AN OPEN LABEL, LONG-TERM EXTENSION STUDY TO EVALUATE THE SAFETY AND EFFICACY OF CRN00808 IN SUBJECTS WITH ACROMEGALY (ACROBAT ADVANCE)
- Conditions
- Acromegaly is typically caused by a growth hormone (GH) secreting tumor in the pituitary. Excess GH secretion results in excess secretion of insulin-like growth factor-1 (IGF-1) from the liver, which causes bone overgrowth, organ enlargement, and changes in glucose and lipid metabolism. The symptoms of acromegaly include abnormal growth of hands and feet and changes in shape of the bones that result in alteration of facial features.MedDRA version: 20.0Level: PTClassification code 10000599Term: AcromegalySystem Organ Class: 10014698 - Endocrine disordersTherapeutic area: Diseases [C] - Hormonal diseases [C19]
- Registration Number
- EUCTR2019-002193-31-HU
- Lead Sponsor
- Crinetics Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 135
1. Subjects who have completed Crinetics Phase 2 studies CRN00808-02 or CRN00808-03 within
12 months prior to Screening or subjects with uncontrolled acromegaly who are not being treated
with acromegaly medications:
a. Group 1: Subjects who are not currently enrolled in CRN00808-02 or CRN00808-03, but
have completed CRN00808-02 or CRN00808-03 within 12 months and now have
resumed standard acromegaly medications;
b. Group 2a: Subjects who are completing studies CRN00808-02 or CRN00808-03 and
have not resumed standard acromegaly medication;
Group 2b: Subjects who are defined as completers of studies CRN00808-02 or
CRN00808-03 by receiving a rescue injection of long acting somatostatin agonist during
the Follow-up Period of the parent studies;
c. Group 3: Subjects with uncontrolled acromegaly who are not being treated with
acromegaly medications. These subjects will be recruited de novo at investigative sites.
These subjects must be medically stable males or females aged 18 to 75 inclusive with at
least one elevated IGF-1 level documented during the Screening Period. Documentation
of a pituitary tumor and elevated IGF-1 (e.g., >ULN) should be available to confirm the
initial diagnosis of acromegaly. Subjects who have had pituitary surgery must have had
surgery 3 or more months prior to Screening. Use of long acting somatostatin agonists is
not allowed within 3 months prior to Screening. Use of dopamine agonists, short acting
somatostatin agonists, or pegvisomant is not allowed within 1 month prior to screening
2. Subjects with adrenal insufficiency must be on adequate adrenal replacement therapy at the time
of Screening as determined by the investigator;
3. If the subject is female, she must be of non-childbearing potential (defined as either surgically
sterilized [i.e., hysterectomy, bilateral salpingectomy, or bilateral oophorectomy] or at least 1 year
of amenorrhea) OR must agree to one of the following from Screening until 28 days following the
last dose of study medication:
Complete abstinence from intercourse of reproductive potential. Abstinence is an acceptable
method of contraception only when it is in line with the subject’s preferred and usual lifestyle.
Or
Consistent and correct use of 1 of the following highly effective contraception methods of birth
control i.e., intrauterine device (IUD) with a failure rate of <1% per year, tubal sterilization,
vasectomy in the male partner (provided that the partner is the sole sexual partner and had
confirmation of surgical success 3 months after procedure). Should female subjects wish to use a
hormonally-based method; use of a male condom by the female subject’s male partner is required.
Subjects who utilize a hormonal contraceptive as one of their birth control methods must have
used the same method for at least 3 months prior to study dosing. Hormonally-based
contraceptives permitted for use in this protocol are as follows, oral contraceptives (either
combined or progesterone only), injectable progesterone, implants of levonorgestrel, transdermal
contraceptive patch, contraceptive vaginal ring.
4. If the subject is male, the subject must use a condom, or his female partner of childbearing
potential must use an effective form of contraception as described above, from the beginning of Screening to the last study visit. Male subjects must also agree not to donate sperm for the
duration of the study and until at least 3 months after the last dose of the study medication;
5. Subjects must b
Gp 1 & Gp 3 -1st ten are listed and the remaining 12 (22 total) are given in the protocol:
1. Clinically significant concomitant disease including: CV disease; moderate or severe renal insufficiency,significant liver disease (including cirrhosis) at Screening;
2. Pituitary radiation treatment at any time (Gp 3) or since completing in study CRN00808-02/03 (Gp 1);
3. Myocardial infarction, cardiac surgery revascularization ,cerebrovascular accident or stroke, or transient ischemic attack. Syncope or marked presyncope that is unexplained or related to cardiovascular disease within the last 5 years;
4. Any of: cardiac arrest or long QT syndrome, evidence for a familial sudden death syndrome, hemodynamically significant cardiac valvulopathy, greater than Canadian Cardiovascular Society Class 1 angina pectoris or unstable angina, greater than NY Heart Association Class 1 CHF, ongoing episodes of symptomatic bradycardia, known history of sustained ventricular tachycardia, hemodynamically significant pulmonary arterial hypertension; uncontrolled symptomatic supraventricular tachycardia, uncontrolled atrial fibrillation type 2 second degree, or third degree atrioventricular block;
5. Based on Holter monitor performed during the Screening Period: Symptomatic bradycardia, type 2 second degree, or third degree atrioventricular block, pause >3 sec, sustained ventricular or supraventricular tachycardia, previously undiagnosed paroxysmal atrial fibrillation, or torsades depointes;
6. Supine systolic blood pressure >150 mmHg and/or supine diastolic blood pressure >95 mmHg at Screening (if the initial measurement is out of range, may be repeated 2 more times after 15 min and exclusion will be based on the average of the 3 measurements);
7. Resting (+ 10 minutes) palpated pulse rate <50 bpm or >105 bpm at Screening. If either of these criteria are met, the assessment should be repeated 2 more times and the average should be used to determine the subject's eligibility;
8. Receiving medications known to cause heart rate slowing (beta-blockers, verapamil, diltiazem, or ivabradine) if resting heart rate is <60 bpm during Screening;
9. Corrected QT interval by Fredericia formula (QTcF) interval >450 msec (or QTc >480 msec in the presence of a bundle branch block) or PR interval >240 msec at Screening based on a central reading of an average of 3 (ECGs) each separated in time by 1 to 3 minutes after rested supine for 5 minutes;
10. Medications associated with torsades de pointes within 2 weeks of study medication dosing
All Subjects:
1. Clinically significant abnormal findings/medical/lab during the Screening Period, that in the opinion of the investigator, might jeopardize subject safety or ability to complete the study;
2. Compression of the optic chiasm causing any visual field defect or symptom associated with tumor compression;
3. Pregnant or lactating;
4. Known history of (within 12 months), or current alcohol or drug abuse;
5. Any mental condition which the nature, scope, and possible consequences of the study are not understood, evidence of poor compliance with medical instructions;
6. Known allergy, hypersensitivity to any of the test materials or related compounds;
7. Employee or immediate family member of an employee of Crinetics;
8. Investigational drug (other than CRN00808) in any prior clinical study within 30 days or 5 half-lives (whichever is longer) prior to Screening.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: This study is designed ito evaluate the long-term safety and tolerability of CRN00808 in acromegaly subjects; to evaluate the efficacy of CRN00808 in acromegaly patients.;Secondary Objective: Not Applicable;Primary end point(s): Primary endpoint:<br>The primary endpoint is the incidence of treatment-emergent AEs (TEAEs) throughout the study. <br>;Timepoint(s) of evaluation of this end point: study duration<br>
- Secondary Outcome Measures
Name Time Method