Transthyretin AmyloidosisPhase 4NCT04963985
The Effect of Tafamidis on Transthyretin Stabilization, Safety, Tolerability and Efficacy in Transthyretin Amyloid Polyneuropathy Patients
A Phase 4 study testing Tafamidis Pill in people with Transthyretin Amyloidosis, run by Peking University Third Hospital at 1 site in China.
Trial summary
Transthyretin amyloid polyneuropathy (ATTR-PN) is a fatal illness resulting from autosomal dominantly inherited single-point mutations on the transthyretin gene. Tafamidis is a specific stabilizer of both variant and wild-type TTR. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Transthyretin Amyloidosis
- What is being tested?
- Tafamidis Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2021to 1 Jun 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- -
- Participants are eligible to be included in the study only if all of the following criteria apply:
- Age and Sex:
- Male or female participants between the ages of 18 and 80 years.
- Type of Participant and Disease Characteristics:
- Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations and other study procedures.
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- Participants have amyloid documented by biopsy in accordance with institutional site standard of care (Biopsy must have been performed within 5 years of enrollment).
- Participants must have a TTR mutation that is associated with ATTR-PN. (See Section 8.2.6.3 for further details).
- Participants have peripheral and/or autonomic neuropathy with a Karnofsky Performance Status ≥50 (refer to Appendix 5).
- Stages of disease according to symptom severity-stage I.
- Informed Consent:
- Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol.
Who cannot join
- -
- Participants are excluded from the study if any of the following criteria apply:
- Medical Conditions:
- Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
- Prior/Concomitant Therapy:
- Chronic use of non-protocol approved non-steroidal anti-inflammatory drugs (NSAIDs), defined as greater than 3-4 times/month. The following NSAID are allowed: acetylsalicylic acid, etodolac, ibuprofen, indomethacin, ketoprofen, nabumetone, naproxen, nimesulide, piroxicam, and sulindac.
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- Use of diflunisal, tauroursodeoxycholate, doxycycline or a TTR stabilizing agent, or other experimental interventions for familial amyloidosis within 30 days prior to the study entry and/or during study participation. Participants who are taking or who have previously taken tafamidis.
- Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of investigational product used in this study (whichever is longer).
- Diagnostic Assessments:
- Participant has primary (light chain) or secondary amyloidosis.
- If female, participant is pregnant or breast feeding, or plans to be pregnant or breast feeding in the next 18 months.
- Participant has received prior liver or any other organ except cornea transplantation.
- Participant has no recordable sensory threshold for vibration perception in both feet, as measured by CASE IV or participant requires significant assistance with ambulation or is wheel chair bound.
- Participants with positive results for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV).
- Participant has liver function test abnormalities: alanine transaminases (ALT) and/or aspartate transaminases (AST) >2 times upper limit of normal (ULN) that in the medical judgment of the investigator are due to reduced liver function or active liver disease.
- Participants with cardiomyopathy specific TTR mutations (Val122Ile, Leu111Met, Ile68Leu).
- Participant has a co-morbidity anticipated to limit survival to less than 18 months.
- Participant has other causes of sensorimotor neuropathy (B12 deficiency, Diabetes Mellitus, HIV treated with retroviral medications, thyroid disorders, alcohol abuse, Fabry disease, Lyme disease, sarcoidosis, Sjogren's Syndrome, Systemic Lupus Erythematosus, alcohol dependency, celiac disease, Chronic Inflammatory Demyelinating Polyneuropathy, and chronic inflammatory diseases).
- Other Exclusions:
- Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Peking University Third Hospital
Beijin
Dongsheng Fan, 13701023871, dsfan@sina.com
About this study
Transthyretin amyloid polyneuropathy (ATTR-PN) is a fatal illness resulting from autosomal dominantly inherited single-point mutations on the transthyretin gene.
Tafamidis is a specific stabilizer of both variant and wild-type TTR. Tafamidis binds to TTR at the thyroxine binding sites and inhibits TTR tetramer dissociation, the rate limiting step in the amyloidogenic process. The result disrupts the amyloid cascade and fibril formation and interrupts disease progression.
This study provides the basis for the study of the effect of tafamidis on the stability of transthyretin and its safety, tolerance and efficacy in patients with transthyretin amyloid polyneuropathy.
