Celiac DiseasePhase 2NCT00362856
Safety and Tolerability Study of Larazotide Acetate in Celiac Disease Subjects
A Phase 2 study testing larazotide acetate in people with Celiac Disease, run by 9 Meters Biopharma, Inc. at 9 sites in United States.
Trial summary
This study was run to determine the safety, tolerance, and efficacy of multiple doses of larazotide acetate in subjects with celiac disease following a gluten challenge. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Celiac Disease
- What is being tested?
- larazotide acetate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 9 sitesUnited States
- Study dates
- 13 Sep 2006to 6 Mar 2007
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must have been diagnosed with celiac disease by biopsy for ≥ 6 months.
- Have a Anti-Tissue Transglutaminase (tTG) ≤ 10 EU as measured by serology.
- Must be on a gluten-free diet for at least the past 6 months.
Who cannot join
- Have any chronic active GI disease other than celiac disease (e.g., IBS, Crohn's, Colitis).
- Have diabetes (Type 1 or Type 2).
- Chronically consumes non-steroidal anti-inflammatory agents ("NSAIDs") or takes proton-pump inhibitors.
- Consuming oral corticosteroids or immune suppressants.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Study site
Bismarck, North Dakota, 58501
Research Site
Boston, Massachusetts, 02215
Study site
Morristown, New Jersey, 07960
Research Site
Philadelphia, Pennsylvania, 19107
Study site
Pittsburgh, Pennsylvania, 15241
Research Site
Richmond, Virginia, 23298
Research Site
Rochester, Minnesota, 55905
Study site
San Diego, California, 92123
Research Site
Scottsdale, Arizona, 85259
About this study
Official title: A Phase 2a, Randomized, Double-Blind, Placebo Controlled, Dose Ranging, Multicenter Study to Determine the Safety, Tolerance, and Efficacy of Larazotide Acetate (AT-1001) in Celiac Disease Subjects During Gluten Challenge.
This study was run to determine the safety, tolerance, and efficacy of multiple doses of larazotide acetate in subjects with celiac disease following a gluten challenge.
Read the detailed description
CLIN1001-004 was a randomized, double-blind, placebo controlled, dose-ranging, 7-arm, multicenter study with a gluten challenge. The objects were multiple dose safety and tolerance; efficacy (intestinal permeability [change in urinary LAMA ratio] and disease signs and symptoms) following gluten challenge.
Following a 21-day screening period, subjects were randomized to one of seven treatments groups: four groups received larazotide acetate (0.25 mg, 1 mg, 4 mg or 8 mg TID) along with an 800 mg gluten challenge, one group received placebo with an 800 mg gluten challenge, a safety control arm received the highest dose of larazotide acetate (8 mg TID) and gluten placebo and the last group received drug placebo and gluten placebo. The gluten challenge was administered as capsules (800 mg TID) with each main meal for a total of 2.4 g daily. Drug or drug placebo was administered TID 15 minutes prior to each main meal. Subjects received their assigned treatments for two weeks (Day 0 through Day 14) and came to clinic for a follow-up visit one week later (Day 21). Subjects remained on their gluten-free diet for the duration of the study.
- Conditions
- Celiac Disease
- Being tested
- larazotide acetate, Placebo
- Keywords
- larazotide acetate
- Medical subject headings
- Celiac Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
larazotide acetateDrug
Also called AT-1001, INN-202
capsule
PlaceboDrug
capsule
| Study group | Role | What they receive |
|---|---|---|
| Placebo + Gluten | Placebo comparator | placebo TID + gluten 800 mg TID administered orally in capsules Receives: Drug: Placebo |
| Placebo + Gluten placebo | Placebo comparator | placebo TID + gluten placebo TID administered orally in capsules Receives: Drug: Placebo |
| Larazotide acetate 8 mg + Gluten placebo | Other | Safety Control Arm. Larazotide acetate 8 mg TID + gluten placebo TID administered orally in capsules Receives: Drug: larazotide acetate |
| Larazotide acetate 0.25 mg + Gluten | Active comparator | Larazotide acetate 0.25 mg TID + gluten 800 mg TID administered orally in capsules Receives: Drug: larazotide acetate |
| Larazotide acetate 1 mg + Gluten | Active comparator | Larazotide acetate 1 mg TID + gluten 800 mg TID administered orally in capsules Receives: Drug: larazotide acetate |
| Larazotide acetate 4 mg + Gluten | Active comparator | Larazotide acetate 4 mg TID + gluten 800 mg TID administered orally in capsules Receives: Drug: larazotide acetate |
| Larazotide acetate 8 mg + Gluten | Active comparator | Larazotide acetate 8 mg TID + gluten 800 mg TID administered orally in capsules Receives: Drug: larazotide acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
To demonstrate the safety and tolerability of multiple, oral doses of larazotide acetate in celiac disease subjects that maintain a gluten-free diet.
Safety endpoints assessed in this study were adverse events, vital signs, hematology, clinical chemistry, urinalysis and ECG
Measured: Safety measurements were performed at Screening and at Day 0, 7, 14, and 21 ('End of Study'). Any change from baseline value was calculated at each subsequent visit until "End of Study" (Day 21).
