Clinical trial NCT04522180: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acromegaly
Keywords: acromegaly
IONIS-GHR-LRx
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-08-21
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Males or females with a documented diagnosis of Acromegaly\* who are 18 to 75 years old (inclusive) at the time of informed consent.
2. 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
3. At Screening, serum IGF-1 (performed at the central lab) between 1.3 to 5 × ULN, inclusive, adjusted for age and sex.
4. 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:

1. Participants who received surgery for pituitary adenoma within the last 3 months before the trial, and/or planning to receive surgery during the trial
2. Participants who received radiotherapy for pituitary adenoma within the last 2 years before the trial, and/or planning to receive radiotherapy during the trial
3. 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
4. Evidence of decompensated cardiac function per medical judgement and/or New York Heart Association (NYHA) Class 3 or 4
5. Clinical evidence of symptomatic hyperprolactinemia that would necessitate treatment
6. Symptomatic cholelithiasis, and/or choledocholithiasis

Primary outcomes:
measure: Percent Change in Insulin-like Growth Factor I (IGF-1) From Baseline to Week 27
timeFrame: Baseline to Week 27
Secondary outcomes:
measure: Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.2 Times Gender and Age Limits at Day 183 (Week 27)
timeFrame: At Week 27
measure: Percentage of Participants Who Achieve Normalized IGF-1 Levels to Within 1.0 Times Gender and Age Limits at Day 183 (Week 27)
timeFrame: At Week 27
measure: Change From Baseline in Serum IGF-1 Over Time
timeFrame: Up to approximately 80 weeks
measure: Percent Change From Baseline in Serum IGF-1 Over Time
timeFrame: 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
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Las Vegas
country: United States
facility: Palm Research Center Inc.
state: Nevada
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Endocrinology Associates, Inc
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University (OHSU)
state: Oregon
city: Tallinn
country: Estonia
facility: East-Tallinn Central Hospital
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
city: Rīga
country: Latvia
facility: Pauls Stradins Clinical University Hospital
city: Alytus
country: Lithuania
facility: Vaidoto Urbanaviciaus Individuali imone
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences (LSMU) Kauno klinikos
city: Warszawa
country: Poland
facility: Zespol Oddzialow Chorob Wewnetrznych, Endokrynologii i Diabetologii
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny, im. Jana Mikulicza-Radeckiego we Wroclawiu,
city: Wrocław
country: Poland
facility: Centrum Badan Klinicznych Piotr Napora Lekarze Sp. p.
city: Bucharest
country: Romania
facility: Centrul Medical Unirea Bucuresti, Endocrinologie
city: Moscow
country: Russian Federation
facility: I.M. Sechenov Moscow First State Medical University
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Novi Sad
country: Serbia
facility: Clinical Center of Vojvodina
Study officials:
References: