Drug-specific AntibodiesPhase 3NCT01959334
Evaluate the Immunogenicity of a Novel Glucagon Formulation
A Phase 3 study testing Nasal Glucagon (NG) and Glucagon IM in people with Drug-specific Antibodies and Diabetes Mellitus, run by Eli Lilly and Company at 1 site in Canada.
Trial summary
This study provides information on immunogenicity of Nasal Glucagon (AMG504-1) with regards to the potential development of treatment-emergent anti-glucagon antibodies. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Drug-specific Antibodies, Diabetes Mellitus
- What is being tested?
- Nasal Glucagon (NG) and Glucagon IM
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2013to Dec 2013
- Phase
- Phase 3
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Availability for the entire study period
- Motivated volunteer and absence of intellectual problems likely to limit the validity of consent to participate in the study or the compliance with protocol requirements; ability to cooperate adequately; ability to understand and observe the instructions of the physician or designee
- Male or female patient with a history of Type 1 or Type 2 diabetes of at least 2 years duration
- A female volunteer must meet one of the following criteria:
- Participant is of childbearing potential and agrees to use one of the accepted contraceptive regimens throughout the entire duration of the study (from the screening visit until study completion). Additionally, if the participant is using systemic contraceptives, she must use an additional form of acceptable contraception. An acceptable method of contraception includes one of the following:
- Abstinence from heterosexual intercourse
Show all 17Show fewer
- Systemic contraceptives (birth control pills, injectable/implant /insertable hormonal birth control products, transdermal patch)
- Intrauterine device (with and without hormones)
- Condom with spermicide
- or
- Participant is of non-childbearing potential, defined as surgically sterile (i.e. has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or in a menopausal state (at least 1 year without menses)
- Volunteer aged of at least 18 years but not older than 70 years
- Volunteer with a BMI greater than or equal to 18.50 and below 35.00 kg/m2
- Light-, non- or ex-smokers. A light smoker is defined as someone smoking 10 cigarettes or less per day for at least 3 months before day 1 of this study. An ex- smoker is defined as someone who completely stopped smoking for at least 6 months before day 1 of this study
- In good general health with no conditions that could influence the outcome of the trial, and in the judgment of the Investigator is a good candidate for the study based on review of available medical history, physical examination and clinical laboratory evaluations
- Willingness to adhere to the protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the volunteer
- The informed consent form must be signed by all volunteers, prior to their participation in the study.
Who cannot join
- Females who are pregnant, actively attempting to get pregnant, or are lactating
- History of significant hypersensitivity to glucagon or any related products as well as severe hypersensitivity reactions (such as angioedema) to any drugs
- Presence of significant gastrointestinal, liver or kidney disease, or any other conditions which in the judgment of the Investigator could interfere with the absorption, distribution, metabolism or excretion of drugs, or could potentiate or predispose to undesired effects
- Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases
- Known presence of rare hereditary problems of galactose and /or lactose intolerance
- Known presence or history of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma (i.e. insulin secreting pancreas tumor)
Show all 20Show fewer
- Presence of clinically significant findings on nasal examination or bilateral anterior rhinoscopy, such as structural abnormalities, nasal polyps, marked septal deviation, nasal tumors
- Nasal surgery in the previous 28 days before Day 1 of this study
- Use of a systemic beta-blocker drug, indomethacin, warfarin or anticholinergic drugs in the previous 28 days before Day 1 of this study
- Use of an immunomodulator medication (including steroids, glucocorticoids, tacrolimus, etc.) in the 28 days before day 1 of this study
- Any other concomitant maintenance therapy that would influence the outcome of the trial or compromise the safety of the patient, at the discretion of the Investigator and the Sponsor, in the previous 28 days before day 1 of this study
- Significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
- Any clinically significant illness in the previous 28 days before day 1 of this study
- Any history of tuberculosis and/or prophylaxis for tuberculosis
- Positive urine screening of alcohol and/or drugs of abuse
- Females who are pregnant according to a positive pregnancy test
- Concurrent participation or intention of participating in another clinical trial during this study
- Volunteers who took an Investigational Product (in another clinical trial) or donated 50 mL or more of blood in the previous 28 days before day 1 of this study
- Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the previous 56 days before day 1 of this study
- No participants will be allowed to enroll in this study more than once (i.e. if the study is conducted with more than 1 group).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single Center, Randomized, Parallel Safety Study To Evaluate The Immunogenicity Of A Novel Glucagon Formulation Compared To Commercially Available Glucagon Administered By Intramuscular Injection In Adults With Type 1 OR Type 2 Diabetes
This study provides information on immunogenicity of Nasal Glucagon (AMG504-1) with regards to the potential development of treatment-emergent anti-glucagon antibodies.
Read the detailed description
This study is a single center, randomized, laboratory-blinded, three periods, parallel design study.
