Mycobacterium Infections, NontuberculousPhase 2IMPULSE-7NCT04154826
Recombinant Interleukin-7 (CYT107) to Treat Patients With Refractory Nontuberculous Mycobacterial Lung Disease
A Phase 2 study testing Recombinant human interleukin-7 in people with Mycobacterium Infections, Nontuberculous, run by Revimmune at 1 site in United States.
Trial summary
A prospective, single-center, single-blinded study involving patients with refractory nontuberculous mycobacteria lung disease to ascertain pharmacokinetics, safety, efficacy, and tolerability of two dose levels of parenteral administration of recombinant Interleukin-7 (IL-7) (CYT107). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Mycobacterium Infections, Nontuberculous
- What is being tested?
- Recombinant human interleukin-7
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Nov 2020to 30 Mar 2024
- Phase
- Phase 2
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females aged ≥18 years but <85 years who have given written informed consent to participate
- Diagnosis of pulmonary nontuberculous mycobacterial lung disease in accordance with the 2007 Infectious DiseasesSociety of America (IDSA) and AmericanThoracic Society (ATS) criteria with evidence of nodular bronchiectatic and/or cavitary disease by chest CT
- History of chronic, refractory infection with either Mycobacterium avium complex, defined as:
- Persistently positive mycobacterial sputum cultures after 6 or more months of guideline-based treatment (GBT), with at least one positive sputum culture within 2 months prior to the baseline visit and
- Currently on a stable guideline-based therapy that has been unchanged for the past 28 days. (GBT defined as a multi-drug regimen containing a macrolide and at least one other antimicrobial with activity against NTM.)
- Ability to produce at least 3 mL of sputum or be willing to undergo an induction to produce at least 3 mL of sputum for clinical evaluation
Show all 14Show fewer
- This study permits the re-enrollment of a participant who may have been discontinued as a pre-treatment screen failure prior to study drug treatment.
- Age and reproductive status:
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment
- Women must not be breastfeeding
- Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of treatment with CYT107 plus 5 half-lives of CYT107 (the terminal half-life of CYT107 is up to 2 days) plus 30 days (duration of ovulatory cycle) for a total of 2 months post-treatment completion.
- Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with CYT107 plus 5 half-lives of CYT107 plus 90 days (duration of sperm turnover) for a total of 7 months post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time.
- Azoospermic males are exempt from contraceptive requirements.
- WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements but still must undergo pregnancy testing as described in this section.
Who cannot join
- Cancer with current chemotherapy or radiotherapy (receipt of chemotherapy or radiotherapy for cancer within the last 6 months). All patients with current, or history of, hematologic malignancy (including, but not limited to, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), etc.) or lymphoma will be excluded, regardless of receipt of recent chemotherapy
- Active pulmonary tuberculosis requiring concomitant treatment at the time of screening
- Patients with history or current evidence of autoimmune disease including for example: myasthenia gravis, Guillain Barre syndrome, systemic lupus erythematosus, multiple sclerosis, scleroderma, ulcerative colitis, Crohn's disease, autoimmune hepatitis, Wegener's etc.
- Patients who have received solid organ transplant or bone marrow transplant
- Known history of infection with HIV or HIV positive test at screening
- Known history of chronic HBV (hepatitis B viral) infection and not on treatment with HBV nucleoside analogues prior to the current hospitalization or HBV DNA > 100 IU/mL
Show all 20Show fewer
- Known history of infection with HCV (hepatitis C virus) and currently undergoing treatment for HCV infections or has detectable HCV RNA
- History of splenectomy
- Any hematologic disease associated with hypersplenism, such as thalassemia, hereditary spherocytosis, Gaucher's Disease, and autoimmune hemolytic anemia
- Significant liver or renal dysfunction as evidence by at least 5 times greater than the upper limits of normal baseline ALT (alanine aminotransferase), AST (aspartate aminotransferase), alkaline phosphatase, or total bilirubin.
- Evidence of biliary cirrhosis with portal hypertension
- Participation in another investigational interventional study testing a drug or a medical device concurrently or within the last 28 days prior to study entry
- Patients receiving immunosuppressive drugs or concurrent immunotherapy or biologic agents; including: growth factors, cytokines and interleukins other than the study medication: Interleukin-2, Interferons α, β and γ, GM-CSF, G-CSF (colony stimulating factors), HIV vaccines, biologics including TNF alpha inhibitors (i.e. abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, ixekizumab, natalizumab, rituximab, secukinumab, tocilizumab, ustekinumab, vedolizumab, basiliximab and daclizumab), calcineurin inhibitors, mammalian target of rapamycin inhibitors, inosine monophosphate dehydrogenase inhibitors, Janus kinase inhibitors, hydroxyurea, immunoglobulins, adoptive cell therapy
- Patients receiving corticosteroids at a dose greater than 300mg hydrocortisone/ day or 25 mgs of prednisone per day or equivalent for more than 3 weeks
- Prior exposure to exogenous IL 7
- Inability to comply with the study treatment, study visits, and study procedures as assessed by the study PI or delegate
- Subjects with hemoptysis of ≥60 mL in a 24 hour period within 4 weeks prior to screening
- Addition of any new antimicrobial drug with known activity against Mycobacterium avium complex infection (i.e. amikacin, azithromycin, bedaquiline, clarithromycin, ciprofloxacin, clofazimine, ethambutol, eravacycline, levofloxacin, linezolid, moxifloxacin, omadacycline, rifampin, rifabutin, tedizolid, tigecycline tobramycin) within 28 days prior to Study Day 1
- Daily continuous oxygen supplementation >4 L/min
- Patients unlikely to survive a minimum of 30 days defined by (Systolic blood pressure) SBP<90 or hypoxia <80% SpO2 (oxygen saturation) -
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Recombinant Interleukin-7 (CYT107) to Treat Patients With Refractory Nontuberculous Mycobacterial Lung Disease. Two Doses Phase II, Single Center, Open-label Trial
A prospective, single-center, single-blinded study involving patients with refractory nontuberculous mycobacteria lung disease to ascertain pharmacokinetics, safety, efficacy, and tolerability of two dose levels of parenteral administration of recombinant Interleukin-7 (IL-7) (CYT107).
Read the detailed description
A single center, randomized, phase II, single blinded, two-dose level trial aimed at testing anti-mycobacterial activity of CYT107 in patients with non-tuberculous mycobacteria lung disease (NTMLD).
A total of 12 evaluable NTMLD patients from Washington University School of Medicine in St. Louis will be recruited and randomized 6:6 to study drug treatment at either 10μg/kg/wk or 20μg/kg/wk for two 4-week treatment periods.
The randomization will be stratified based on the presence of pulmonary cavitaries. A maximum of three patients with pulmonary cavitary disease will be allocated to each group.
A potential study extension is envisioned in the United Kingdom, in which case the protocol would be amended to increase the targeted enrollment and number of participating centers.
The aim of this trial is detection of an immuno-therapeutic response in patients with refractory NTMLD and to determine the potential rate of response and tolerance of CYT107 using two dose levels that indicated good immune response in other pathologies such as HIV, HCV, sepsis and various cancers.
For patients with refractory NTMLD, a control group is not beneficial as the standard of care treatment results are already known and documented.
All serious adverse events (SAEs) will be reported within 24 hours of notification
- Conditions
- Mycobacterium Infections, Nontuberculous
- Being tested
- Recombinant human interleukin-7
- Medical subject headings
- Mycobacterium Infections, Nontuberculous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant human interleukin-7Drug
Also called CYT107
weekly intra-muscular (IM) administration
| Study group | Role | What they receive |
|---|---|---|
| low dose | Experimental | CYT107 10µg/kg/week for 4 weeks (wk1-4) followed by no treatment during 4 weeks (wk 5-8) CYT107 10µg/kg/week for 4 weeks (wk9-12) Receives: Drug: Recombinant human interleukin-7 |
| high dose | Experimental | CYT107 20µg/kg/week for 4 weeks (wk1-4) followed by no treatment during 4 weeks (wk 5-8) CYT107 20µg/kg/week for 4 weeks (wk9-12) Receives: Drug: Recombinant human interleukin-7 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of the proportion of subjects with Acid Fast Bacilli (AFB) sputum culture conversion to negative at day 180.
Percentage of participants with 3 consecutive monthly, negative Acid Fast Bacilli sputum cultures at any time within first 6 months
Measured: six months
Secondary outcomes (12)
Efficacy by kinetic of AFB sputum culture conversion to negative.
number of patients with negative sputum conversion measured at days 28, 56, 84, 112, 140, 180, 240, 300, and 360.
Measured: one year
Improvement of functional capacity response assessed by the median change in the 6-minute walk distance compared to baseline.
Increase in 6-minute walking distance measured at days 84, 180 and 360 over baseline distance
Measured: one year
Improvement of functional capacity response assessed by the median change in oxygen saturation compared to baseline.
Increase in oxygen saturation measured at days 84, 180 and 360 over baseline value
Measured: one year
Pulmonary function response measured by the median improvement in the Forced expiratory volume during the first second (FEV1).
ratio of Forced Expiratory Volume during the first second (FEV1) measured at days 180 and 360 over the same measure at baseline.
