A Study to Evaluate the Safety and Efficacy of Paltusotine for the Treatment of Acromegaly (ACROBAT Evolve)

A Double-blind, Placebo-controlled, Randomized Withdrawal Study to Evaluate the Safety, Pharmacokinetics and Efficacy of CRN00808 in Patients With Acromegaly That Are Responders to Octreotide LAR or Lanreotide Depot (ACROBAT Evolve)

A Phase 2 double-blind, placebo-controlled, randomized withdrawal study is designed to evaluate the safety, efficacy, and pharmacokinetics of paltusotine (formerly CRN00808) in subjects with acromegaly that are responders to octreotide LAR or lanreotide depot.

Study Overview

• Status: Completed
• Conditions: Acromegaly
• Intervention / Treatment: Drug: Paltusotine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Curitiba, Brazil
    • CETI - Centro de Estudos em Terapias Inovadoras
  • São Paulo, Brazil
    • CPQuali Pesquisa Clínica
• Greece
  • Athens, Greece
    • General Hospital of Athens "Gennimatas"
• Hungary
  • Budapest, Hungary
    • Semmelweis University Faculty of Medicine
  • Pécs, Hungary
    • University of Pecs Medical School
• New Zealand
  • Wellington, New Zealand
    • Endocrine, Diabetes and Research Centre, Wellington Hospital
• Poland
  • Warsaw, Poland
    • The Centre of Postgraduate Medical Education
• Serbia
  • Belgrade, Serbia
    • Clinical Centre Serbia, Clinic for endocrinology, diabetes and metabolic diseases
• Slovakia
  • Ľubochňa, Slovakia
    • National Institute of Endocrinology and Diabetology
• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Texas
    • Dallas, Texas, United States, 10260
      • The Research Institute of Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male and female subjects 18 to 75 years of age
2. Confirmed diagnosis of acromegaly that is controlled on stable doses of octreotide LAR or lanreotide depot
3. Females must be non-pregnant and non-lactating, and either surgically sterile, post-menopausal, or using effective method(s) of birth control
4. Willing to provide signed informed consent

Exclusion Criteria:

1. Treatment naïve acromegaly subjects
2. Prior treatment with paltusotine
3. Pituitary surgery within 6 months prior to Screening or radiation therapy at any time prior to the study entry. Pituitary radiation therapy (within 3 to 4 years or more than 4 years prior to study entry) with recently documented elevated IGF-1 may be eligible.
4. History or presence of malignancy except adequately treated basal cell and squamous cell carcinomas of the skin within the past 5 years.
5. Use of any investigational drug within the past 30 days or 5 half-lives, whichever is longer
6. Positive test at Screening for HIV, hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCV-Ab) or has a history of a positive result
7. History of alcohol or substance abuse in the past 12 months
8. Any condition that in the opinion of the investigator would jeopardize the subject's appropriate participation in this study
9. Cardiovascular conditions or medications associated with prolonged QT or those which predispose subjects to heart rhythm abnormalities.
10. Subjects with symptomatic cholelithiasis
11. Subjects with clinically significant abnormal findings during the Screening Period, and any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardize the subject's safety or ability to complete the study
12. Subjects who have been taking the following prior medications: pegvisomant (within the last 3 months), dopamine agonists (within the last 3 months) and pasireotide LAR (within the last 6 months)
13. Subjects taking octreotide LAR at a dose higher than 40 mg or lanreotide depot at a dose higher than 120 mg
14. Subjects who usually take octreotide LAR or lanreotide depot less frequently than every 4 weeks (e.g. every 6 weeks or 8 weeks)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo, capsules, once daily by mouth
Experimental: Paltusotine	Drug: Paltusotine; Paltusotine, capsules, once daily by mouth; Other Names: CRN00808

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder Criteria Was Based on the Mean of Two Consecutive Insulin-like Growth Factor-1 [IGF-1] Measurements ≤ULN at Week 13	Proportion of subjects who meet responder criteria (based on the mean of two consecutive IGF-1 measurements ≤ upper limit of normal [ULN])	13 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in IGF-1 Levels	Change in IGF-1 levels between RWP Baseline/Week 10 and Week 13	From Week 10 to Week 13
Change in Growth Hormone (GH) Levels	Change in growth hormone levels between RWP Baseline/Week 8 and Week 13	From Week 8 to Week 13
Change in Total ASD Score Between RWP Baseline/Week 10 and Week 13	Measured by total Acromegaly symptom diary (ASD) score from W10-W13. ASD is a sponsor-developed daily diary to assess important acromegaly symptoms from the patient perspective. It covers 7 symptoms (headache pain, joint pain, sweating, fatigue, weakness in legs, swelling, and numbness or tingling). Patients rate the severity of each experience in the past 24 hours on an 11-point numeric scale that ranges from 0 (no symptom) to 10 (worst symptom). A weekly average ASD score is calculated for each item as the sum of the item responses for a specific item over the course of the study week divided by the number of days on which the item was completed. The weekly average ASD total score is calculated by computing the sum of the weekly average item scores for the 7 items (total range from 0 to 70), where higher score = higher symptom severity.	From Week 10 to Week 13

Collaborators and Investigators

• Sponsor: Crinetics Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2019
• Primary Completion (Actual): July 15, 2020
• Study Completion (Actual): August 12, 2020

Study Registration Dates

• First Submitted: December 27, 2018
• First Submitted That Met QC Criteria: January 1, 2019
• First Posted (Actual): January 3, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 4, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Acromegaly; Paltusotine; ACROBAT; EVOLVE
• Additional Relevant MeSH Terms: Endocrine System Diseases; Bone Diseases; Musculoskeletal Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypothalamic Diseases; Hyperpituitarism; Pituitary Diseases; Bone Diseases, Endocrine; Acromegaly
• Other Study ID Numbers: CRN00808-02; 2018-001833-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No