The main objective of this study is to evaluate the immunogenicity of repeated single doses of glucagon following nasal and intramuscular (IM) administration in adults with Type 1 or Type 2 diabetes (T1D or T2D). The secondary objective is to evaluate the safety and tolerability of glucagon following NG and IM administration in adults with T1D or T2D.
A single dose of glucagon was administered in the morning after a 10-hour overnight fast, either by intranasal or intramuscular route, on 3 occasions. Each drug administration was separated by at least seven calendar days. Patients were randomized in a 2:1 ratio (NG:IMG) to receive NG or IMG at each of the 3 periods.
Blood samples were collected for measurement of anti-glucagon antibodies at screening visit, prior to dosing at Period 3, and at the post-study visit (approximately 4 weeks after the last glucagon administration).
- Conditions
- Drug-specific Antibodies, Diabetes Mellitus
- Being tested
- Nasal Glucagon (NG), Glucagon IM
- Keywords
- Diabetes Mellitus, Hypoglycemia, Glucagon, Anti-glucagon Antibody, Immunogenicity
- Medical subject headings
- Diabetes Mellitus, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nasal Glucagon (NG)Drug
Also called Nasal Glucagon, AMG504-1 Dry-Mist Intranasal Glucagon, LY900018
Glucagon IMDrug
Also called GlucaGen® HypoKit
| Study group | Role | What they receive |
|---|---|---|
| Glucagon IM | Active comparator | Glucagon dose of 1 milligram (mg) administered intramuscularly (IM). Receives: Drug: Glucagon IM |
| Nasal Glucagon (NG | Experimental | Nasal Glucagon (NG) doses of 3 mg administered intra-nasally. Receives: Drug: Nasal Glucagon (NG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Treatment-emergent Anti-Drug Antibody (ADA)
Glucagon anti-drug antibodies (ADA) were assessed at baseline through study completion. Percentage of participants (Pts) with ADA=(number of Pts with treatment-emergent ADA/number of Pts assessed)*100. Treatment-Emergent ADA includes treatment-induced ADA and treatment boosted ADA. Treatment-induced is defined as participants with 'Not Detected' ADA at baseline (drug-naive) and at least one post-baseline ADA 'Detected' sample with a corresponding titer that is one 2-fold dilution higher than the MRD (minimal required dilution) of the assay. For the nasal glucagon Tier 1-3 ADA screening assay, the MRD is 1:20. Treatment-boosted is defined as Patient with ADA 'Detected' at baseline (drug-naive) and at least one post-baseline ADA 'Detected' sample with a corresponding titer that is at least (>or=) 4-fold higher than the baseline titer.
Measured: Baseline through study completion (up to 10 weeks)
Percentage of Participants With Neutralizing Antibodies
Measured: Baseline through study completion (up to 10 weeks)
Number of Participants With At Least One Adverse Event
Safety parameters assessed included the occurrence of adverse events, the measurement of clinical laboratory parameters; vital signs, ECGs, physical examination, blood glucose, and examination of the injection site (following the IM administration). An AE was defined as any untoward medical occurrence in a clinical investigation subject administered the investigational product and which did not necessarily have a causal relationship with this treatment
A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Measured: First dose of study drug through the post-study completion (up to 10 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2013 (estimated)
- Study startSep 2013
- Primary completionDec 2013
- Study completionDec 2013
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 Drug-specific AntibodiesStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe 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 3
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Locemia Solutions ULC
- Responsible party
- Sponsor
- Investigators
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01959334
- Sponsor's protocol ID
- 16426
- Other IDs
- I8R-MC-IGBF, AMG105
- Status last verified
- Apr 2016
- First submitted
- 5 Oct 2013
- Last updated
- 6 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com. This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Center, Randomized, Parallel Safety Study To Evaluate The Immunogenicity Of A Novel Glucagon Formulation Compared To Commercially Available Glucagon Administered By Intramuscular Injection In Adults With Type 1 OR Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT01959334
- Acronym / sponsor ID
- 16426
- Conditions
- Drug-specific Antibodies, Diabetes Mellitus
- Keywords
- Diabetes Mellitus, Hypoglycemia, Glucagon, Anti-glucagon Antibody, Immunogenicity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Collaborators
- Locemia Solutions ULC
- Study start
- Sep 2013
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 10 Oct 2013 (estimated)
- Results
- Posted 6 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study provides information on immunogenicity of Nasal Glucagon (AMG504-1) with regards to the potential development of treatment-emergent anti-glucagon antibodies.
Detailed description
This study is a single center, randomized, laboratory-blinded, three periods, parallel design study.
The main objective of this study is to evaluate the immunogenicity of repeated single doses of glucagon following nasal and intramuscular (IM) administration in adults with Type 1 or Type 2 diabetes (T1D or T2D). The secondary objective is to evaluate the safety and tolerability of glucagon following NG and IM administration in adults with T1D or T2D.
