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

December 1, 2023 updated by: Pfizer

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Assess the Effect of Oral Temanogrel on Digital Blood Flow in Subjects With Raynaud's Phenomenon Secondary to Systemic Sclerosis

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The study will be conducted in 2 stages: Stage A and Stage B. In both stages, participants will be equally randomized in a double-blind manner to a 3-period crossover treatment sequence. Separate cohorts of participants will participate in each stage. In Stage A, participants will be treated with two dose levels of temanogrel and placebo. Doses in Stage B will be determined based on the results of Stage A.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
13

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Bath, United Kingdom, BAI 3NG
        • Royal United Hospitals Bath
      • Salford, United Kingdom, M6 8HD
        • Salford Royal Hospital
    • Scotland
      • Dundee, Scotland, United Kingdom, DD1 9SY
        • Ninewells Hospital & Medical School
  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Yale University
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Johns Hopkins Asthma and Allergy Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC Arthritis and Auotimmune Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Temanogrel (Stage A Dose 1)
Drug: Temanogrel
Participants will receive a single oral dose of temanogrel during the treatment visit.
Other Names:
  • APD791
Experimental: Temanogrel (Stage A Dose 2)
Drug: Temanogrel
Participants will receive a single oral dose of temanogrel during the treatment visit.
Other Names:
  • APD791
Placebo Comparator: Placebo (Stage A)
Drug: Placebo
Participants will receive a single oral dose of temanogrel matching placebo during the treatment visit.
Experimental: Temanogrel (Stage B Dose 1)
Drug: Temanogrel
Participants will receive a single oral dose of temanogrel during the treatment visit.
Other Names:
  • APD791
Experimental: Temanogrel (Stage B Dose 2)
Drug: Temanogrel
Participants will receive a single oral dose of temanogrel during the treatment visit.
Other Names:
  • APD791
Placebo Comparator: Placebo (Stage B)
Drug: Placebo
Participants will receive a single oral dose of temanogrel matching placebo during the treatment visit.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Digital Blood Flow Based on Rewarming Area Under the Curve (AUC) During Thirty Minutes Following a Cold Challenge
Time Frame: 30 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
Time Frame: 30 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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Maximum Reduction in Temperature Following a Cold Challenge Assessed With Infrared (IR) Thermography
Time Frame: 30 minutes following a cold challenge
IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. 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. 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
Maximum Reduction in Perfusion Temperature Following a Cold Challenge With Laser Speckle Contrast Imaging (LSCI)
Time Frame: 30 minutes following a cold challenge
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. LSCI 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 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
Maximum Recovery in Temperature Following a Cold Challenge Assessed With IR Thermography
Time Frame: 30 minutes following a cold challenge
IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. Changes in skin temperature at each visit were imaged IR thermography. 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. 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
Maximum Recovery in Perfusion Temperature Following a Cold Challenge Assessed With LSCI
Time Frame: 30 minutes following a cold challenge
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. LSCI was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. Changes in skin temperature at each visit were imaged using LSCI. LSCI therefore provides quantitative measures of blood flow within predefined region of interests (ROIs) as mean arbitrary perfusion units, pu. Higher values of pu 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
AUC During the Initial Two Minutes Following a Cold Challenge Assessed With IR Thermography
Time Frame: Initial 2 minutes following a cold challenge
AUC was defined as the area under the skin temperature curve. IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. 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. 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).
Initial 2 minutes following a cold challenge
Perfusion AUC During the Initial Two Minutes Following a Cold Challenge Assessed With LSCI
Time Frame: Initial 2 minutes following a cold challenge
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. LSCI 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. AUC was defined as the area under the skin temperature curve, based on the LSCI results. 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).
Initial 2 minutes following a cold challenge
Slope During the Initial 2 Minutes (120 Seconds) Following a Cold Challenge Assessed With IR Thermography
Time Frame: Initial 2 minutes following a cold challenge
IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. A cold challenge was conducted by immersing the hands in a temperature-controlled water bath (15 [+/- 1] degree celsius) for 60 seconds, followed by post-cold challenge digital blood flow assessments. Slope was calculated based on the changes in skin temperature imaged using LSCI and IR thermography during the initial 120 seconds following the cold challenge. 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).
