Familial Cold Autoinflammatory SyndromePhase 2DFV890-FCASNCT04868968
Study of Safety, Tolerability and Efficacy of DFV890 in Participants With Familial Cold Auto-inflammatory Syndrome (FCAS)
A Phase 2 study testing DFV890 in people with Familial Cold Autoinflammatory Syndrome, run by Novartis Pharmaceuticals at 3 sites in 3 countries.
Trial summary
The purpose of this phase II study was to assess the safety, tolerability and efficacy of DFV890 in participants with FCAS. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Familial Cold Autoinflammatory Syndrome
- What is being tested?
- DFV890
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 20 Sep 2021to 5 May 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Written informed consent must be obtained before any study-specific assessment is performed
- Body mass index within the range of 18-35 kg/m2
- Patients with a genetic diagnosis of FCAS
- Patients with a clinical history and investigations consistent with FCAS
Who cannot join
- Anti-rejection and/or immunomodulatory drugs must be discontinued (please, see protocol for further details)
- Clinically significant, suspected active or chronic bacterial (including Mycobacterium tuberculosis), viral or fungal infection within 30 days prior to Day 1.
- Patients with innate (e.g. TLR immunodeficiencies, defects in IFN-γ signaling) or acquired immune deficiencies (e.g. AIDS).
- Presence of human immunodeficiency virus (HIV) infection, hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (anti-HBc), or hepatitis C antibodies at screening.
- Live vaccines within 4 weeks of Day 1
- Pregnant or nursing (lactating) women.
- Women of child-bearing potential unless they are using highly effective methods of contraception.
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
United States1 site
Novartis Investigative Site
La Jolla, California, 92093
About this study
Official title: An Open-label, Single Arm Phase II Study of DFV890 to Assess the Safety, Tolerability and Efficacy in Participants With Familial Cold Auto-inflammatory Syndrome (FCAS)
The purpose of this phase II study was to assess the safety, tolerability and efficacy of DFV890 in participants with FCAS.
Read the detailed description
This was an open-label, single-arm, multiple dose, phase II study to assess safety, tolerability and clinical efficacy of DFV890 in participants with FCAS who showed evidence of inflammatory activity after the cold challenge performed during screening.
The study included a screening period, a treatment period and a follow-up period.
- Conditions
- Familial Cold Autoinflammatory Syndrome
- Being tested
- DFV890
- Keywords
- Familial Cold Auto-inflammatory Syndrome, FCAS, DFV890, NLRP3 inhibitor, inflammasome inhibition, Cryopyrin-associated periodic syndromes, CAPS
- Medical subject headings
- Cryopyrin-Associated Periodic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DFV890Drug
100 mg of DFV890 film coated tablets twice daily (b.i.d.). for 3 days starting in the morning of Day 1 and 100 mg of DFV890 in the morning on the fourth day.
| Study group | Role | What they receive |
|---|---|---|
| DFV890 | Experimental | DFV890 Receives: Drug: DFV890 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ratio of Fold Change From Pre-challenge to the Highest Post-challenge Value of White Cell Count (WCC) Between Treatment and Screening Period
A cold challenge was performed during the screening period and on Day 4 of the treatment period. Fold change from pre-challenge to highest post-challenge value of WCC was defined as the ratio of the highest post-challenge WCC value to the pre-challenge WCC value. The ratio of fold change was defined as treatment fold change divided by the screen fold change. A value of less than 1 for the ratio of fold change indicates a lower relative increase of WCC in the treatment than in the screening period, which is a favorable outcome. The log-transformed fold change from pre-challenge to the highest post challenge WCC was analyzed using a log-linear mixed effect model. The analysis was carried out considering the data from -2 to 8 hrs post challenge. The unforeseen screen failure rate and recruitment challenges resulted in early closure of the study. Only 4 out of planned 6 participants were enrolled in the study; thus, the results should be interpreted cautiously.
Measured: Screening period and treatment period (Day 4): pre cold challenge and up to 8 hours post cold challenge. The duration of the cold challenge was 45 minutes.
Secondary outcomes (4)
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of participants with treatment emergent AEs (any AE regardless of seriousness), AEs led to study treatment discontinuation, SAEs and SAEs led to study treatment discontinuation.
Measured: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 34 days
Physician Global Assessment of Autoinflammatory Disease Activity
The Physician global assessment of autoinflammatory disease activity is a questionnaire completed by the Investigator. It uses a 5-point scale. Lower scores represent better outcomes.
0 = Absent
- = Minimal
- = Mild
- = Moderate
- = Severe
Measured: Screening and Treatment (Day 4): 1 hour pre and 2, 3, 5, 9 and 24 hours post. Scheduled time refers to the time post-meal (screening) and to the time post-dose (treatment). The start of the cold challenge is at 1 hour post and the duration is 45 minutes.
Physician's Severity Assessment of Autoinflammatory Disease Signs and Symptoms
The Physician's severity assessment of autoinflammatory disease signs and symptoms is a questionnaire completed by the Investigator. It uses a 5-point scale. Lower scores represent better outcomes.
0 = Absent
- = Minimal
- = Mild
- = Moderate
- = Severe
The following items were assessed:
- Assessment of skin disease (urticarial skin rash)
- Assessment of arthralgia
- Assessment of myalgia
- Assessment of headache/migraine
- Assessment of conjunctivitis
- Assessment of fatigue/malaise
Measured: Screening and Treatment (Day 4): 1 hour pre and 2, 3, 5, 9 and 24 hours post. Scheduled time refers to the time post-meal (screening) and to the time post-dose (treatment). The start of the cold challenge is at 1 hour post and the duration is 45 minutes.
Patient's Global Assessment of Disease Activity
Patient's global assessment of disease activity is a questionnaire completed by the patient. It uses a 5-point scale. The patient selected a rating based on the patient's current disease activity at the time of the assessment. Lower scores represent better outcomes.
0 = Absent
- = Minimal
- = Mild
- = Moderate
- = Severe
Measured: Screening and Treatment (Day 4): 1 hour pre and 2, 3, 5, 9 and 24 hours post. Scheduled time refers to the time post-meal (screening) and to the time post-dose (treatment). The start of the cold challenge is at 1 hour post and the duration is 45 minutes.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2021
- Study start20 Sep 2021
- Primary completion13 Dec 2022
- Study completion5 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Familial Cold Autoinflammatory SyndromeStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04868968
- Sponsor's protocol ID
- CDFV890A12201
- Other IDs
- 2020-005948-33
- Acronym
- DFV890-FCAS
- Status last verified
- Oct 2024
- First submitted
- 22 Apr 2021
- Last updated
- 9 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single Arm Phase II Study of DFV890 to Assess the Safety, Tolerability and Efficacy in Participants With Familial Cold Auto-inflammatory Syndrome (FCAS)
- ClinicalTrials.gov ID
- NCT04868968
- Acronym / sponsor ID
- DFV890-FCAS / CDFV890A12201
- Conditions
- Familial Cold Autoinflammatory Syndrome
- Keywords
- Familial Cold Auto-inflammatory Syndrome, FCAS, DFV890, NLRP3 inhibitor, inflammasome inhibition, Cryopyrin-associated periodic syndromes, CAPS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 20 Sep 2021 (actual)
- Primary completion
- 13 Dec 2022 (actual)
- Study completion
- 5 May 2023 (actual)
- First posted
- 3 May 2021 (actual)
- Results
- Posted 3 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this phase II study was to assess the safety, tolerability and efficacy of DFV890 in participants with FCAS.
Detailed description
This was an open-label, single-arm, multiple dose, phase II study to assess safety, tolerability and clinical efficacy of DFV890 in participants with FCAS who showed evidence of inflammatory activity after the cold challenge performed during screening.
