A Phase 2 Study of RTA 901 (BIIB143) in Participants With Diabetic Peripheral Neuropathic Pain (CYPRESS)

A Phase 2 Study to Evaluate the Safety and Efficacy of RTA 901 in Patients With Diabetic Peripheral Neuropathic Pain

This is a 2-part, randomized, placebo-controlled, double-blind, Phase 2 study to evaluate the safety, tolerability, efficacy, and pharmacokinetics (PK) of RTA 901 in qualified participants with Diabetic Peripheral Neuropathic Pain (DPNP). Each study part will be randomized into 3 treatment arms; 2 different doses of RTA 901 and RTA 901-maching placebo. The doses of RTA 901 in Part 2 will be selected based on the Exposure-Response (E-R) analyses of data from Part 1. A total of 384 participants will be randomized in this study. Each part will have 192 participants, with 64 participants randomized 1:1:1 to each treatment arm.

The duration of each part of the study will be approximately 20 weeks, including a Screening period of up to 2 weeks, a Run-in-period of 2 weeks, a Treatment period of 12 weeks, and a Follow-up period of 4 weeks. All participants in Part 1 and Part 2 of the study will follow the same visit and assessment schedule. Eligibility will be assessed during the Screening and Run-in-periods.

Study Overview

• Status: Terminated
• Conditions: Diabetic Peripheral Neuropathic Pain
• Intervention / Treatment: Drug: RTA 901; Drug: RTA 901-Matching Placebo

Detailed Description

Study Sponsor, originally Reata Pharmaceuticals, Inc., is now Reata Pharmaceuticals, Inc., a wholly owned subsidiary of Biogen.

• Study Type: Interventional
• Enrollment (Actual): 209
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Centricity Research Phoenix Multispecialty
    • Phoenix, Arizona, United States, 85053
      • Arizona Research Center
  • California
    • Canoga Park, California, United States, 91303
      • Hope Clinical Research, Inc.
    • Fresno, California, United States, 93720
      • Valley Research - Trials
    • Los Angeles, California, United States, 90048
      • Clinical Research Institute
    • San Diego, California, United States, 92120
      • Acclaim Clinical Research
    • San Francisco, California, United States, 94102
      • Optimus Medical Group
    • Whittier, California, United States, 90606
      • PIH Health Whittier Hospital
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Denver Endocrinology Diabetes and Thyroid Center PC
    • Wheat Ridge, Colorado, United States, 80033
      • Paradigm Clinical Research
  • Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida, Inc.
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida Inc
    • Jacksonville, Florida, United States, 32204
      • East Coast Institute for Research, LLC
    • Lake City, Florida, United States, 32055
      • Multi Specialty Research Associates, LLC
    • Lake Worth, Florida, United States, 33460
      • 3 Sync LLC
    • Miami, Florida, United States, 33126
      • Finlay Medical Research
    • Miami, Florida, United States, 33165
      • New Horizon Research Center
    • Miami Lakes, Florida, United States, 33016
      • Floridian Clinical Research
    • Saint Petersburg, Florida, United States, 33709
      • IMA Clinical Research, PC
    • Sunrise, Florida, United States, 33013
      • 3 Sync LLC
    • Tampa, Florida, United States, 33606
      • Clinical Research of West Florida, Inc.
    • Tampa, Florida, United States, 33603
      • Genesis Clinical Research
    • Tampa, Florida, United States, 33615
      • VICIS Clinical Research
    • Tampa, Florida, United States, 33607
      • Baycare Clinical Research
    • Winter Park, Florida, United States, 32789
      • Conquest Research, LLC
    • Winter Park, Florida, United States, 32789
      • Clinical Site Partners, Orlando
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • AGILE Clinical Research Trials, LLC
    • Canton, Georgia, United States, 30114
