A Study to Assess the Effect of Oral Temanogrel on Digital Blood Flow in Adult Participants With Raynaud's Phenomenon Secondary to Systemic Sclerosis

NCT04915950 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: APD791-204C5071001
• Study Type: interventional
• Target: 13
• Locations: 2 countries
• Sites: 6

Brief Summary

The purpose of this study is to determine whether oral temanogrel improves digital blood flow in participants with Raynaud's phenomenon secondary to systemic sclerosis (SSc-RP) as a potential safe and effective treatment for symptoms associated with SSc-RP.

Conditions

Raynaud's Phenomenon Secondary to Systemic Sclerosis

Keywords

Raynaud's phenomenon; SSc-RP; Systemic sclerosis; SSc; Digital cold sensitivity; Digital blood flow; APD791; Temanogrel

Outcome Measures

Primary Outcomes (2)

• Change in Digital Blood Flow Based on Rewarming Area Under the Curve (AUC) During Thirty Minutes Following a Cold Challenge

  Area under the curve for rewarming of digital blood flow after 30 minutes following a cold challenge was assessed. Area under the curve was defined as the area under the skin temperature curve and rewarming was a delicate phase of therapeutic hypothermia (TH). A cold challenge was conducted by immersing the hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for one minute, followed by post-cold challenge digital blood flow assessments for 30 minutes. Rewarming was assessed by infrared (IR) thermography which was an indirect method for evaluation of blood flow based on imaging skin temperature. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).

  30 minutes following a cold challenge

• Change in Digital Blood Flow Based on Reperfusion AUC During the Thirty Minutes Following a Cold Challenge

  Area under the curve for reperfusion of digital blood flow after 30 minutes following a cold challenge was assessed. A cold challenge was conducted by immersing hands in a temperature-controlled water bath (15 \[+/- 1\] degree celsius) for one minute, followed by post-cold challenge digital blood flow assessments for 30 minutes. Reperfusion was assessed with laser speckle contrast imaging (LSCI) which was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. LSCI therefore provides quantitative measures of blood flow within predefined region of interests (ROIs) as mean arbitrary perfusion units, pu. Higher values of pu (and also pu\*seconds) are considered better in the context of this trial. Results presented were based on the average across all 8 fingers assessed (left index, left middle, left ring, left little, right index, right middle, right ring, right little).

  30 minutes following a cold challenge

Secondary Outcomes (15)

• Maximum Reduction in Temperature Following a Cold Challenge Assessed With Infrared (IR) Thermography

  30 minutes following a cold challenge

• Maximum Reduction in Perfusion Temperature Following a Cold Challenge With Laser Speckle Contrast Imaging (LSCI)

  30 minutes following a cold challenge

• Maximum Recovery in Temperature Following a Cold Challenge Assessed With IR Thermography

  30 minutes following a cold challenge

• Maximum Recovery in Perfusion Temperature Following a Cold Challenge Assessed With LSCI

  30 minutes following a cold challenge

• AUC During the Initial Two Minutes Following a Cold Challenge Assessed With IR Thermography

  Initial 2 minutes following a cold challenge

Study Arms (6)

Temanogrel (Stage A Dose 1)

EXPERIMENTAL

Drug: Temanogrel

Temanogrel (Stage A Dose 2)

EXPERIMENTAL

Drug: Temanogrel

Placebo (Stage A)

PLACEBO COMPARATOR

Drug: Placebo

Temanogrel (Stage B Dose 1)

EXPERIMENTAL

Drug: Temanogrel

Temanogrel (Stage B Dose 2)

EXPERIMENTAL

Drug: Temanogrel

Placebo (Stage B)

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Temanogrel DRUG

Participants will receive a single oral dose of temanogrel during the treatment visit.

Also known as: APD791

Temanogrel (Stage A Dose 1); Temanogrel (Stage A Dose 2); Temanogrel (Stage B Dose 1); Temanogrel (Stage B Dose 2)

Placebo DRUG

Participants will receive a single oral dose of temanogrel matching placebo during the treatment visit.

Placebo (Stage A); Placebo (Stage B)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Raynaud's phenomenon (defined as a history of digital cold sensitivity associated with color changes of cyanosis and pallor, with on average at least 5 attacks per week during the winter period) secondary to systemic sclerosis (SSc)
• Both men and women participants agree to use a highly effective method of birth control if the possibility of conception exists
• Body mass index 18.0 to 40.0 kilograms per square meter (kg/m\^2), inclusive

You may not qualify if:

• Active digital ulcer(s), recent history (within 3 months of Screening) of digital ulcers, or history of recurrent digital ulcerations that in the opinion of the Investigator increase the likelihood of developing a digital ulcer during the course of the study. Any history of gangrene, amputations, or other critical digital ischemic event
• Raynaud's phenomenon due to any cause other than SSc
• Severe gastrointestinal complications related to SSc that in the opinion of the Investigator could significantly affect study drug absorption
• History of gastrointestinal bleeding or active gastric or duodenal ulcers

Sponsors & Collaborators

• Pfizer: lead
• Arena is a wholly owned subsidiary of Pfizer: collaborator

Study Sites (6)

Yale University

New Haven, Connecticut, 06519, United States

Location

Johns Hopkins Asthma and Allergy Center

Baltimore, Maryland, 21224, United States

Location

UPMC Arthritis and Auotimmune Clinic

Pittsburgh, Pennsylvania, 15213, United States

Location

Ninewells Hospital & Medical School

Dundee, Scotland, DD1 9SY, United Kingdom

Location

Royal United Hospitals Bath

Bath, BAI 3NG, United Kingdom

Location

Salford Royal Hospital

Salford, M6 8HD, United Kingdom

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Raynaud Disease; Scleroderma, Systemic

Interventions

APD791

Condition Hierarchy (Ancestors)

Livedoid Vasculopathy; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Connective Tissue Diseases

Limitations and Caveats

This study was terminated early due to a business decision that was not due to any safety concerns. The number of participants was smaller than originally planned and only summary statistics were therefore generated for primary and secondary outcome measures.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquires@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2021
• First Posted: June 7, 2021
• Study Start: November 3, 2021
• Primary Completion: September 2, 2022
• Study Completion: September 2, 2022
• Last Updated: December 22, 2023
• Results First Posted: December 22, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share

Locations

US (3); GB (3)