Measured: one year
Radiological response on chest CT compared to baseline
Surface area of lung involved by clinical chest computerized tomography (CT) scans at days 180 and 360 compared to baseline
Measured: one year
Improvement of Health-related Quality of Life (HRQoL)
Patient-Reported Outcomes Measurement Information System (PROMIS-29 ) measured at days 56, 84, 180, 300 and 360 and compared to baseline.
(The mean healthy population score is 50. The score increases with worsening medical condition.)
Measured: one year
Number of hospital readmissions
Cumulated Number of hospital (Intensive care unit or emergency room ) visits at days 56, 84, 180, 300 and 360
Measured: one year
C max (maximal plasma concentration) pharmacokinetic of CYT107 in this population
At Day 1 and Day 78 measure of CYT107 Cmax
Measured: One day
Plasma concentration area under curve (AUC) pharmacokinetic of CYT107 in this population
At Day 1 and Day 78 measure of CYT107 AUC
Measured: One day
Clinical tolerance of CYT107 indicated by the study drop-out rate (%) regardless of the cause.
Percentage of patients who dropout of the study at days 28, 84, 180
Measured: six months
Proportion of patients developing any grade 3-4 adverse events or deaths
Percentage of patients with grade 3-4 adverse events (assessed by CTCAE version 5.0) or deaths through day 360.
Measured: one year
Measure of CYT107 immunogenicity
Number of patients with presence of binding and neutralizing antibodies at day 15, 29, 57, 90 and 120 compared to baseline. Testing for immunogenicity will be repeated at day 180 and again at day 360 only if positive antibodies are detected at previous sampling timepoint.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2019
- Study start30 Nov 2020
- Primary completion31 Dec 2023
- Study completion30 Mar 2024
Why it stopped: non convincing results
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mycobacterium Infections, NontuberculousStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two dose level parallel groups
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Revimmune
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Washington University School of Medicine
- Responsible party
- Sponsor
- Investigators
- Andrej SPEC, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04154826
- Sponsor's protocol ID
- IMPULSE-7
- Acronym
- IMPULSE-7
- Status last verified
- Apr 2024
- First submitted
- 28 Oct 2019
- Last updated
- 11 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mejia-Chew C, Spec A, Walton AH, Ulezko Antonova A, Dram A, Bhalla S, Colonna M, Morre M, Hotchkiss R. Recombinant interleukin-7 treatment of refractory Mycobacterium avium complex lung disease (IMPULSE-7): a pilot phase II, single-center, randomized, clinical trial. Ther Adv Infect Dis. 2025 May 10;12:20499361251339300. doi: 10.1177/20499361251339300. eCollection 2025 Jan-Dec.
PubMed 40351870
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Recombinant Interleukin-7 (CYT107) to Treat Patients With Refractory Nontuberculous Mycobacterial Lung Disease. Two Doses Phase II, Single Center, Open-label Trial
- ClinicalTrials.gov ID
- NCT04154826
- Acronym / sponsor ID
- IMPULSE-7 / IMPULSE-7
- Conditions
- Mycobacterium Infections, Nontuberculous
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: non convincing results
- Enrolment
- 8 participants (actual)
- Lead sponsor
- RevimmuneIndustry (pharma, biotech, devices)
- Collaborators
- Washington University School of Medicine
- Study start
- 30 Nov 2020 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 30 Mar 2024 (actual)
- First posted
- 7 Nov 2019 (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.
A prospective, single-center, single-blinded study involving patients with refractory nontuberculous mycobacteria lung disease to ascertain pharmacokinetics, safety, efficacy, and tolerability of two dose levels of parenteral administration of recombinant Interleukin-7 (IL-7) (CYT107).
Detailed description
A single center, randomized, phase II, single blinded, two-dose level trial aimed at testing anti-mycobacterial activity of CYT107 in patients with non-tuberculous mycobacteria lung disease (NTMLD).
A total of 12 evaluable NTMLD patients from Washington University School of Medicine in St. Louis will be recruited and randomized 6:6 to study drug treatment at either 10μg/kg/wk or 20μg/kg/wk for two 4-week treatment periods.
The randomization will be stratified based on the presence of pulmonary cavitaries. A maximum of three patients with pulmonary cavitary disease will be allocated to each group.
A potential study extension is envisioned in the United Kingdom, in which case the protocol would be amended to increase the targeted enrollment and number of participating centers.
The aim of this trial is detection of an immuno-therapeutic response in patients with refractory NTMLD and to determine the potential rate of response and tolerance of CYT107 using two dose levels that indicated good immune response in other pathologies such as HIV, HCV, sepsis and various cancers.
For patients with refractory NTMLD, a control group is not beneficial as the standard of care treatment results are already known and documented.
All serious adverse events (SAEs) will be reported within 24 hours of notification
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Two dose level parallel groups
| Arm | Type | Receives |
|---|---|---|
| low dose | Experimental | Drug: Recombinant human interleukin-7CYT107 10µg/kg/week for 4 weeks (wk1-4) followed by no treatment during 4 weeks (wk 5-8) CYT107 10µg/kg/week for 4 weeks (wk9-12) |
| high dose | Experimental | Drug: Recombinant human interleukin-7CYT107 20µg/kg/week for 4 weeks (wk1-4) followed by no treatment during 4 weeks (wk 5-8) CYT107 20µg/kg/week for 4 weeks (wk9-12) |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Males and females aged ≥18 years but <85 years who have given written informed consent to participate
- Diagnosis of pulmonary nontuberculous mycobacterial lung disease in accordance with the 2007 Infectious DiseasesSociety of America (IDSA) and AmericanThoracic Society (ATS) criteria with evidence of nodular bronchiectatic and/or cavitary disease by chest CT
- History of chronic, refractory infection with either Mycobacterium avium complex, defined as:
- Ability to produce at least 3 mL of sputum or be willing to undergo an induction to produce at least 3 mL of sputum for clinical evaluation
- This study permits the re-enrollment of a participant who may have been discontinued as a pre-treatment screen failure prior to study drug treatment.
Key exclusion criteria (20 listed)
- Cancer with current chemotherapy or radiotherapy (receipt of chemotherapy or radiotherapy for cancer within the last 6 months). All patients with current, or history of, hematologic malignancy (including, but not limited to, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), etc.) or lymphoma will be excluded, regardless of receipt of recent chemotherapy
- Active pulmonary tuberculosis requiring concomitant treatment at the time of screening
- Patients with history or current evidence of autoimmune disease including for example: myasthenia gravis, Guillain Barre syndrome, systemic lupus erythematosus, multiple sclerosis, scleroderma, ulcerative colitis, Crohn's disease, autoimmune hepatitis, Wegener's etc.
- Patients who have received solid organ transplant or bone marrow transplant
- Known history of infection with HIV or HIV positive test at screening
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 |
|---|---|---|
| Recombinant human interleukin-7Also: CYT107weekly intra-muscular (IM) administration | Drug | high dose, low dose |
Primary outcome
Determination of the proportion of subjects with Acid Fast Bacilli (AFB) sputum culture conversion to negative at day 180.
Time frame: six months
Percentage of participants with 3 consecutive monthly, negative Acid Fast Bacilli sputum cultures at any time within first 6 months
12 secondary outcomes
Efficacy by kinetic of AFB sputum culture conversion to negative.
Time frame: one year
Improvement of functional capacity response assessed by the median change in the 6-minute walk distance compared to baseline.
Time frame: one year
Improvement of functional capacity response assessed by the median change in oxygen saturation compared to baseline.
Time frame: one year
Pulmonary function response measured by the median improvement in the Forced expiratory volume during the first second (FEV1).
Time frame: one year
Radiological response on chest CT compared to baseline
Time frame: one year
Improvement of Health-related Quality of Life (HRQoL)
Time frame: one year
Number of hospital readmissions
Time frame: one year
C max (maximal plasma concentration) pharmacokinetic of CYT107 in this population
Time frame: One day
Plasma concentration area under curve (AUC) pharmacokinetic of CYT107 in this population
Time frame: One day
Clinical tolerance of CYT107 indicated by the study drop-out rate (%) regardless of the cause.
Time frame: six months
Proportion of patients developing any grade 3-4 adverse events or deaths
Time frame: one year
Measure of CYT107 immunogenicity
Time frame: 1 year
Results and safety
The study was stopped early (reason given: non convincing results). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2024.
- Derived from this study: PubMed 40351870Mejia-Chew C, Spec A, Walton AH, Ulezko Antonova A, Dram A, Bhalla S, Colonna M, Morre M, Hotchkiss R. Recombinant interleukin-7 treatment of refractory Mycobacterium avium complex lung disease (IMPULSE-7): a pilot phase II, single-center, randomized, clinical trial. Ther Adv Infect Dis. 2025 May 10;12:20499361251339300. doi: 10.1177/20499361251339300. eCollection 2025 Jan-Dec.
- Individual participant dataSharing planned: No
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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.
Andrej SPEC, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Recombinant human interleukin-7 in people with Mycobacterium Infections, Nontuberculous, run by Revimmune at 1 site in United States.
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 14 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: stopped early, as of the sponsor's last update on 11 Apr 2024. 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 United States. 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?
The study was stopped early (reason given: non convincing results). Results are not available in the source record.
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?
Determination of the proportion of subjects with Acid Fast Bacilli (AFB) sputum culture conversion to negative at day 180. (time frame: six months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04154826, which also lists 1 linked publication.
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 11 Apr 2024.