      • East Coast Institute for Research, LLC
    • Columbus, Georgia, United States, 31904
      • Centricity Research Columbus Endocrinology
    • Macon, Georgia, United States, 31210
      • East Coast Institute for Research, LLC
  • Illinois
    • Peoria, Illinois, United States, 61606
      • Methodist Medical Center of Illinois
  • Indiana
    • Evansville, Indiana, United States, 47714
      • MediSphere Medical Research Center, LLC
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Integrated Clinical Trial Services, Inc.
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research
    • Metairie, Louisiana, United States, 70006
      • Tandem Clinical Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials, LLC
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Practices & Research, LLC
  • Michigan
    • Sterling Heights, Michigan, United States, 48126
      • Revival Research Institute, LLC.
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Clinical Research Consultants, LLC
    • Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Velocity Clinical Research, Inc.
    • Norfolk, Nebraska, United States, 68510
      • Velocity Clinical Research, Inc.
  • Nevada
    • Henderson, Nevada, United States, 89074
      • Las Vegas Endocrinology
    • Las Vegas, Nevada, United States, 89109
      • Excel Clinical Research
    • Las Vegas, Nevada, United States, 89106
      • Jubilee Clinical Research Inc
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03801
      • ActivMed Practices & Research, LLC
  • New York
    • New York, New York, United States, 10032
      • Columbia University
    • Staten Island, New York, United States, 10314
      • Richmond Behavioral Associates
  • North Carolina
    • Fayetteville, North Carolina, United States, 28303
      • Carolina Institute for Clinical Research, LLC
  • Ohio
    • Canton, Ohio, United States, 44718
      • Diabetes & Endocrinology Associates of Stark County, Inc.
    • Cincinnati, Ohio, United States, 45242
      • Velocity Clinical Research, Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43215
      • Remington-Davis, Inc.
    • Dayton, Ohio, United States, 45432
      • META Medical Research Institute
  • Rhode Island
    • East Greenwich, Rhode Island, United States, 68510
      • Velocity Clinical Research, Providence
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Notus Clinical Research
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • WR-Clinsearch, LLC
    • Tullahoma, Tennessee, United States, 37388
      • Trinity Clinical Research LLC
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
    • Beaumont, Texas, United States, 77701
      • REX Clinical Trials, LLC
    • Dallas, Texas, United States, 75230
      • Zenos Clinical Research
    • Forney, Texas, United States, 75126
      • Care United Research, LLC
    • Fort Worth, Texas, United States, 76053
      • Diabetes and Thyroid Center of Fort Worth
    • Houston, Texas, United States, 77043
      • Biopharma Informatic, LLC
    • Houston, Texas, United States, 77079
      • Endocrine Ips, Pllc
    • Houston, Texas, United States, 77030
      • Nerve And Muscle Center Of Texas
    • Houston, Texas, United States, 77089
      • Amir A Hassan, MD, PA
    • Kingwood, Texas, United States, 77339
      • 3 Sync LLC
    • Lewisville, Texas, United States, 75057
      • Epic Clinical Research
    • Pearland, Texas, United States, 77584
      • Shadow Creek Medical Clinic
    • San Antonio, Texas, United States, 78230
      • VIP Trials
    • San Antonio, Texas, United States, 78229
      • Diabetes & Glandular Disease Clinic, P.A.
  • Utah
    • West Jordan, Utah, United States, 84088
      • Velocity Clinical Research, Salt Lake City
  • Washington
    • Renton, Washington, United States, 98057
      • Rainier Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Run-in Inclusion Criteria:

