A 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.

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
    • St. 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
    • City of Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research
    • Kansas City, Missouri, United States, 64111
      • Clinical Research Consultants, LLC
  • 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 Weekly Average Pain Intensity Assessed by the Numeric Pain Rating Scale (NPRS) at Week 12	The NPRS of pain intensity is an 11-point numeric scale, ranging from 0 (representing no pain at all) to 10 (representing the worst pain imaginable). The participants were asked to select a whole number (0 to 10) that best indicates the intensity of his/her neuropathic pain in the past 24 hours. The weekly average score of NPRS was defined as the sum of non-missing daily scores divided by the number of days with non-missing scores for that week. Negative change from baseline indicates decreased pain intensity.	Baseline, Week 12
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) During and Following the Treatment Period	An adverse event (AE) was any unfavorable and unintended sign (including any CS abnormal laboratory test result), symptom, or disease temporally associated with use of the study drug, whether or not it is considered to be study drug related. An SAE was any untoward medical occurrence that at any dose resulted in death, in the view of Investigator, placed participant at immediate risk of death, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a birth defect. AEs that presented, or worsened in intensity or frequency, following the initiation of study treatment were categorized as TEAEs.	From the first dose of study drug up to end of follow-up period (up to 16 weeks)
Number of Participants With Clinically Significant Abnormalities in Physical Examinations	Clinically significant abnormalities in physical examinations were based on investigator discretion.	From the first dose of study drug up to end of follow-up period (up to 16 weeks)
Number of Participants With Potential Clinically Significant Abnormalities in Vital Sign Parameters	Vital sign parameters included temperature, pulse rate systolic blood pressure, diastolic blood pressure, and respiratory rate. As pre-specified in protocol, the criteria for determining potentially clinically relevant abnormalities in vital signs included: temperature < 36.0 and > 38.0 degrees Celsius (c), pulse rate < 60 and > 100 beats per minute (bpm), systolic blood pressure < 90, > 140 and > 160 millimeters of mercury (mmHg), diastolic blood pressure < 50, > 90 and > 100 mmHg, weight (7% or more increase from baseline, 7% or more decrease from baseline) and respiratory rate < 12 and > 20 breaths per minute. The categories with at least one participant with clinically significant vital sign abnormalities are reported.	From the first dose of study drug up to end of follow-up period (up to 16 weeks)
Number of Participants With Shift From Baseline in Clinically Significant Abnormalities in Electrocardiogram (ECG)	Clinical significance of abnormalities in ECG was determined based on the investigator's discretion.	From the first dose of study drug up to end of follow-up period (up to 16 weeks)
Number of Participants With Shift From Baseline in Clinical Laboratory Measurement (Hematology Parameters)	Hematology parameters included hematocrit, hemoglobin, erythrocytes, leukocytes, neutrophils, lymphocytes, monocytes, basophils, eosinophils, platelets, mean corpuscular hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin concentration. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available. Here, shift to low indicated values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high postbaseline values. The categories with at least one participant with shift from baseline in these parameters are reported.	From the first dose of study drug up to end of follow-up period (up to 16 weeks)
Number of Participants With Shift From Baseline in Clinical Laboratory Measurement (Blood Chemistry Parameters)	Parameters included alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, choriogonadotropin beta, follicle stimulating hormone (FSH), estimated glomerular filtration rate (eGFR), ferritin, creatine kinase, blood urea nitrogen, creatinine, bilirubin(total and direct), alkaline phosphatase, amylase, lipase, sodium, potassium, calcium, phosphorus, uric acid, total protein, glucose, albumin, lactate dehydrogenase, magnesium, chloride, bicarbonate, and gamma-glutamyl transferase. These parameters were flagged as low, normal or high relative to parameter's normal range or as unknown if no result was available, by Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high values postbaseline. Categories with at least one participant with shift from baseline in these parameters are reported.	From the first dose of study drug up to end of follow-up period (up to 16 weeks)
Number of Participants With Shift From Baseline in Clinical Laboratory Measurement (Urinalysis)	Urinalysis included assessments of bacteria, Bilirubin, Calcium Oxalate Crystals, Choriogonadotropin Beta, Color, Erythrocytes, Glucose, Granular Casts, Hyaline Casts, Ketones, Leukocyte Esterase, Leukocytes, Nitrite, Occult Blood, Protein, red blood cells (RBC) Casts, Renal Epithelial Cells, Specific Gravity, Specimen Appearance, Squamous Epithelial Cells, Transitional Epithelial Cells, Triple Phosphate Crystals, Uric Acid Crystals, white blood cells (WBC) Casts and pH. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high postbaseline. The categories with at least one participant with shift from baseline in these parameters are reported.	From the first dose of study drug up to end of follow-up period (up to 16 weeks)
Number of Participants With Shift From Baseline in Clinical Laboratory Measurement (Coagulation Parameters)	Coagulation included assessments of prothrombin. The parameter was flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high postbaseline.	From the first dose of study drug up to end of follow-up period (up to 16 weeks)
Number of Participants With Clinically Significant Abnormality in Body Weight	Weight decrease was characterized by a decrease of ≥7% from baseline and weight increase was characterized by an increase of ≥7% from baseline.	From the first dose of study drug up to end of follow-up period (up to 16 weeks)

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	Responders is defined as participants with at least >=30% reduction in neuropathic pain from baseline in the NPRS average neuropathic pain intensity at Week 12 and were analysed using a logistic regression. 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 was asked to select a whole number (0 to 10) that best indicates the intensity of his/her neuropathic pain in the past 24 hours. Lower scores indicate less pain.	Baseline, Week 12
Number of Participants Who Achieved at Least a >=50% Decrease From Baseline in the Average NPRS Score at Week 12	Responder is defined as participants with at least >=50% reduction in neuropathic pain from baseline in the NPRS average neuropathic pain intensity 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 was asked to select a whole number (0 to 10) that best indicates the intensity of his/her neuropathic pain in the past 24 hours.	Baseline, Week 12
Number of Participants Using Rescue Medications During the Treatment Period	Rescue medication for diabetic peripheral neuropathic pain (DPNP) is in addition to standard of care medication (gabapentin, pregabalin or duloxetine) for DPNP. Rescue medication is intended to treat temporary elevations in a participant's DPNP and is intended to be used occasionally and not meant to be used for prolonged periods of time.	Up to Week 12
Amount of Rescue Medications Used During the Treatment Period	The amount of rescue medication used per day during the 12-week treatment period was calculated as the total dosage recorded divided by total days of study drug exposure during the treatment period.	Up to Week 12
Time to First Occurrence of Rescue Medication Use	Time to first occurrence of rescue medication use was defined as the time from first randomized dose to the first date of rescue medication use recorded in e-diary during the 12-week treatment period. If a participant withdraws from the study prior to week 12 and the participant did not take any rescue medication, then the participant will be censored on the last day in the study.	Up to Week 12
Change From Baseline in the Weekly Average of 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 was completed daily by participants upon waking, preferably in the morning, to accurately capture variability in sleep interference due to pain, thus minimizing recall bias. Using the e-diary, participants assessed how neuropathic 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 indicating less pain interference during sleep. The weekly average score of DSIS was defined as the sum of non-missing daily scores divided by the number of days with non-missing scores for that week. A negative change from baseline indicates decreased interference in sleep due to pain.	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: October 13, 2022
• First Submitted That Met QC Criteria: May 31, 2023
• First Posted (Actual): June 8, 2023

Study Record Updates

• Last Update Posted (Estimated): December 15, 2025
• Last Update Submitted That Met QC Criteria: November 27, 2025
• Last Verified: November 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