LRx will be administered by SC injection.
Primary Outcome Measure Information:
Title
Percent Change From Baseline in Insulin-like Growth Factor I (IGF-1) to Week 27
Time Frame
Up to Week 27
Secondary Outcome Measure Information:
Title
Percentage of Participants who Achieve Normalized IGF-1 Levels to Within 1.2 Times of Gender and Age Limits at Day 183 (Week 27)
Time Frame
At Week 27
Title
Percentage of Participants who Achieve Normalized IGF-1 Levels to Within 1.0 Times of Gender and Age Limits at Day 183 (Week 27)
Time Frame
At Week 27
Title
Change From Baseline in Serum IGF-1 Over Time
Time Frame
Up to approximately 80 weeks
Title
Percent Change From Baseline in Serum IGF-1 Over Time
Time Frame
Up to approximately 80 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males or females with a documented diagnosis of Acromegaly* who are 18 to 75 years old (inclusive) at the time of informed consent.
Have had pituitary surgery (e.g. transsphenoidal) unless there was a contraindication to surgery and are either acromegaly medical treatment naïve, or who had not taken any other acromegaly medications prior to the screening visit as outlined below
bromocriptine: 2 weeks
cabergoline: 4 weeks
quinagolide: 4 weeks
octreotide daily injection (SC) or oral formulation: 4 weeks
pegvisomant: 4 weeks
octreotide LAR: 3 months
pasireotide LAR: 4 months
lanreotide (all formulations): 3 months
At Screening, serum IGF-1 (performed at the central lab) between 1.3 to 5 × ULN, inclusive, adjusted for age and sex.
Females must be non-pregnant and non-lactating, and either surgically sterile, post-menopausal, abstinent, or using 1 highly effective method of birth control
Exclusion Criteria:
Participants who received surgery for pituitary adenoma within the last 3 months before the trial, and/or planning to receive surgery during the trial
Participants who received radiotherapy for pituitary adenoma within the last 2 years before the trial, and/or planning to receive radiotherapy during the trial
Participants with a pituitary tumor that, per Investigator judgment, is worsening (e.g., either growing or at risk of compressing or abutting the optic chiasm or other vital structures) as assessed by pituitary/sellar MRI protocol at Screening or within 3 months of Screening. CT scan is allowed if MRI is contraindicated
Evidence of decompensated cardiac function per medical judgement and/or New York Heart Association (NYHA) Class 3 or 4
Clinical evidence of symptomatic hyperprolactinemia that would necessitate treatment
Symptomatic cholelithiasis, and/or choledocholithiasis
Facility Information:
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Palm Research Center Inc.
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89148
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Endocrinology Associates, Inc
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43201
Country
United States
Facility Name
Oregon Health & Science University (OHSU)
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
East-Tallinn Central Hospital
City
Tallinn
ZIP/Postal Code
10138
Country
Estonia
Facility Name
Tartu University Hospital
City
Tartu
ZIP/Postal Code
50406
Country
Estonia
Facility Name
Debreceni Egyetem Klinikai Kozpont
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
City
Roma
ZIP/Postal Code
00168
Country
Italy
Facility Name
Pauls Stradins Clinical University Hospital
City
Rīga
ZIP/Postal Code
LV-1002
Country
Latvia
Facility Name
Vaidoto Urbanaviciaus Individuali imone
City
Alytus
ZIP/Postal Code
63246
Country
Lithuania
Facility Name
Hospital of Lithuanian University of Health Sciences (LSMU) Kauno klinikos
City
Kaunas
ZIP/Postal Code
50161
Country
Lithuania
Facility Name
Zespol Oddzialow Chorob Wewnetrznych, Endokrynologii i Diabetologii
City
Warszawa
ZIP/Postal Code
03-242
Country
Poland
Facility Name
Uniwersytecki Szpital Kliniczny, im. Jana Mikulicza-Radeckiego we Wroclawiu,
City
Wrocław
ZIP/Postal Code
50-556
Country
Poland
Facility Name
Centrum Badan Klinicznych Piotr Napora Lekarze Sp. p.
City
Wrocław
ZIP/Postal Code
51-162
Country
Poland
Facility Name
Centrul Medical Unirea Bucuresti, Endocrinologie
City
Bucharest
ZIP/Postal Code
060044
Country
Romania
Facility Name
I.M. Sechenov Moscow First State Medical University
City
Moscow
ZIP/Postal Code
119146
Country
Russian Federation
Facility Name
Clinical Center of Serbia
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Clinical Center of Vojvodina
City
Novi Sad
ZIP/Postal Code
21000
Country
Serbia
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study to Assess the Safety, Tolerability, and Efficacy of IONIS-GHR-LRx Administered in Patients With Acromegaly
We'll reach out to this number within 24 hrs