To evaluate the efficacy of multiple dose levels of larazotide acetate in preventing intestinal permeability changes induced by gluten challenge
The primary efficacy outcome was the Day 0-to-Day 14 change in urinary LAMA ratio ( a measure of intestinal permeability) as a response to gluten
Measured: On Days 0, 6, 13, and 20 subjects drank a solution of lactulose and mannitol. Subject's urine was collected during the day on Day 0 and overnight prior to subsequent visits and analyzed for LAMA recoveries via standardized methodologies.
Secondary outcomes (8)
Changes in daily and weekly reported health outcomes
Health outcomes were assessed using a daily symptom diary; a weekly PGWBI and a weekly GSRS
Measured: Symptom diary - daily; PGWBI - weekly; GSRS - weekly
Changes in urinary LAMA ratios between Day 0 to Day 7
See Primary Outcome Measure No. 2
Measured: See Primary Outcome Measure No. 2
Changes in urinary lactulose fractional excretion between Day 0 to Day 7 to Day 14
See Primary Outcome Measure No. 2
Measured: See Primary Outcome Measure No. 2
Changes in urinary mannitol fractional excretion between Day 0 to Day 7 to Day 14
See Primary Outcome Measure No. 2
Measured: See Primary Outcome Measure No. 2
Change in urinary nitrite / nitrate levels from Day 0 to Day 14
Nitrite/nitrate levels were assessed for correlation to the measures of intestinal permeability
Measured: Day 0 and Day 14
Change in anti-tTG levels from Screening to Day 21
Changes between screening and Day 21 anti-tTG levels were assessed for correlation to the measures of intestinal permeability
Measured: Screening and Day 21
Change in cell markers and cytokines from PBMCs
Serum cytokine and cell surface marker determinations were assessed for correlation to the measures of intestinal permeability
Measured: Days 0, 7, 14 and 21
Changes in zonulin level
Serum zonulin levels were assessed for correlation to the measures of intestinal permeability
Measured: Days 0, 7, 14 and 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2006 (estimated)
- Study start13 Sep 2006
- Primary completion6 Mar 2007
- Study completion6 Mar 2007
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 Celiac DiseaseStudies 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
- randomized, double-blind, placebo controlled, dose ranging, multicenter
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- 9 Meters Biopharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00362856
- Sponsor's protocol ID
- CLIN1001-004
- Status last verified
- Sep 2017
- First submitted
- 8 Aug 2006
- Last updated
- 12 Sep 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Leffler DA, Kelly CP, Abdallah HZ, Colatrella AM, Harris LA, Leon F, Arterburn LA, Paterson BM, Lan ZH, Murray JA. A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge. Am J Gastroenterol. 2012 Oct;107(10):1554-62. doi: 10.1038/ajg.2012.211. Epub 2012 Jul 24.
PubMed 22825365
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a, Randomized, Double-Blind, Placebo Controlled, Dose Ranging, Multicenter Study to Determine the Safety, Tolerance, and Efficacy of Larazotide Acetate (AT-1001) in Celiac Disease Subjects During Gluten Challenge.
- ClinicalTrials.gov ID
- NCT00362856
- Acronym / sponsor ID
- CLIN1001-004
- Conditions
- Celiac Disease
- Keywords
- larazotide acetate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- 9 Meters Biopharma, Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Sep 2006 (actual)
- Primary completion
- 6 Mar 2007 (actual)
- Study completion
- 6 Mar 2007 (actual)
- First posted
- 10 Aug 2006 (estimated)
- 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.
This study was run to determine the safety, tolerance, and efficacy of multiple doses of larazotide acetate in subjects with celiac disease following a gluten challenge.
Detailed description
CLIN1001-004 was a randomized, double-blind, placebo controlled, dose-ranging, 7-arm, multicenter study with a gluten challenge. The objects were multiple dose safety and tolerance; efficacy (intestinal permeability [change in urinary LAMA ratio] and disease signs and symptoms) following gluten challenge.
