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Multiple SclerosisPhase 2NCT03560739

A 12 Week Randomized Open Label Parallel Group Multicenter Study to Evaluate Bioequivalence of 20 mg Subcutaneous Ofatumumab Injected by Pre-filled Syringe or Autoinjector in Adult RMS Patients

A Phase 2 study testing ofatumumab with PRF and ofatumumab with AI in people with Multiple Sclerosis, run by Novartis Pharmaceuticals at 41 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The primary purpose of this study is to demonstrate pharmacokinetic bioequivalence of ofatumumab injected by Pre-filled Syringe (PFS) versus Auto-Injector (AI) devices and thereby establish a bridge between the ongoing Phase 3 program and the to-be-marketed drug-device combinations Read more about this study

Who is it for?
Ages 18 to 55 years
Conditions the study is for
Multiple Sclerosis
What is being tested?
ofatumumab with PRF and ofatumumab with AI
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
284 participants
Where
41 sitesin 9 countries
Study dates
11 Sep 2018to 5 May 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 18 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Diagnosis of multiple sclerosis (MS)
  • Relapsing MS: relapsing-remitting course (RRMS), or Secondary progressive (SPMS) course
  • EDSS score of 0 to 5.5
  • Documentation of at least: 1 relapse during the previous year OR 2 relapses during the previous 2 years prior to Screening OR a positive Gd-enhancing MRI scan during the year prior to randomization.
  • Neurologically stable within 1 month prior to randomization

Who cannot join

  • Patients with primary progressive MS or SPMS without disease activity
  • Disease duration of more than 10 years in patients with EDSS score of 2 or less
  • Patients with an active chronic disease of the immune system other than MS
  • Patients with active systemic bacterial, viral or fungal infections, or known to have AIDS or to test positive for HIV antibody at Screening
  • Patients with neurological findings consistent with Progressive Multifocal Leukoencephalopathy (PML), or confirmed PML

Trial locations and contacts

41 sites in 9 countries.

