Diabetes MellitusPhase 2NCT02691247
Safety and Efficacy of CLBS03 in Adolescents With Recent Onset Type 1 Diabetes (The Sanford Project T-Rex Study)
A Phase 2 study testing CLBS03 Low Dose and CLBS03 High Dose in people with Diabetes Mellitus, run by Lisata Therapeutics, Inc. at 15 sites in United States.
Trial summary
This clinical trial will explore the safety and effect of autologous ex vivo expanded polyclonal regulatory T-cells on beta cell function in patients, aged 8 to 17, with recent onset T1DM. Other measures of diabetes severity and the autoimmune response underlying T1DM will also be explored. Read more about this study
- Who is it for?
- Ages 8 to 17 years
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- CLBS03 Low Dose and CLBS03 High Dose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 113 participants
- Where
- 15 sitesUnited States
- Study dates
- Feb 2016to Jan 2020
- 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 8 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male and females aged 8 to 17 years of age
- Diagnosis of T1DM within 100 days of receipt of study drug
- Positive for at least one islet cell autoantibody
- Peak MMTT-stimulated C-peptide level > 0.2 pmol/mL (at the screening visit)
- Weight of ≥30 kg
- Must agree to use a reliable and acceptable method of contraception for the duration of participation
- Willing and medically acceptable to postpone live vaccine immunizations for one year after infusion
- Written informed consent and written assent
Who cannot join
- Hemoglobin less than the lower limit of normal
- Leukocytes <3,000/μL; neutrophils <1,500/μL; lymphocytes <800/μL; platelets <100,000/μL
- Regulatory T-cells present in peripheral blood at <20 cells per μL
- Current or ongoing use of non-insulin pharmaceuticals (that may affect glycemic control)
- Current or anticipated use of systemic corticosteroids or other immunomodulatory drugs
- Recent serious bacterial, viral, fungal, or other opportunistic infections
Show all 17Show fewer
- History of malignancy or serious uncontrolled cardiovascular, nervous system, pulmonary, renal, or gastrointestinal disease
- Serologic evidence of current or past viral infection: human immunodeficiency virus (HIV), Hepatitis B, Hepatitis C, and human T-lymphotropic virus (HTLV) 1/2
- Positive QuantiFERON® tuberculosis (TB) test, purified protein derivative (PPD) skin test, history of tuberculosis, or active TB infection
- Active infection with Epstein-Barr Virus or Cytomegalovirus
- Liver disease
- Pregnant or breast-feeding
- Vaccination with a live virus within 8 weeks of receipt of study drug
- Vaccination with a killed virus within 2 weeks of receipt of study drug
- Participation in an investigational drug study within 90 days prior to screening
- Previously treated with a T-Reg based cell therapy
- History of allergy to gentamicin
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Barbara Davis Center for Diabetes
Aurora, Colorado, 80045
Joslin Diabetes Center
Boston, Massachusetts, 02215
Sanford Research
Fargo, North Dakota, 58122
University of Florida
Gainesville, Florida, 32610
Baylor College of Medicine / Texas Children's Hospital
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
Children's Mercy Kansas City
Kansas City, Missouri, 64108
University of Miami, Diabetes Research Institute
Miami, Florida, 33136
University of Minnesota
Minneapolis, Minnesota, 55455
Vanderbilt Eskind Diabetes Clinic
Nashville, Tennessee, 37232
Yale University School of Medicine
New Haven, Connecticut, 06519
Oregon Health Science University
Portland, Oregon, 97239
Rady Children's Hospital
San Diego, California, 92123
University of California, San Francisco
San Francisco, California, 94143
Sanford Research
Sioux Falls, South Dakota, 57104
About this study
Official title: A Prospective Randomized Placebo-Controlled Double Blind Clinical Trial to Evaluate the Safety and Efficacy of CLBS03 (Autologous Ex Vivo Expanded Polyclonal Regulatory T-cells) in Adolescents With Recent Onset Type 1 Diabetes Mellitus (T1DM)
This clinical trial will explore the safety and effect of autologous ex vivo expanded polyclonal regulatory T-cells on beta cell function in patients, aged 8 to 17, with recent onset T1DM. Other measures of diabetes severity and the autoimmune response underlying T1DM will also be explored. Eligible subjects will receive a single infusion of CLBS03 (high or low dose) or placebo.
- Conditions
- Diabetes Mellitus
- Being tested
- CLBS03 Low Dose, CLBS03 High Dose, Placebo
- Keywords
- T1DM, Type 1 Diabetes Mellitus, T regulatory cell, Immunotherapy, Cell therapy, T-Reg
- Medical subject headings
- Diabetes Mellitus, Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CLBS03 Low DoseBiological
CLBS03 High DoseBiological
PlaceboBiological
| Study group | Role | What they receive |
|---|---|---|
| CLBS03 Low Dose | Experimental | A single infusion of CLBS03 Low Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP (United States Pharmacopoeia) infusion solution. Receives: Biological: CLBS03 Low Dose |
| CLBS03 High Dose | Experimental | A single infusion of CLBS03 High Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP infusion solution. Receives: Biological: CLBS03 High Dose |
| Placebo | Placebo comparator | A single infusion of placebo, consisting of the infusion solution only Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 52
The area-under-curve of sequential C-peptide concentrations (AUC-Cpep) during the mixed-meal tolerance test (MMTT) is the gold-standard method to assess residual beta-cell (ie, insulin) secretion in type 1 diabetes.