• Diagnosis of type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) at least 1 year prior to Screening
• Clinical diagnosis of DPNP defined as symptomatic distal symmetric polyneuropathy (secondary to diabetes) in the lower extremities, which may include symptoms of pain that is burning, lancinating, tingling, or shooting (electric shock-like). Pain in the lower extremities may occur with paresthesia or dysesthesia (unpleasant sensations of burning). Neuropathic pain may be accompanied by an exaggerated response to painful stimuli (hyperalgesia) and pain evoked by light touch or contact, eg, with socks, shoes, and bedclothes (allodynia);
• NPRS pain intensity score ≥ 4 on an 11-point scale at Screening
• A score ≥ 2.5 on the Michigan Neuropathy Screening Instrument (MNSI) Part B

Run-in Exclusion Criteria:

• Has neuropathy from a cause other than T1DM or T2DM
• Has a condition other than DPNP that could confound the assessment of pain (eg, fibromyalgia or regional pain caused by lumbar or cervical compression);
• Diabetic foot ulceration or infection within 90 days prior to Screening
• Prior participation in a study with RTA 901;

NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 RTA 901 Dose 1; Participants will receive study drug, once daily (QD), during the 2-week Run-in Period. Following randomization, the participants will receive a dose of RTA 901, QD, for a 12-week treatment duration.	Drug: RTA 901; Administered as specified in the treatment arm.; Other Names: BIIB143; Cemdomespib
Experimental: Part 1 RTA 901 Dose 2; Participants will receive study drug, QD, during the 2-week Run-in Period. Following randomization, the participants will receive a dose of RTA 901, QD, for a 12-week treatment duration.	Drug: RTA 901; Administered as specified in the treatment arm.; Other Names: BIIB143; Cemdomespib
Placebo Comparator: Part 1 RTA 901-Matching Placebo; Participants will receive study drug, QD, during the 2-week Run-in Period. Following randomization, the participants will receive a dose of RTA 901-matching placebo, QD, for a 12-week treatment duration.	Drug: RTA 901-Matching Placebo; Administered as specified in the treatment arm.
Experimental: Part 2 RTA 901 Dose 1; Participants will receive study drug, QD, during the 2-week Run-in Period. Following randomization, the participants will receive a dose of RTA 901, QD, for a 12-week treatment duration.	Drug: RTA 901; Administered as specified in the treatment arm.; Other Names: BIIB143; Cemdomespib
Experimental: Part 2 RTA 901 Dose 2; Participants will receive study drug, QD, during the 2-week Run-in Period. Following randomization, the participants will receive a dose of RTA 901, QD, for a 12-week treatment duration.	Drug: RTA 901; Administered as specified in the treatment arm.; Other Names: BIIB143; Cemdomespib
Placebo Comparator: Part 2 RTA 901-Matching Placebo; Participants will receive study drug, QD, during the 2-week Run-in Period. Following randomization, the participants will receive a dose of RTA 901-matching placebo, QD, for a 12-week treatment duration.	Drug: RTA 901-Matching Placebo; Administered as specified in the treatment arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Average Daily Pain Intensity as Assessed by the Numeric Pain Rating Scale (NPRS) at Week 12	The NPRS of pain intensity is a numeric scale, ranging from 0 (representing no pain at all) to 10 (representing the worst pain imaginable). The participant will select a whole number (0 to 10) that best indicates the intensity of his/her pain in the past 24 hours. Lower scores indicate less pain.	Baseline, Week 12
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During and Following the Treatment Period		From the first day of dosing up to end of follow-up period (Week 16)
Number of Participants With Clinically Significant Abnormality in Physical Examinations		Baseline up to Week 16
Number of Participants With Clinically Significant Abnormality in Vital Sign		Baseline up to Week 16
Number of Participants With Clinically Significant Abnormality in Electrocardiogram (ECG)		Baseline up to Week 16
Number of Participants With Clinically Significant Abnormality in Clinical Laboratory Measurement		Baseline up to Week 16
Number of Participants With Clinically Significant Abnormality in Body Weight		Baseline up to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants who Achieved at Least a 30% Decrease From Baseline in the Average NPRS Score at Week 12	The NPRS of pain intensity is a numeric scale, ranging from 0 (representing no pain at all) to 10 (representing the worst pain imaginable). The participant selects a whole number (0 to 10) that best indicates the intensity of his/her pain in the past 24 hours. Lower scores indicate less pain.	Week 12
Number of Participants who Achieved at Least a 50% Decrease From Baseline in the Average NPRS Score at Week 12	The NPRS of pain intensity is a numeric scale, ranging from 0 (representing no pain at all) to 10 (representing the worst pain imaginable). The participant will select a whole number (0 to 10) that best indicates the intensity of his/her pain in the past 24 hours. Lower scores indicate less pain.	Week 12
Number of Participants Using Rescue Medications During the Treatment Period		Up to Week 12
Amount of Rescue Medications Used During the Treatment Period		Up to Week 12
Duration of Rescue Medications Used During the Treatment Period		Up to Week 12
Change From Baseline in the Average Daily Sleep Interference Scale (DSIS) score at Week 12	DSIS is a participant reported outcome that was developed to quantify sleep interference due to pain. The DSIS will be completed daily by participants upon waking (3-minute self-administered questionnaire), preferably in the morning, to accurately capture variability in sleep interference due to pain, thus minimizing recall bias. Using the e-diary, participants will assess how pain has interfered with their sleep during the past 24 hours. This score ranges from 0 to 10; 0 representing no interference with sleep to 10 representing complete inability to sleep. Lower score indicates less pain interference during sleep.	Baseline, Week 12

Collaborators and Investigators

• Sponsor: Reata, a wholly owned subsidiary of Biogen
• Investigators: Study Director: Medical Director, Biogen

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2023
• Primary Completion (Actual): November 15, 2024
• Study Completion (Actual): November 15, 2024

Study Registration Dates

• First Submitted: March 24, 2025
• First Submitted That Met QC Criteria: March 24, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 24, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: RTA 901
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Endocrine System Diseases; Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Diabetes Mellitus; Diabetes Complications; Neuralgia; Diabetic Neuropathies
• Other Study ID Numbers: 297DP201; 901-C-2102 (Other Identifier: Reata, a wholly owned subsidiary of Biogen)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

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