A Study to Assess the Safety, Tolerability, and Efficacy of IONIS-GHR-LRx Administered in Patients With Acromegaly
- Conditions
- Acromegaly
- Interventions
- Drug: GHR-LRX
- Registration Number
- NCT04522180
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
The purpose of this study was to determine the safety, tolerability, and efficacy of IONIS-GHR-LRx subcutaneous (SC) injection as monotherapy in patients with acromegaly.
- Detailed Description
This was a multi-center, open-label, randomized, Phase 2 study of IONIS-GHR-LRx in up to 40 participants with acromegaly. Participants were randomized to 1 of 2 treatment groups to receive IONIS GHR-LRx monthly for 73 weeks. At the end of 73 weeks, participants entered a 14-week post-treatment (PT) evaluation period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 34
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description GHR-LRX 120 mg GHR-LRX Participants received GHR-LRX 120 mg subcutaneous (SC) injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3). GHR-LRX 160 mg GHR-LRX Participants received GHR-LRX 160 mg SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3).
- Primary Outcome Measures
Name Time Method Percent Change in Insulin-like Growth Factor I (IGF-1) From Baseline to Week 27 Baseline to Week 27 IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. Baseline of IGF-1 is defined as the average value of Screening and Day 1. A negative percent change from Baseline indicated improvement.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.2 Times Gender and Age Limits at Day 183 (Week 27) At Week 27 Normalized IGF-1 level is defined as the ratio of the serum IGF-1 level and the participant's upper limit of normal (ULN).
Change From Baseline in Serum IGF-1 Over Time Up to approximately 80 weeks IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. A negative change from baseline indicated improvement.
Percent Change From Baseline in Serum IGF-1 Over Time Baseline, Week 3, 5, 7, 9, 11, 13, 15, 17, 21, 25, 27, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73 IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. A negative percent change from Baseline indicated improvement.
Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.0 Times Gender and Age Limits at Day 183 (Week 27) At Week 27 Normalized IGF-1 level is defined as the ratio of the serum IGF-1 level and the participant's ULN.
Trial Locations
- Locations (22)
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Vaidoto Urbanaviciaus Individuali imone
🇱🇹Alytus, Lithuania
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
🇮🇹Milano, Italy
Pauls Stradins Clinical University Hospital
🇱🇻Rīga, Latvia
I.M. Sechenov Moscow First State Medical University
🇷🇺Moscow, Russian Federation
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Palm Research Center Inc.
🇺🇸Las Vegas, Nevada, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Endocrinology Associates, Inc
🇺🇸Columbus, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Oregon Health & Science University (OHSU)
🇺🇸Portland, Oregon, United States
Tartu University Hospital
🇪🇪Tartu, Estonia
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
East-Tallinn Central Hospital
🇪🇪Tallinn, Estonia
Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
🇮🇹Roma, Italy
Hospital of Lithuanian University of Health Sciences (LSMU) Kauno klinikos
🇱🇹Kaunas, Lithuania
Zespol Oddzialow Chorob Wewnetrznych, Endokrynologii i Diabetologii
🇵🇱Warszawa, Poland
Centrum Badan Klinicznych Piotr Napora Lekarze Sp. p.
🇵🇱Wrocław, Poland
Centrul Medical Unirea Bucuresti, Endocrinologie
🇷🇴Bucharest, Romania
Clinical Center of Serbia
🇷🇸Belgrade, Serbia
Uniwersytecki Szpital Kliniczny, im. Jana Mikulicza-Radeckiego we Wroclawiu,
🇵🇱Wrocław, Poland
Clinical Center of Vojvodina
🇷🇸Novi Sad, Serbia