Measured: Week 52
Secondary outcomes (3)
Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 104
The area-under-curve of sequential C-peptide concentrations (AUC-Cpep) during the mixed-meal tolerance test (MMTT) is the gold-standard method to assess residual beta-cell (ie, insulin) secretion in type 1 diabetes.
Measured: Week 104
Change in Hemoglobin A1c (HbA1c)
Measured: Week 104
Change From Baseline in Mean Daily Dose of Insulin
Measured: Week 104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2016 (estimated)
- Study startFeb 2016
- Primary completionMar 2019
- Study completionJan 2020
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies 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
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 113 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lisata Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Sanford Health, California Institute for Regenerative Medicine (CIRM)
- Responsible party
- Sponsor
- Investigators
- Douglas Losordo, MD, Study director, Caladrius Biosciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02691247
- Sponsor's protocol ID
- CLBS03-P01
- Status last verified
- Dec 2020
- First submitted
- 12 Feb 2016
- Last updated
- 8 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Bender C, Wiedeman AE, Hu A, Ylescupidez A, Sietsema WK, Herold KC, Griffin KJ, Gitelman SE, Long SA; T-Rex Study Groupdagger; T-Rex Clinical Study Group. A phase 2 randomized trial with autologous polyclonal expanded regulatory T cells in children with new-onset type 1 diabetes. Sci Transl Med. 2024 May 8;16(746):eadn2404. doi: 10.1126/scitranslmed.adn2404. Epub 2024 May 8.
PubMed 38718135
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Randomized Placebo-Controlled Double Blind Clinical Trial to Evaluate the Safety and Efficacy of CLBS03 (Autologous Ex Vivo Expanded Polyclonal Regulatory T-cells) in Adolescents With Recent Onset Type 1 Diabetes Mellitus (T1DM)
- ClinicalTrials.gov ID
- NCT02691247
- Acronym / sponsor ID
- CLBS03-P01
- Conditions
- Diabetes Mellitus
- Keywords
- T1DM, Type 1 Diabetes Mellitus, T regulatory cell, Immunotherapy, Cell therapy, T-Reg
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 113 participants (actual)
- Lead sponsor
- Lisata Therapeutics, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Sanford Health, California Institute for Regenerative Medicine (CIRM)
- Study start
- Feb 2016 (actual)
- Primary completion
- Mar 2019 (actual)
- Study completion
- Jan 2020 (actual)
- First posted
- 25 Feb 2016 (estimated)
- Results
- Posted 8 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial will explore the safety and effect of autologous ex vivo expanded polyclonal regulatory T-cells on beta cell function in patients, aged 8 to 17, with recent onset T1DM. Other measures of diabetes severity and the autoimmune response underlying T1DM will also be explored. Eligible subjects will receive a single infusion of CLBS03 (high or low dose) or placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| CLBS03 Low Dose | Experimental | Biological: CLBS03 Low DoseA single infusion of CLBS03 Low Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP (United States Pharmacopoeia) infusion solution. |
| CLBS03 High Dose | Experimental | Biological: CLBS03 High DoseA single infusion of CLBS03 High Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP infusion solution. |
| Placebo | Placebo comparator | Biological: PlaceboA single infusion of placebo, consisting of the infusion solution only |
Who may qualify
- Ages
- 8 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Male and females aged 8 to 17 years of age
- Diagnosis of T1DM within 100 days of receipt of study drug
- Positive for at least one islet cell autoantibody
- Peak MMTT-stimulated C-peptide level > 0.2 pmol/mL (at the screening visit)
- Weight of ≥30 kg
Key exclusion criteria (17 listed)
- Hemoglobin less than the lower limit of normal
- Leukocytes <3,000/μL; neutrophils <1,500/μL; lymphocytes <800/μL; platelets <100,000/μL
- Regulatory T-cells present in peripheral blood at <20 cells per μL
- Current or ongoing use of non-insulin pharmaceuticals (that may affect glycemic control)
- Current or anticipated use of systemic corticosteroids or other immunomodulatory drugs
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 |
|---|---|---|
| CLBS03 Low Dose | Biological | CLBS03 Low Dose |
| CLBS03 High Dose | Biological | CLBS03 High Dose |
| Placebo | Biological | Placebo |
Primary outcome
Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 52
Time frame: Week 52
The area-under-curve of sequential C-peptide concentrations (AUC-Cpep) during the mixed-meal tolerance test (MMTT) is the gold-standard method to assess residual beta-cell (ie, insulin) secretion in type 1 diabetes.
3 secondary outcomes
Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 104
Time frame: Week 104
Change in Hemoglobin A1c (HbA1c)
Time frame: Week 104
Change From Baseline in Mean Daily Dose of Insulin
Time frame: Week 104
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38718135Bender C, Wiedeman AE, Hu A, Ylescupidez A, Sietsema WK, Herold KC, Griffin KJ, Gitelman SE, Long SA; T-Rex Study Groupdagger; T-Rex Clinical Study Group. A phase 2 randomized trial with autologous polyclonal expanded regulatory T cells in children with new-onset type 1 diabetes. Sci Transl Med. 2024 May 8;16(746):eadn2404. doi: 10.1126/scitranslmed.adn2404. Epub 2024 May 8.
- 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.
Douglas Losordo, MD study director
Caladrius Biosciences
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CLBS03 Low Dose and CLBS03 High Dose in people with Diabetes Mellitus, run by Lisata Therapeutics, Inc. at 15 sites 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 8 inclusion and 17 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 8 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites 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. Some participants in this study may receive a placebo. 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 8 Jan 2021). 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?
Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 52 (time frame: Week 52). 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 NCT02691247, 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 8 Jan 2021.