The study included a screening period, a treatment period and a follow-up period.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DFV890 | Experimental | Drug: DFV890DFV890 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Written informed consent must be obtained before any study-specific assessment is performed
- Body mass index within the range of 18-35 kg/m2
- Patients with a genetic diagnosis of FCAS
- Patients with a clinical history and investigations consistent with FCAS
Key exclusion criteria (8 listed)
- Anti-rejection and/or immunomodulatory drugs must be discontinued (please, see protocol for further details)
- Clinically significant, suspected active or chronic bacterial (including Mycobacterium tuberculosis), viral or fungal infection within 30 days prior to Day 1.
- Patients with innate (e.g. TLR immunodeficiencies, defects in IFN-γ signaling) or acquired immune deficiencies (e.g. AIDS).
- Presence of human immunodeficiency virus (HIV) infection, hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (anti-HBc), or hepatitis C antibodies at screening.
- Live vaccines within 4 weeks of Day 1
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 |
|---|---|---|
| DFV890100 mg of DFV890 film coated tablets twice daily (b.i.d.). for 3 days starting in the morning of Day 1 and 100 mg of DFV890 in the morning on the fourth day. | Drug | DFV890 |
Primary outcome
Ratio of Fold Change From Pre-challenge to the Highest Post-challenge Value of White Cell Count (WCC) Between Treatment and Screening Period
Time frame: Screening period and treatment period (Day 4): pre cold challenge and up to 8 hours post cold challenge. The duration of the cold challenge was 45 minutes.
A cold challenge was performed during the screening period and on Day 4 of the treatment period. Fold change from pre-challenge to highest post-challenge value of WCC was defined as the ratio of the highest post-challenge WCC value to the pre-challenge WCC value. The ratio of fold change was defined as treatment fold change divided by the screen fold change. A value of less than 1 for the ratio of fold change indicates a lower relative increase of WCC in the treatment than in the screening period, which is a favorable outcome. The log-transformed fold change from pre-challenge to the highest post challenge WCC was analyzed using a log-linear mixed effect model. The analysis was carried out considering the data from -2 to 8 hrs post challenge. The unforeseen screen failure rate and recruitment challenges resulted in early closure of the study. Only 4 out of planned 6 participants were enrolled in the study; thus, the results should be interpreted cautiously.
4 secondary outcomes
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 34 days
Physician Global Assessment of Autoinflammatory Disease Activity
Time frame: Screening and Treatment (Day 4): 1 hour pre and 2, 3, 5, 9 and 24 hours post. Scheduled time refers to the time post-meal (screening) and to the time post-dose (treatment). The start of the cold challenge is at 1 hour post and the duration is 45 minutes.
Physician's Severity Assessment of Autoinflammatory Disease Signs and Symptoms
Time frame: Screening and Treatment (Day 4): 1 hour pre and 2, 3, 5, 9 and 24 hours post. Scheduled time refers to the time post-meal (screening) and to the time post-dose (treatment). The start of the cold challenge is at 1 hour post and the duration is 45 minutes.
Patient's Global Assessment of Disease Activity
Time frame: Screening and Treatment (Day 4): 1 hour pre and 2, 3, 5, 9 and 24 hours post. Scheduled time refers to the time post-meal (screening) and to the time post-dose (treatment). The start of the cold challenge is at 1 hour post and the duration is 45 minutes.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing DFV890 in people with Familial Cold Autoinflammatory Syndrome, run by Novartis Pharmaceuticals at 3 sites in 3 countries.
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 4 inclusion and 8 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: finished, as of the sponsor's last update on 9 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, France, Germany. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ratio of Fold Change From Pre-challenge to the Highest Post-challenge Value of White Cell Count (WCC) Between Treatment and Screening Period (time frame: Screening period and treatment period (Day 4): pre cold challenge and up to 8 hours post cold challenge. The duration of the cold challenge was 45 minutes.). 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 9 Oct 2024.