41 sites in 9 countries

United States13 sites

  • Novartis Investigative Site

    Aurora, Colorado, 80045

  • Novartis Investigative Site

    Basalt, Colorado, 81621

  • Novartis Investigative Site

    Boulder, Colorado, 80301

  • Novartis Investigative Site

    Fullerton, California, 92835

  • Novartis Investigative Site

    Indianapolis, Indiana, 46256

  • Novartis Investigative Site

    Knoxville, Tennessee, 37922

  • Novartis Investigative Site

    Miami, Florida, 33136

  • Novartis Investigative Site

    Ozark, Missouri, 65721

  • Novartis Investigative Site

    Round Rock, Texas, 78681

  • Novartis Investigative Site

    Sherman, Texas, 75092

  • Novartis Investigative Site

    Tampa, Florida, 33609

  • Novartis Investigative Site

    Tampa, Florida, 33612

  • Novartis Investigative Site

    West Palm Beach, Florida, 33407

Other trials in United States

Russia6 sites

  • Novartis Investigative Site

    Kazan', 420021

  • Novartis Investigative Site

    Krasnoyarsk, 660049

  • Novartis Investigative Site

    Moscow, 127015

  • Novartis Investigative Site

    Novosibirsk, 630007

  • Novartis Investigative Site

    Saint Petersburg, 190000

  • Novartis Investigative Site

    Saint Petersburg, 197022

Other trials in Russia

Czechia5 sites

  • Novartis Investigative Site

    Brno, Czech Republic, 656 91

  • Novartis Investigative Site

    Havířov, Czech Republic, 736 01

  • Novartis Investigative Site

    Hradec Králové, CZE, 500 05

  • Novartis Investigative Site

    Pardubice, 532 03

  • Novartis Investigative Site

    Teplice, Czech Republic, 415 01

Other trials in Czechia

Bulgaria4 sites

  • Novartis Investigative Site

    Sofia, 1113

  • Novartis Investigative Site

    Sofia, 1309

  • Novartis Investigative Site

    Sofia, 1413

  • Novartis Investigative Site

    Sofia, 1431

Other trials in Bulgaria

Spain4 sites

  • Novartis Investigative Site

    Barcelona, Catalonia, 08035

  • Novartis Investigative Site

    Castilleja de la Cuesta, Sevilla, 41950

  • Novartis Investigative Site

    El Palmar, Murcia, 30120

  • Novartis Investigative Site

    Pozuelo de Alarcón, Madrid, 28223

Other trials in Spain

Latvia3 sites

  • Novartis Investigative Site

    Riga, LV, LV-1005

  • Novartis Investigative Site

    Riga, LV 1002

  • Novartis Investigative Site

    Riga, LV-1038

Other trials in Latvia

Austria2 sites

  • Novartis Investigative Site

    Vienna, 1010

  • Novartis Investigative Site

    Vienna, 1090

Other trials in Austria

Estonia2 sites

  • Novartis Investigative Site

    Tallinn, 10617

  • Novartis Investigative Site

    Tartu, 51014

Other trials in Estonia

Lithuania2 sites

  • Novartis Investigative Site

    Kaunas, LTU, LT 50161

  • Novartis Investigative Site

    Vilnius, LT-08661

Other trials in Lithuania

About this study

The primary purpose of this study is to demonstrate pharmacokinetic bioequivalence of ofatumumab injected by Pre-filled Syringe (PFS) versus Auto-Injector (AI) devices and thereby establish a bridge between the ongoing Phase 3 program and the to-be-marketed drug-device combinations

Read the detailed description

Characterization of the pharmacokinetics of ofatumumab administered via the PFS used inclinical trials and the to-be-marketed autoinjector at the clinical dose of 20 mg will be conducted after an initial depletion of CD20 positive B-cells. Comparing the ofatumumab pharmacokinetics between the two drug-device combinations only after the induction period is expected to reduce initial high variability due to target-mediated clearance. This ensures a more stable baseline for PK comparison in a parallel group study design and reflects the clinical situation where systemic concentrations are at steady-state. In order to justify the resulting longterm B-cell depletion, a PK comparability study between the PFS and the AI can only be conducted in MS patients rather than in healthy subjects to balance the risk/benefit and to obtain PK data from the relevant patient population. In order for patients to obtain a clinical benefit from participation in the study, continued treatment with ofatumumab will be offered to all eligible patients through enrollment into the open-label Phase 3 extension study (separate protocol, COMB157G2399).

A secondary objective of the study is to characterize the pharmacokinetics following subcutaneous administration of ofatumumab to either the abdominal region or the thigh which are two injections sites allowed in the Phase 3 study and planned for inclusion in the label. Another secondary objective is assessment of immunogenicity during the 12 weeks duration of the study addressing potential differences in ofatumumab anti-drug antibody formation between the PFS and AI devices as well as between abdomen and thigh injection sites.

This was a randomized, open-label, multi-center, parallel group 12-week study to evaluate the pharmacokinetic bioequivalence of ofatumumab injected by pre-filled syringe (PFS) or autoinjector (AI) devices. The study design included four parallel groups of relapsing multiple sclerosis (RMS) patients. Assessment of the primary and secondary endpoints was based on data collected through the dosing interval between Week 8 and Week 12 where approximate steady-state pharmacokinetics was anticipated.

All patients received open-label ofatumumab 20 mg sc every 4 weeks (after an initial loading regimen of three weekly 20 mg doses in the first 14 days) and were randomized (5:5:1:1) into 4 groups dependent on device and location of injection. Randomization was not blinded. Groups: 1: PFS, abdomen, 2: AI, abdomen 3: PFS, thigh 4: AI, thigh.

The study had 3 Parts. Part 1 was a 30 day screening period. Part 2 was a treatment period which had an induction period of 4 weeks, followed by 4 weeks to ensure steady state was reached and a 4 week pharmacokinetics phase for a total of 12 weeks.