Initial 2 minutes following a cold challenge
Perfusion Slope During the Initial 2 Minutes (120 Seconds) Following a Cold Challenge Assessed With LSCI
Time Frame: Initial 2 minutes following a cold challenge
A cold challenge was conducted by immersing the hands in a temperature-controlled water bath (15 [+/- 1] degree celsius) for 60 seconds, followed by post-cold challenge digital blood flow assessments. LSCI 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. Slope was calculated based on the changes in skin temperature imaged using LSCI during the initial 120 seconds following the cold challenge. 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).
Initial 2 minutes following a cold challenge
Time to Achieve 50 Percent (%) Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI
Time Frame: 30 minutes following a cold challenge
IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature, while LSCI was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. 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. If 50% recovery was not achieved, the recovery time was set to 30 minutes. 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
Time to Achieve 70 % Recovery From the Cold Challenge-Induced Reduction Assessed With IR Thermography and With LSCI
Time Frame: 30 minutes following a cold challenge
IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature, while LSCI was based on differences in the speckle pattern (occurring when laser light illuminates a tissue) due to movement of blood cells. 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. If 70% recovery was not achieved, the recovery time was set to 30 minutes. 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 From Predose to Post-dose in Room Temperature Values as Assessed With IR Thermography
Time Frame: 5 minutes pre-dose, 5 minutes post-dose
IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. Digital blood flow was assessed at each treatment visit at Predose for 5 minutes at room temperature, and at post-dose prior to cold challenge for 5 minutes at room 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).
5 minutes pre-dose, 5 minutes post-dose
Change From Predose to Post-dose in Room Temperature Perfusion Values as Assessed With LSCI
Time Frame: 5 minutes pre-dose, 5 minutes post-dose
Digital blood flow was assessed at each treatment visit at Predose for 5 minutes at room temperature, and at post-dose prior to cold challenge for 5 minutes at room temperature. LSCI 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 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).
5 minutes pre-dose, 5 minutes post-dose
Change From Predose to Post-dose in Distal Dorsal Difference (DDD), Assessed With IR Thermography
Time Frame: 5 minutes pre-dose, 5 minutes post-dose
The distal dorsal difference was defined as the difference in temperature between the dorsum and the finger, from pre dose of study treatment to post-dose. IR thermography was an indirect method for evaluation of blood flow based on imaging skin temperature. Digital blood flow was assessed at each treatment visit at Predose for 5 minutes at room temperature, and at postdose prior to cold challenge for 5 minutes at room 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).
5 minutes pre-dose, 5 minutes post-dose
Change From Predose to Post-dose in Distal Dorsal Difference (DDD) [Perfusion], Assessed With LSCI
Time Frame: 5 minutes pre-dose, 5 minutes post-dose
Digital blood flow was assessed at each treatment visit at Predose for 5 minutes at room temperature, and at postdose prior to cold challenge for 5 minutes at room temperature. LSCI 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 are considered better in the context of this trial. The distal dorsal difference was defined as the difference in perfusion temperature between the dorsum and the finger, from pre dose of study treatment to post-dose. 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).
5 minutes pre-dose, 5 minutes post-dose
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Time Frame: Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)
An adverse event was any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. TEAE was an AE that occurred after initiation of study treatment that was not present at the time of treatment start or an AE that increased in severity after the initiation of medication, if the event was present at the time of treatment start. SAE was an AE resulting in any of the following outcomes or considered medically significant: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or birth defect.
Day 1 of dose to maximum of 4 (+/-1) days after last dose (up to maximum of 22 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Arena is a wholly owned subsidiary of Pfizer

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 3, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 2, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 2, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 1, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 1, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 7, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 22, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 1, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • APD791-204
  • C5071001 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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