Read the detailed description
Transthyretin amyloidosis is a protein misfolding disease with a broad spectrum of manifestations. When the peripheral nerves are affected predominately, the disease is termed transthyretin amyloid polyneuropathy (ATTR-PN). When the heart is primarily affected, the disease is called transthyretin amyloid cardiomyopathy (ATTR-CM). ATTR-PN is a fatal illness resulting from autosomal dominantly inherited single-point mutations on the transthyretin gene.
Tafamidis is a specific stabilizer of both variant and wild-type TTR. Tafamidis binds to TTR at the thyroxine binding sites and inhibits TTR tetramer dissociation, the rate limiting step in the amyloidogenic process. The result disrupts the amyloid cascade and fibril formation and interrupts disease progression.
In China, ATTR-PN is rare, estimated at approximately 1997 persons . In recent years, about 30-40 case reports have been published and several ATTR-PN families were reported with different TTR gene mutations from those observed in Europe. Delay in the time to diagnosis is a major obstacle to the optimal management of ATTR-PN in China, and patients will typically wait several years between the emergence of first clinical signs and receiving an accurate diagnosis. There is a critical need to raise disease awareness, to facilitate earlier diagnosis and an urgency to enable access to treatment given the significant unmet medical need in this rare and fatal disease.
- Conditions
- Transthyretin Amyloidosis
- Being tested
- Tafamidis Pill
- Medical subject headings
- Amyloidosis, Hereditary, Transthyretin-Related
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tafamidis PillDrug
Oral
| Study group | Role | What they receive |
|---|---|---|
| Tafamidis group | Experimental | During the treatment period, each participant will receive 20 mg tafamidis meglumine once daily for 24 weeks. Receives: Drug: Tafamidis Pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
TTR stabilization compared with Baseline
TTR stabilization at Week 8 compared with Baseline, as measured by a validated immunoturbidimetric assay.
Measured: at Week 8
Secondary outcomes (9)
TTR stabilization
TTR stabilization at Week 8 compared with Baseline, as measured by a validated immunoturbidimetric assay.
Measured: each follow up visit after Week 8（Week 8, Week 12 and Week 24）
TTR concentration
Measured: at Day 1(baseline), Week 8, Week 12 and Week 24
Neuropathy Impairment Score：NIS-LL (lower limb)
Change from baseline
Measured: at Day 1(baseline) and Week 24
TQOL score and 5 domains as measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN)
Change from baseline
Measured: at Day 1(baseline) and Week 24
TQOL score and 5 domains asmeasured by the Norfolk
Change from baseline
Measured: at Day 1(baseline) and Week 24
"Σ7 NTs NDS" as measured by nerve conduction studies (NCS), vibration detection threshold (VDT) and heart rate response to deep breathing (HRDB).
Change from baseline
Measured: at Day 1(baseline) and Week 24
Modified Body Mass Index (mBMI).
Change from baseline
Measured: at Day 1(baseline) and Week 24
36-item survey form (SF-36).
Change from baseline
Measured: at Day 1(baseline) and Week 24
EQ-5D-5L Index Score.
Change from baseline
Measured: at Day 1(baseline) and Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2021
- Study start1 Jun 2021
- Primary completion1 Jun 2022 (estimated)
- Study completion1 Jun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transthyretin AmyloidosisStudies of the same condition, open and under way.
- More trials run by Peking University Third HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University Third Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04963985
- Sponsor's protocol ID
- M2020466
- Status last verified
- Jul 2021
- First submitted
- 27 Jun 2021
- Last updated
- 15 Jul 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Tafamidis on Transthyretin Stabilization, Safety, Tolerability and Efficacy in Transthyretin Amyloid Polyneuropathy Patients
- ClinicalTrials.gov ID
- NCT04963985
- Acronym / sponsor ID
- M2020466
- Conditions
- Transthyretin Amyloidosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Peking University Third HospitalUniversity, hospital or other
- Study start
- 1 Jun 2021 (actual)
- Primary completion
- 1 Jun 2022 (estimated)
- Study completion
- 1 Jun 2023 (estimated)
- First posted
- 15 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Transthyretin amyloid polyneuropathy (ATTR-PN) is a fatal illness resulting from autosomal dominantly inherited single-point mutations on the transthyretin gene.
Tafamidis is a specific stabilizer of both variant and wild-type TTR. Tafamidis binds to TTR at the thyroxine binding sites and inhibits TTR tetramer dissociation, the rate limiting step in the amyloidogenic process. The result disrupts the amyloid cascade and fibril formation and interrupts disease progression.
This study provides the basis for the study of the effect of tafamidis on the stability of transthyretin and its safety, tolerance and efficacy in patients with transthyretin amyloid polyneuropathy.