Part 3 was a safety follow-up period for patients who completed the study but did not enter the extension study and patients who prematurely discontinued the study. This period was 9 months for patients who had repleted their B-cells (back to baseline value). For patients who had not repleted their B-cells, 3 month assessments were done until their B-cells were repleted or patients had initiated other disease modifying/immunosuppressive thereapy.

Being tested
ofatumumab with PRF, ofatumumab with AI
Keywords
Relapsing Multiple Sclerosis, Relapsing-remitting Multiple Sclerosis, Secondary progressive Multiple Sclerosis, Bioequivalence, Pharmacokinetics, Neurofilament light chain, Pre-filled Syringe, Auto-injector, adult, AI, PFS, OMB157
Medical subject headings
Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Chronic Progressive, Charcot-Marie-Tooth disease, Type 1F

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ofatumumab with PRFCombination product

    ofatumumab 20 mg subcutanious injection administered with pre-filled syringe (PRF)

  • ofatumumab with AICombination product

    ofatumumab 20 mg subcutaneous injection administered with autoinjector (AI)

Study groups in NCT03560739
Study groupRoleWhat they receive
OMB 20mg PFS abdomenOtherofatumumab 20 mg subcutaneous (sc.) injection with pre-filled syringes (PFS) administrated on abdomen
Receives: Combination Product: ofatumumab with PRF
OMB 20mg AI abdomenOtherofatumumab 20 mg subcutaneous (sc.) injection with autoinjector (AI) administrated on abdomen
Receives: Combination Product: ofatumumab with AI
OMB 20mg PFS thighOtherofatumumab 20 mg subcutaneous (sc.) injection with pre-filled syringes (PFS) administrated on thigh
Receives: Combination Product: ofatumumab with PRF
OMB 20mg AI thighOtherofatumumab 20 mg subcutaneous (sc.) injection with autoinjector (AI) administrated on thigh
Receives: Combination Product: ofatumumab with AI

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Bioequivalence of 20 mg Ofatumumab Injected by Pre-filled Syringe (PFS) vs Autoinjector (AI) to Abdomen as Measured by AUCtau

    Bioequivalence of AUCtau ) will be measured over the time period of Week 8 to Week 12 dosing interval comparing the pre-filled syringe (PFS) and autoinjector (AI) devices both administered to the abdomen. Bioequivalence established if both measures meet the corresponding criterion specified by the reference-scaled average bioequivalence (RSABE) approach

    Measured: Week 8 to Week 12 dosing interval

  2. Bioequivalence of 20 mg Ofatumumab Injected by Pre-filled Syringe (PFS) vs Autoinjector (AI) to Abdomen as Measured by Cmax

    Bioequivalence of Cmax will be measured over the time period of Week 8 to Week 12 dosing interval comparing the pre-filled syringe (PFS) and autoinjector (AI) devices both administered to the abdomen. Bioequivalence established if both measures meet the corresponding criterion specified by the reference-scaled average bioequivalence (RSABE) approach

    Measured: Week 8 to Week 12 dosing interval

Secondary outcomes (4)

  1. Pharmacokinetics of the Study Drug as Measured by AUCtau for PFS and AI Devices When Administered to Abdomen or Thigh

    Pharmacokinetics following subcutaneous administration of ofatumumab to either the abdominal region or the thigh as measured by the area under the concentration-time curve over the Week 8 - Week 12 dosing interval (AUCtau)

    Measured: Week 8 to Week 12 dosing interval

  2. Pharmacokinetics of the Study Drug as Measured by Cmax for PFS and AI Devices When Administered to Abdomen or Thigh

    Pharmacokinetics following subcutaneous administration of ofatumumab to either the abdominal region or the thigh as measured by the maximum concentration (Cmax)

