Recombinant Interleukin-7 (CYT107) to Treat Patients With Refractory Nontuberculous Mycobacterial Lung Disease

NCT04154826 | Terminated Phase 2 FDA Drug

• 1 other identifier: IMPULSE-7
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Mycobacterium Infections, Nontuberculous

Outcome Measures

Primary Outcomes (1)

• 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

  six months

Secondary Outcomes (12)

• Efficacy by kinetic of AFB sputum culture conversion to negative.

  one year

• Improvement of functional capacity response assessed by the median change in the 6-minute walk distance compared to baseline.

  one year

• Improvement of functional capacity response assessed by the median change in oxygen saturation compared to baseline.

  one year

• Pulmonary function response measured by the median improvement in the Forced expiratory volume during the first second (FEV1).

  one year

• Radiological response on chest CT compared to baseline

  one year

Other Outcomes (6)

• IL-7 effect on opportunistic bacterial, viral or fungal infections

  one year

• IL-7 Effects on immune cells counts

  one year

• IL-7 Effects on CD4+ and CD8+ T lymphocytes

  one year

Study Arms (2)

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)

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)

Drug: Recombinant human interleukin-7

Interventions

Recombinant human interleukin-7 DRUG

weekly intra-muscular (IM) administration

Also known as: CYT107

high dose; low dose

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Revimmune: lead
• Washington University School of Medicine: collaborator

Study Sites (1)

Washington University

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• 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.

  PMID: 40351870 DERIVED

MeSH Terms

Conditions

Mycobacterium Infections, Nontuberculous

Interventions

Interleukin-7

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Andrej SPEC, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two dose level parallel groups

Study Record Dates

• First Submitted: October 28, 2019
• First Posted: November 7, 2019
• Study Start: November 30, 2020
• Primary Completion: December 31, 2023
• Study Completion: March 30, 2024
• Last Updated: April 11, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)