Detailed description
Transthyretin amyloidosis is a protein misfolding disease with a broad spectrum of manifestations. When the peripheral nerves are affected predominately, the disease is termed transthyretin amyloid polyneuropathy (ATTR-PN). When the heart is primarily affected, the disease is called transthyretin amyloid cardiomyopathy (ATTR-CM). ATTR-PN is a fatal illness resulting from autosomal dominantly inherited single-point mutations on the transthyretin gene.
Tafamidis is a specific stabilizer of both variant and wild-type TTR. Tafamidis binds to TTR at the thyroxine binding sites and inhibits TTR tetramer dissociation, the rate limiting step in the amyloidogenic process. The result disrupts the amyloid cascade and fibril formation and interrupts disease progression.
In China, ATTR-PN is rare, estimated at approximately 1997 persons . In recent years, about 30-40 case reports have been published and several ATTR-PN families were reported with different TTR gene mutations from those observed in Europe. Delay in the time to diagnosis is a major obstacle to the optimal management of ATTR-PN in China, and patients will typically wait several years between the emergence of first clinical signs and receiving an accurate diagnosis. There is a critical need to raise disease awareness, to facilitate earlier diagnosis and an urgency to enable access to treatment given the significant unmet medical need in this rare and fatal disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tafamidis group | Experimental | Drug: Tafamidis PillDuring the treatment period, each participant will receive 20 mg tafamidis meglumine once daily for 24 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- -
- Participants are eligible to be included in the study only if all of the following criteria apply:
- Male or female participants between the ages of 18 and 80 years.
- Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations and other study procedures.
- Participants have amyloid documented by biopsy in accordance with institutional site standard of care (Biopsy must have been performed within 5 years of enrollment).
Key exclusion criteria (20 listed)
- -
- Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
- Chronic use of non-protocol approved non-steroidal anti-inflammatory drugs (NSAIDs), defined as greater than 3-4 times/month. The following NSAID are allowed: acetylsalicylic acid, etodolac, ibuprofen, indomethacin, ketoprofen, nabumetone, naproxen, nimesulide, piroxicam, and sulindac.
- Use of diflunisal, tauroursodeoxycholate, doxycycline or a TTR stabilizing agent, or other experimental interventions for familial amyloidosis within 30 days prior to the study entry and/or during study participation. Participants who are taking or who have previously taken tafamidis.
- Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of investigational product used in this study (whichever is longer).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tafamidis PillOral | Drug | Tafamidis group |
Primary outcome
TTR stabilization compared with Baseline
Time frame: at Week 8
TTR stabilization at Week 8 compared with Baseline, as measured by a validated immunoturbidimetric assay.
9 secondary outcomes
TTR stabilization
Time frame: each follow up visit after Week 8（Week 8, Week 12 and Week 24）
TTR concentration
Time frame: at Day 1(baseline), Week 8, Week 12 and Week 24
Neuropathy Impairment Score：NIS-LL (lower limb)
Time frame: at Day 1(baseline) and Week 24
TQOL score and 5 domains as measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN)
Time frame: at Day 1(baseline) and Week 24
TQOL score and 5 domains asmeasured by the Norfolk
Time frame: at Day 1(baseline) and Week 24
"Σ7 NTs NDS" as measured by nerve conduction studies (NCS), vibration detection threshold (VDT) and heart rate response to deep breathing (HRDB).
Time frame: at Day 1(baseline) and Week 24
Modified Body Mass Index (mBMI).
Time frame: at Day 1(baseline) and Week 24
36-item survey form (SF-36).
Time frame: at Day 1(baseline) and Week 24
EQ-5D-5L Index Score.
Time frame: at Day 1(baseline) and Week 24
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2021.
- Individual participant dataSharing planned: No
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Active, not recruitingObservational study
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Active, not recruitingPhase 3
EPIC-ATTR: A Study to Evaluate the Effect of Eplontersen on the Transthyretin Reduction and Long-term Safety in Chinese Subjects With Transthyretin Amyloid Cardiomyopathy
Transthyretin Amyloid Cardiomyopathy
RecruitingObservational study
Essen Amyloidosis Registry
Amyloidosis; Systemic, Amyloidosis Cardiac
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A Phase 3 Study of NTLA-2001 in ATTRv-PN
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MAGNITUDE: A Phase 3 Study of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tafamidis Pill in people with Transthyretin Amyloidosis, run by Peking University Third Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TTR stabilization compared with Baseline (time frame: at Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2021.