Following a 21-day screening period, subjects were randomized to one of seven treatments groups: four groups received larazotide acetate (0.25 mg, 1 mg, 4 mg or 8 mg TID) along with an 800 mg gluten challenge, one group received placebo with an 800 mg gluten challenge, a safety control arm received the highest dose of larazotide acetate (8 mg TID) and gluten placebo and the last group received drug placebo and gluten placebo. The gluten challenge was administered as capsules (800 mg TID) with each main meal for a total of 2.4 g daily. Drug or drug placebo was administered TID 15 minutes prior to each main meal. Subjects received their assigned treatments for two weeks (Day 0 through Day 14) and came to clinic for a follow-up visit one week later (Day 21). Subjects remained on their gluten-free diet for the duration of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 7
- Model description
- randomized, double-blind, placebo controlled, dose ranging, multicenter
| Arm | Type | Receives |
|---|---|---|
| Placebo + Gluten | Placebo comparator | Drug: Placeboplacebo TID + gluten 800 mg TID administered orally in capsules |
| Placebo + Gluten placebo | Placebo comparator | Drug: Placeboplacebo TID + gluten placebo TID administered orally in capsules |
| Larazotide acetate 8 mg + Gluten placebo | Other | Drug: larazotide acetateSafety Control Arm. Larazotide acetate 8 mg TID + gluten placebo TID administered orally in capsules |
| Larazotide acetate 0.25 mg + Gluten | Active comparator | Drug: larazotide acetateLarazotide acetate 0.25 mg TID + gluten 800 mg TID administered orally in capsules |
| Larazotide acetate 1 mg + Gluten | Active comparator | Drug: larazotide acetateLarazotide acetate 1 mg TID + gluten 800 mg TID administered orally in capsules |
| Larazotide acetate 4 mg + Gluten | Active comparator | Drug: larazotide acetateLarazotide acetate 4 mg TID + gluten 800 mg TID administered orally in capsules |
| Larazotide acetate 8 mg + Gluten | Active comparator | Drug: larazotide acetateLarazotide acetate 8 mg TID + gluten 800 mg TID administered orally in capsules |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Must have been diagnosed with celiac disease by biopsy for ≥ 6 months.
- Have a Anti-Tissue Transglutaminase (tTG) ≤ 10 EU as measured by serology.
- Must be on a gluten-free diet for at least the past 6 months.
Key exclusion criteria (4 listed)
- Have any chronic active GI disease other than celiac disease (e.g., IBS, Crohn's, Colitis).
- Have diabetes (Type 1 or Type 2).
- Chronically consumes non-steroidal anti-inflammatory agents ("NSAIDs") or takes proton-pump inhibitors.
- Consuming oral corticosteroids or immune suppressants.
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 |
|---|---|---|
| larazotide acetateAlso: AT-1001, INN-202capsule | Drug | Larazotide acetate 0.25 mg + Gluten, Larazotide acetate 1 mg + Gluten, Larazotide acetate 4 mg + Gluten, Larazotide acetate 8 mg + Gluten, Larazotide acetate 8 mg + Gluten placebo |
| Placebocapsule | Drug | Placebo + Gluten, Placebo + Gluten placebo |
Primary outcome
To demonstrate the safety and tolerability of multiple, oral doses of larazotide acetate in celiac disease subjects that maintain a gluten-free diet.
Time frame: Safety measurements were performed at Screening and at Day 0, 7, 14, and 21 ('End of Study'). Any change from baseline value was calculated at each subsequent visit until "End of Study" (Day 21).
Safety endpoints assessed in this study were adverse events, vital signs, hematology, clinical chemistry, urinalysis and ECG
To evaluate the efficacy of multiple dose levels of larazotide acetate in preventing intestinal permeability changes induced by gluten challenge
Time frame: On Days 0, 6, 13, and 20 subjects drank a solution of lactulose and mannitol. Subject's urine was collected during the day on Day 0 and overnight prior to subsequent visits and analyzed for LAMA recoveries via standardized methodologies.
The primary efficacy outcome was the Day 0-to-Day 14 change in urinary LAMA ratio ( a measure of intestinal permeability) as a response to gluten
8 secondary outcomes
Changes in daily and weekly reported health outcomes
Time frame: Symptom diary - daily; PGWBI - weekly; GSRS - weekly
Changes in urinary LAMA ratios between Day 0 to Day 7
Time frame: See Primary Outcome Measure No. 2
Changes in urinary lactulose fractional excretion between Day 0 to Day 7 to Day 14
Time frame: See Primary Outcome Measure No. 2
Changes in urinary mannitol fractional excretion between Day 0 to Day 7 to Day 14
Time frame: See Primary Outcome Measure No. 2
Change in urinary nitrite / nitrate levels from Day 0 to Day 14
Time frame: Day 0 and Day 14
Change in anti-tTG levels from Screening to Day 21
Time frame: Screening and Day 21
Change in cell markers and cytokines from PBMCs
Time frame: Days 0, 7, 14 and 21
Changes in zonulin level
Time frame: Days 0, 7, 14 and 21
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2017.
- Results publication: PubMed 22825365Leffler DA, Kelly CP, Abdallah HZ, Colatrella AM, Harris LA, Leon F, Arterburn LA, Paterson BM, Lan ZH, Murray JA. A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge. Am J Gastroenterol. 2012 Oct;107(10):1554-62. doi: 10.1038/ajg.2012.211. Epub 2012 Jul 24.
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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.
The record lists no contact. Use the official record to reach the sponsor.
9 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 larazotide acetate in people with Celiac Disease, run by 9 Meters Biopharma, Inc. at 9 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 3 inclusion and 4 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 12 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To demonstrate the safety and tolerability of multiple, oral doses of larazotide acetate in celiac disease subjects that maintain a gluten-free diet. (time frame: Safety measurements were performed at Screening and at Day 0, 7, 14, and 21 ('End of Study'). Any change from baseline value was calculated at each subsequent visit until "End of Study" (Day 21).). The study lists 2 primary outcomes in all. 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 NCT00362856, 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 12 Sep 2017.