    Measured: Week 8 to Week 12 dosing interval

  3. Plasma Concentrations of the Study Drug for PFS and AI Devices When Administered to Abdomen or Thigh

    Plasma concentrations following subcutaneous administration of ofatumumab via PFS or AI to either the abdominal region or the thigh

    Measured: Days 4, 7, 14, 28, 42, 56, 57, 59, 63, 70, 77, 84

  4. Percentage of Patients With Anti-ofatumumab Antibodies

    Anti-drug antibodies (ADA) were assessed to evaluate the immunogenicity potential of ofatumumab. Samples for ADA assessment were taken prior to dosing at the visit. Samples were analyzed as per laboratory's SOPs by a Meso Scale Discovery (MSD) electrochemiluminescense assay. All samples confirmed to be positive for the presence of anti-ofatumumab antibodies were assessed to evaluate their ability to neutralize the ofatumumab biologic effect.

    Measured: Baseline, Week 4, 8, 12 and Overall

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jun 2018
  2. Study start11 Sep 2018
  3. Primary completion26 Aug 2019
  4. Study completion5 May 2020

Resources

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
To address the primary objective of testing bioequivalence at dosing interval after Week 8 between Pre-filled Syringe (PFS) and Auto-Injector (AI), the primary analysis involves the two groups (PFS (abdomen) and AI (abdomen)). Further the pharmacokinetcs of ofatumumab will be compared between using the thigh or abdomen for injections.
Masking
None (open label)
Enrolment
284 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03560739
Sponsor's protocol ID
COMB157G2102
Status last verified
Oct 2021
First submitted
15 May 2018
Last updated
8 Oct 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Publications

  • Bar-Or A, Montalban X, Hu X, Kropshofer H, Kukkaro P, Coello N, Ludwig I, Willi R, Zalesak M, Ramanathan K, Kieseier BC, Haring DA, Bagger M, Fox E. Serum Neurofilament Light Trajectories and Their Relation to Subclinical Radiological Disease Activity in Relapsing Multiple Sclerosis Patients in the APLIOS Trial. Neurol Ther. 2023 Feb;12(1):303-317. doi: 10.1007/s40120-022-00427-8. Epub 2022 Dec 19.

    PubMed 36534274

  • Jones B, Li B, Bagger M, Goodyear A, Ludwig I. Statistical methodology for highly variable compounds: A novel design approach for the ofatumumab Phase 2 bioequivalence study. Pharm Stat. 2022 Nov;21(6):1357-1365. doi: 10.1002/pst.2233. Epub 2022 May 23.

    PubMed 35604539

  • Bar-Or A, Wiendl H, Montalban X, Alvarez E, Davydovskaya M, Delgado SR, Evdoshenko EP, Giedraitiene N, Gross-Paju K, Haldre S, Herrman CE, Izquierdo G, Karelis G, Leutmezer F, Mares M, Meca-Lallana JE, Mickeviciene D, Nicholas J, Robertson DS, Sazonov DV, Sharlin K, Sundaram B, Totolyan N, Vachova M, Valis M, Bagger M, Haring DA, Ludwig I, Willi R, Zalesak M, Su W, Merschhemke M, Fox EJ. Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study. Mult Scler. 2022 May;28(6):910-924. doi: 10.1177/13524585211044479. Epub 2021 Oct 4.

    PubMed 34605319

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ofatumumab with PRF and ofatumumab with AI in people with Multiple Sclerosis, run by Novartis Pharmaceuticals at 41 sites in 9 countries.

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 5 inclusion and 5 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 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in United States, Russia, Czechia, Bulgaria, Spain and 4 more countries. 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?

Yes. Results are posted in the registry (first posted 9 Oct 2020). 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?

Bioequivalence of 20 mg Ofatumumab Injected by Pre-filled Syringe (PFS) vs Autoinjector (AI) to Abdomen as Measured by AUCtau (time frame: Week 8 to Week 12 dosing interval). 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 NCT03560739, which also lists 3 linked publications.

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 Oct 2021.

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