A single dose of glucagon was administered in the morning after a 10-hour overnight fast, either by intranasal or intramuscular route, on 3 occasions. Each drug administration was separated by at least seven calendar days. Patients were randomized in a 2:1 ratio (NG:IMG) to receive NG or IMG at each of the 3 periods.
Blood samples were collected for measurement of anti-glucagon antibodies at screening visit, prior to dosing at Period 3, and at the post-study visit (approximately 4 weeks after the last glucagon administration).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Glucagon IM | Active comparator | Drug: Glucagon IMGlucagon dose of 1 milligram (mg) administered intramuscularly (IM). |
| Nasal Glucagon (NG | Experimental | Drug: Nasal Glucagon (NG)Nasal Glucagon (NG) doses of 3 mg administered intra-nasally. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Availability for the entire study period
- Motivated volunteer and absence of intellectual problems likely to limit the validity of consent to participate in the study or the compliance with protocol requirements; ability to cooperate adequately; ability to understand and observe the instructions of the physician or designee
- Male or female patient with a history of Type 1 or Type 2 diabetes of at least 2 years duration
- A female volunteer must meet one of the following criteria:
- or
Key exclusion criteria (20 listed)
- Females who are pregnant, actively attempting to get pregnant, or are lactating
- History of significant hypersensitivity to glucagon or any related products as well as severe hypersensitivity reactions (such as angioedema) to any drugs
- Presence of significant gastrointestinal, liver or kidney disease, or any other conditions which in the judgment of the Investigator could interfere with the absorption, distribution, metabolism or excretion of drugs, or could potentiate or predispose to undesired effects
- Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases
- Known presence of rare hereditary problems of galactose and /or lactose intolerance
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 |
|---|---|---|
| Nasal Glucagon (NG)Also: Nasal Glucagon, AMG504-1 Dry-Mist Intranasal Glucagon, LY900018 | Drug | Nasal Glucagon (NG |
| Glucagon IMAlso: GlucaGen® HypoKit | Drug | Glucagon IM |
Primary outcome
Percentage of Participants With Treatment-emergent Anti-Drug Antibody (ADA)
Time frame: Baseline through study completion (up to 10 weeks)
Glucagon anti-drug antibodies (ADA) were assessed at baseline through study completion. Percentage of participants (Pts) with ADA=(number of Pts with treatment-emergent ADA/number of Pts assessed)*100. Treatment-Emergent ADA includes treatment-induced ADA and treatment boosted ADA. Treatment-induced is defined as participants with 'Not Detected' ADA at baseline (drug-naive) and at least one post-baseline ADA 'Detected' sample with a corresponding titer that is one 2-fold dilution higher than the MRD (minimal required dilution) of the assay. For the nasal glucagon Tier 1-3 ADA screening assay, the MRD is 1:20. Treatment-boosted is defined as Patient with ADA 'Detected' at baseline (drug-naive) and at least one post-baseline ADA 'Detected' sample with a corresponding titer that is at least (>or=) 4-fold higher than the baseline titer.
Percentage of Participants With Neutralizing Antibodies
Time frame: Baseline through study completion (up to 10 weeks)
Number of Participants With At Least One Adverse Event
Time frame: First dose of study drug through the post-study completion (up to 10 weeks)
Safety parameters assessed included the occurrence of adverse events, the measurement of clinical laboratory parameters; vital signs, ECGs, physical examination, blood glucose, and examination of the injection site (following the IM administration). An AE was defined as any untoward medical occurrence in a clinical investigation subject administered the investigational product and which did not necessarily have a causal relationship with this treatment A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com. This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.
Related trials for Drug-specific Antibodies
Active, not recruitingPhase 1
ARX517/JNJ-95298177 as Monotherapy or Combination Therapy in Subjects With Metastatic Prostate Cancer
Metastatic Prostate Cancer
RecruitingPhase 1
A Study of JNJ-78278343 in Combination With JNJ-95298177 for Treatment of Prostate Cancer
Prostatic Neoplasms
Not yet recruitingPhase 1/2
VBC117First-in-Human Trial of VBC117 in Participants With Advanced Malignant Solid Tumors
Advanced Solid Tumors
RecruitingPhase 1/2
First-in-Human Trial of VBC101 in Participants With Advanced Solid Tumor Malignancies
Participants With Advanced Solid Tumor Malignancies
RecruitingPhase 1/2
First-in-Human Trial of VBC108 in Participants With Advanced Malignant Solid Tumors
Advanced Solid Tumors
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.
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) study director
Eli Lilly and Company
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nasal Glucagon (NG) and Glucagon IM in people with Drug-specific Antibodies and Diabetes Mellitus, run by Eli Lilly and Company at 1 site in Canada.
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 17 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: finished, as of the sponsor's last update on 6 Sep 2019. 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 Canada. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 6 Sep 2019). 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?
Percentage of Participants With Treatment-emergent Anti-Drug Antibody (ADA) (time frame: Baseline through study completion (up to 10 weeks)). The study lists 3 primary outcomes in all. 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 6 Sep 2019.